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Cell-free DNA mutational analysis in AITL
SAN FRANCISCO—An exploratory study suggests cell-free DNA from peripheral blood may be a viable alternative to tumor DNA for mutational profiling in angioimmunoblastic T-cell lymphoma (AITL).
Investigators sequenced cell-free DNA and tumor DNA collected from 13 patients with AITL and found that, in 85% of cases, there was concordance between the tumor mutational profile and the cell-free DNA mutational profile.
“The cell-free DNA mutational analysis seems to mirror the mutational analysis of the tumor in the majority of cases,” said Neha Mehta-Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
“This may be particularly interesting when we don’t have very much tumor DNA available for sequencing, as occurs frequently in this patient population.”
Dr Mehta-Shah presented these findings at the 9th Annual T-cell Lymphoma Forum.
She said the primary objective of this study was to evaluate whether somatic mutation analysis of cell-free DNA for IDH2 correlates with tumor mutational profiling for IDH2.
The secondary objective was to evaluate whether somatic mutational analysis of cell-free DNA mirrors the mutational profile of the tumor.
So Dr Mehta-Shah and her colleagues sequenced various samples from 14 patients with AITL (4 who were newly diagnosed and 10 with relapsed disease).
The investigators compared cell-free DNA obtained from peripheral blood samples with genomic DNA obtained from primary tumor biopsies and with DNA from peripheral blood mononuclear cells (for germline comparison). One of the 14 patients didn’t have tumor tissue available, so 13 patients were included in the analysis.
The team performed targeted next-generation sequencing using Memorial Sloan Kettering Cancer Center’s IMPACT platform, which sequences 410 genes known to be recurrently mutated in cancer.
The investigators observed concordance between the tumor mutational profile and the cell-free DNA profile in 85% of cases (11/13).
Identical alterations in TET2, RHOA, IDH2, DNMT3A, and ROS1 were detected in cell-free DNA from peripheral blood and tumor genomic DNA, with a similar variant allele frequency.
On the other hand, mutational analysis of cell-free DNA obtained from urine samples from 2 of the patients did not correlate with somatic mutations from tumor DNA.
This research also revealed that some samples had multiple mutations in TET2, which are indicative of subclonal populations.
And sequential samples from 2 patients, collected at the start of salvage therapy and at subsequent relapse, showed the disappearance of mutations in RHOA, TET2, and IDH2. This observation has been attributed to clonal evolution and/or changes in overall disease burden. 
SAN FRANCISCO—An exploratory study suggests cell-free DNA from peripheral blood may be a viable alternative to tumor DNA for mutational profiling in angioimmunoblastic T-cell lymphoma (AITL).
Investigators sequenced cell-free DNA and tumor DNA collected from 13 patients with AITL and found that, in 85% of cases, there was concordance between the tumor mutational profile and the cell-free DNA mutational profile.
“The cell-free DNA mutational analysis seems to mirror the mutational analysis of the tumor in the majority of cases,” said Neha Mehta-Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
“This may be particularly interesting when we don’t have very much tumor DNA available for sequencing, as occurs frequently in this patient population.”
Dr Mehta-Shah presented these findings at the 9th Annual T-cell Lymphoma Forum.
She said the primary objective of this study was to evaluate whether somatic mutation analysis of cell-free DNA for IDH2 correlates with tumor mutational profiling for IDH2.
The secondary objective was to evaluate whether somatic mutational analysis of cell-free DNA mirrors the mutational profile of the tumor.
So Dr Mehta-Shah and her colleagues sequenced various samples from 14 patients with AITL (4 who were newly diagnosed and 10 with relapsed disease).
The investigators compared cell-free DNA obtained from peripheral blood samples with genomic DNA obtained from primary tumor biopsies and with DNA from peripheral blood mononuclear cells (for germline comparison). One of the 14 patients didn’t have tumor tissue available, so 13 patients were included in the analysis.
The team performed targeted next-generation sequencing using Memorial Sloan Kettering Cancer Center’s IMPACT platform, which sequences 410 genes known to be recurrently mutated in cancer.
The investigators observed concordance between the tumor mutational profile and the cell-free DNA profile in 85% of cases (11/13).
Identical alterations in TET2, RHOA, IDH2, DNMT3A, and ROS1 were detected in cell-free DNA from peripheral blood and tumor genomic DNA, with a similar variant allele frequency.
On the other hand, mutational analysis of cell-free DNA obtained from urine samples from 2 of the patients did not correlate with somatic mutations from tumor DNA.
This research also revealed that some samples had multiple mutations in TET2, which are indicative of subclonal populations.
And sequential samples from 2 patients, collected at the start of salvage therapy and at subsequent relapse, showed the disappearance of mutations in RHOA, TET2, and IDH2. This observation has been attributed to clonal evolution and/or changes in overall disease burden.
SAN FRANCISCO—An exploratory study suggests cell-free DNA from peripheral blood may be a viable alternative to tumor DNA for mutational profiling in angioimmunoblastic T-cell lymphoma (AITL).
Investigators sequenced cell-free DNA and tumor DNA collected from 13 patients with AITL and found that, in 85% of cases, there was concordance between the tumor mutational profile and the cell-free DNA mutational profile.
“The cell-free DNA mutational analysis seems to mirror the mutational analysis of the tumor in the majority of cases,” said Neha Mehta-Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
“This may be particularly interesting when we don’t have very much tumor DNA available for sequencing, as occurs frequently in this patient population.”
Dr Mehta-Shah presented these findings at the 9th Annual T-cell Lymphoma Forum.
She said the primary objective of this study was to evaluate whether somatic mutation analysis of cell-free DNA for IDH2 correlates with tumor mutational profiling for IDH2.
The secondary objective was to evaluate whether somatic mutational analysis of cell-free DNA mirrors the mutational profile of the tumor.
So Dr Mehta-Shah and her colleagues sequenced various samples from 14 patients with AITL (4 who were newly diagnosed and 10 with relapsed disease).
The investigators compared cell-free DNA obtained from peripheral blood samples with genomic DNA obtained from primary tumor biopsies and with DNA from peripheral blood mononuclear cells (for germline comparison). One of the 14 patients didn’t have tumor tissue available, so 13 patients were included in the analysis.
The team performed targeted next-generation sequencing using Memorial Sloan Kettering Cancer Center’s IMPACT platform, which sequences 410 genes known to be recurrently mutated in cancer.
The investigators observed concordance between the tumor mutational profile and the cell-free DNA profile in 85% of cases (11/13).
Identical alterations in TET2, RHOA, IDH2, DNMT3A, and ROS1 were detected in cell-free DNA from peripheral blood and tumor genomic DNA, with a similar variant allele frequency.
On the other hand, mutational analysis of cell-free DNA obtained from urine samples from 2 of the patients did not correlate with somatic mutations from tumor DNA.
This research also revealed that some samples had multiple mutations in TET2, which are indicative of subclonal populations.
And sequential samples from 2 patients, collected at the start of salvage therapy and at subsequent relapse, showed the disappearance of mutations in RHOA, TET2, and IDH2. This observation has been attributed to clonal evolution and/or changes in overall disease burden.
Pathogenesis of breast-implant-associated ALCL
SAN FRANCISCO—A small study suggests an abnormal immune response characterized by the production of interleukin-13 (IL-13) underlies the pathogenesis of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).
The immune response appears to be directed toward bacterial antigens on the surface of the breast implants.
Marshall E. Kadin, MD, of Roger Williams Medical Center in Providence, Rhode Island, presented these findings at the 9th Annual T-cell Lymphoma Forum.
Dr Kadin noted that BIA-ALCL is a rare type of CD30+ T-cell ALCL that has been reported in more than 200 women worldwide.
Although a cause-and-effect relationship between breast implants and BIA-ALCL has been suggested, the underlying pathogenesis of this malignancy is unclear.
A bacterial biofilm containing gram-negative bacilli has been detected in breast implants from patients with BIA-ALCL.
Therefore, Dr Kadin and his colleagues hypothesized that an immune response toward the bacterial antigens may mediate the pathogenesis of BIA-ALCL.
The researchers studied 13 clinical samples of breast implant capsules and regional lymph nodes from 4 patients with BIA-ALCL, 7 patients with systemic ALCL, and 1 patient with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS).
Immunohistochemistry was used to determine the presence of IL-13, IL-4, GATA3, and immunoglobulin E (IgE) in these samples.
All clinical samples of anaplastic cells from breast implant capsules tested positive for the presence of IL-13 (13/13). GATA3 was expressed in most anaplastic cell samples (12/13), and IL-4 expression was found in some anaplastic cell samples (6/13). IL-13 and GATA3 expression were observed in some intra-capsular small lymphocytes.
While IL-13 was also detected in BIA-ALCL cell lines, it was not found in 4 of the 7 systemic ALCL cases or the PTCL-NOS case.
Dr Kadin said the lack of IL-13 receptor expression in BIA-ALCL cell lines suggests that IL-13 is not an autocrine growth factor for BIA-ALCL, and its expression is most likely associated with an allergic immune response.
IL-13 is known to induce immunoglobulin class switching in plasma cells to produce IgE. H&E and Giemsa staining of the BIA-ALCL tumor tissue and involved regional lymph nodes revealed IgE and eosinophils on the surface of mast cells and follicular dendritic cells.
Taken together, these data point to an allergic reaction in breast implant capsules of BIA-ALCL.
Dr Kadin was hopeful that these findings could be extrapolated to prevent BIA-ALCL by identifying individuals at higher risk for developing the disease.
The next step for this research is to decipher the role of bacterial antigens in mediating the immune response and whether women who develop BIA-ALCL have a significant increase in other atopic conditions.
SAN FRANCISCO—A small study suggests an abnormal immune response characterized by the production of interleukin-13 (IL-13) underlies the pathogenesis of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).
The immune response appears to be directed toward bacterial antigens on the surface of the breast implants.
Marshall E. Kadin, MD, of Roger Williams Medical Center in Providence, Rhode Island, presented these findings at the 9th Annual T-cell Lymphoma Forum.
Dr Kadin noted that BIA-ALCL is a rare type of CD30+ T-cell ALCL that has been reported in more than 200 women worldwide.
Although a cause-and-effect relationship between breast implants and BIA-ALCL has been suggested, the underlying pathogenesis of this malignancy is unclear.
A bacterial biofilm containing gram-negative bacilli has been detected in breast implants from patients with BIA-ALCL.
Therefore, Dr Kadin and his colleagues hypothesized that an immune response toward the bacterial antigens may mediate the pathogenesis of BIA-ALCL.
The researchers studied 13 clinical samples of breast implant capsules and regional lymph nodes from 4 patients with BIA-ALCL, 7 patients with systemic ALCL, and 1 patient with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS).
Immunohistochemistry was used to determine the presence of IL-13, IL-4, GATA3, and immunoglobulin E (IgE) in these samples.
All clinical samples of anaplastic cells from breast implant capsules tested positive for the presence of IL-13 (13/13). GATA3 was expressed in most anaplastic cell samples (12/13), and IL-4 expression was found in some anaplastic cell samples (6/13). IL-13 and GATA3 expression were observed in some intra-capsular small lymphocytes.
While IL-13 was also detected in BIA-ALCL cell lines, it was not found in 4 of the 7 systemic ALCL cases or the PTCL-NOS case.
Dr Kadin said the lack of IL-13 receptor expression in BIA-ALCL cell lines suggests that IL-13 is not an autocrine growth factor for BIA-ALCL, and its expression is most likely associated with an allergic immune response.
IL-13 is known to induce immunoglobulin class switching in plasma cells to produce IgE. H&E and Giemsa staining of the BIA-ALCL tumor tissue and involved regional lymph nodes revealed IgE and eosinophils on the surface of mast cells and follicular dendritic cells.
Taken together, these data point to an allergic reaction in breast implant capsules of BIA-ALCL.
Dr Kadin was hopeful that these findings could be extrapolated to prevent BIA-ALCL by identifying individuals at higher risk for developing the disease.
The next step for this research is to decipher the role of bacterial antigens in mediating the immune response and whether women who develop BIA-ALCL have a significant increase in other atopic conditions.
SAN FRANCISCO—A small study suggests an abnormal immune response characterized by the production of interleukin-13 (IL-13) underlies the pathogenesis of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).
The immune response appears to be directed toward bacterial antigens on the surface of the breast implants.
Marshall E. Kadin, MD, of Roger Williams Medical Center in Providence, Rhode Island, presented these findings at the 9th Annual T-cell Lymphoma Forum.
Dr Kadin noted that BIA-ALCL is a rare type of CD30+ T-cell ALCL that has been reported in more than 200 women worldwide.
Although a cause-and-effect relationship between breast implants and BIA-ALCL has been suggested, the underlying pathogenesis of this malignancy is unclear.
A bacterial biofilm containing gram-negative bacilli has been detected in breast implants from patients with BIA-ALCL.
Therefore, Dr Kadin and his colleagues hypothesized that an immune response toward the bacterial antigens may mediate the pathogenesis of BIA-ALCL.
The researchers studied 13 clinical samples of breast implant capsules and regional lymph nodes from 4 patients with BIA-ALCL, 7 patients with systemic ALCL, and 1 patient with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS).
Immunohistochemistry was used to determine the presence of IL-13, IL-4, GATA3, and immunoglobulin E (IgE) in these samples.
All clinical samples of anaplastic cells from breast implant capsules tested positive for the presence of IL-13 (13/13). GATA3 was expressed in most anaplastic cell samples (12/13), and IL-4 expression was found in some anaplastic cell samples (6/13). IL-13 and GATA3 expression were observed in some intra-capsular small lymphocytes.
While IL-13 was also detected in BIA-ALCL cell lines, it was not found in 4 of the 7 systemic ALCL cases or the PTCL-NOS case.
Dr Kadin said the lack of IL-13 receptor expression in BIA-ALCL cell lines suggests that IL-13 is not an autocrine growth factor for BIA-ALCL, and its expression is most likely associated with an allergic immune response.
IL-13 is known to induce immunoglobulin class switching in plasma cells to produce IgE. H&E and Giemsa staining of the BIA-ALCL tumor tissue and involved regional lymph nodes revealed IgE and eosinophils on the surface of mast cells and follicular dendritic cells.
Taken together, these data point to an allergic reaction in breast implant capsules of BIA-ALCL.
Dr Kadin was hopeful that these findings could be extrapolated to prevent BIA-ALCL by identifying individuals at higher risk for developing the disease.
The next step for this research is to decipher the role of bacterial antigens in mediating the immune response and whether women who develop BIA-ALCL have a significant increase in other atopic conditions.
Study sheds light on genetic landscape of HSTL
SAN FRANCISCO—Researchers say they have identified new driver genes and oncogenic pathways in hepatosplenic T-cell lymphoma (HSTL).
The team found that SETD2, a known tumor suppressor, was the most frequently silenced gene in HSTL.
The researchers also found evidence suggesting the JAK-STAT and PI3K pathways could be therapeutic targets in HSTL.
Sandeep Dave, MD, of Duke University in Durham, North Carolina, presented these findings at the 9th Annual T-cell Lymphoma Forum. Results from this research were also published in Cancer Discovery.
The researchers collected complete clinical data on 68 HSTL cases, including 20 with normal DNA. The team performed whole-genome sequencing, bioinformatics analysis, and biological characterization of these cases.
“This is the largest group of HSTL cases ever described, and the data implicate new driver genes and oncogenic pathways for the first time in HSTL,” Dr Dave said.
The data revealed that the most commonly mutated group of genes in HSTL are chromatin modifiers (SETD2, INO80, ARID1B, TET3, and SMARCA2) and signaling pathway genes (STAT5B, STAT3, and PIK3CD). Among these, STAT3, PIK3CD, and SETD2 showed the highest proportion of clonal events.
On the other hand, mutations in EZH2, KRAS, and TP53 were less frequently observed.
Common genetic abnormalities in HSTL include copy number alterations in chromosome 7, trisomy 8, loss of 10p, and gain of 1q.
A comparison of the frequencies of recurrently mutated genes in HSTL with other lymphomas demonstrated the genetically distinct profile of HSTL, wherein mutations in SETD2, INO80, TET3, and STAT5B occurred exclusively in HSTL.
SETD2, a histone lysine methyltransferase and a known tumor suppressor, was identified as the most frequently silenced gene in HSTL.
So the researchers investigated the biological effects of SETD2 loss in HSTL cells and a knockout mouse model.
While loss of SETD2 in HSTL cells resulted in increased cell proliferation, in vivo knockdown of SETD2 led to expansion of γ-δ T cells and a reduction in α-β T cells. A majority of HSTLs are known to arise predominantly from γ-δ T cells.
“These results implicate SETD2 in HSTL oncogenesis and T-cell development,” Dr Dave said.
He and his colleagues also found that constitutive activation of the JAK-STAT and PI3K pathways in HSTL cells was associated with increased proliferation, and inhibition of these pathways led to reduced survival of HSTL cells. This suggests that agents targeting these pathways might be effective in treating HSTL.
SAN FRANCISCO—Researchers say they have identified new driver genes and oncogenic pathways in hepatosplenic T-cell lymphoma (HSTL).
The team found that SETD2, a known tumor suppressor, was the most frequently silenced gene in HSTL.
The researchers also found evidence suggesting the JAK-STAT and PI3K pathways could be therapeutic targets in HSTL.
Sandeep Dave, MD, of Duke University in Durham, North Carolina, presented these findings at the 9th Annual T-cell Lymphoma Forum. Results from this research were also published in Cancer Discovery.
The researchers collected complete clinical data on 68 HSTL cases, including 20 with normal DNA. The team performed whole-genome sequencing, bioinformatics analysis, and biological characterization of these cases.
“This is the largest group of HSTL cases ever described, and the data implicate new driver genes and oncogenic pathways for the first time in HSTL,” Dr Dave said.
The data revealed that the most commonly mutated group of genes in HSTL are chromatin modifiers (SETD2, INO80, ARID1B, TET3, and SMARCA2) and signaling pathway genes (STAT5B, STAT3, and PIK3CD). Among these, STAT3, PIK3CD, and SETD2 showed the highest proportion of clonal events.
On the other hand, mutations in EZH2, KRAS, and TP53 were less frequently observed.
Common genetic abnormalities in HSTL include copy number alterations in chromosome 7, trisomy 8, loss of 10p, and gain of 1q.
A comparison of the frequencies of recurrently mutated genes in HSTL with other lymphomas demonstrated the genetically distinct profile of HSTL, wherein mutations in SETD2, INO80, TET3, and STAT5B occurred exclusively in HSTL.
SETD2, a histone lysine methyltransferase and a known tumor suppressor, was identified as the most frequently silenced gene in HSTL.
So the researchers investigated the biological effects of SETD2 loss in HSTL cells and a knockout mouse model.
While loss of SETD2 in HSTL cells resulted in increased cell proliferation, in vivo knockdown of SETD2 led to expansion of γ-δ T cells and a reduction in α-β T cells. A majority of HSTLs are known to arise predominantly from γ-δ T cells.
“These results implicate SETD2 in HSTL oncogenesis and T-cell development,” Dr Dave said.
He and his colleagues also found that constitutive activation of the JAK-STAT and PI3K pathways in HSTL cells was associated with increased proliferation, and inhibition of these pathways led to reduced survival of HSTL cells. This suggests that agents targeting these pathways might be effective in treating HSTL.
SAN FRANCISCO—Researchers say they have identified new driver genes and oncogenic pathways in hepatosplenic T-cell lymphoma (HSTL).
The team found that SETD2, a known tumor suppressor, was the most frequently silenced gene in HSTL.
The researchers also found evidence suggesting the JAK-STAT and PI3K pathways could be therapeutic targets in HSTL.
Sandeep Dave, MD, of Duke University in Durham, North Carolina, presented these findings at the 9th Annual T-cell Lymphoma Forum. Results from this research were also published in Cancer Discovery.
The researchers collected complete clinical data on 68 HSTL cases, including 20 with normal DNA. The team performed whole-genome sequencing, bioinformatics analysis, and biological characterization of these cases.
“This is the largest group of HSTL cases ever described, and the data implicate new driver genes and oncogenic pathways for the first time in HSTL,” Dr Dave said.
The data revealed that the most commonly mutated group of genes in HSTL are chromatin modifiers (SETD2, INO80, ARID1B, TET3, and SMARCA2) and signaling pathway genes (STAT5B, STAT3, and PIK3CD). Among these, STAT3, PIK3CD, and SETD2 showed the highest proportion of clonal events.
On the other hand, mutations in EZH2, KRAS, and TP53 were less frequently observed.
Common genetic abnormalities in HSTL include copy number alterations in chromosome 7, trisomy 8, loss of 10p, and gain of 1q.
A comparison of the frequencies of recurrently mutated genes in HSTL with other lymphomas demonstrated the genetically distinct profile of HSTL, wherein mutations in SETD2, INO80, TET3, and STAT5B occurred exclusively in HSTL.
SETD2, a histone lysine methyltransferase and a known tumor suppressor, was identified as the most frequently silenced gene in HSTL.
So the researchers investigated the biological effects of SETD2 loss in HSTL cells and a knockout mouse model.
While loss of SETD2 in HSTL cells resulted in increased cell proliferation, in vivo knockdown of SETD2 led to expansion of γ-δ T cells and a reduction in α-β T cells. A majority of HSTLs are known to arise predominantly from γ-δ T cells.
“These results implicate SETD2 in HSTL oncogenesis and T-cell development,” Dr Dave said.
He and his colleagues also found that constitutive activation of the JAK-STAT and PI3K pathways in HSTL cells was associated with increased proliferation, and inhibition of these pathways led to reduced survival of HSTL cells. This suggests that agents targeting these pathways might be effective in treating HSTL.
Drug produces high response rates in AITL
Photo by Larry Young
SAN FRANCISCO—Treatment with 5-azacitidine (5-AZA) can produce a high response rate in patients with relapsed/refractory angioimmunoblastic T-cell lymphoma (AITL), according to a small study.
The overall response rate (ORR) among AITL patients was 75%, and the complete response (CR) rate was 42%.
However, this study also included patients with other types of peripheral T-cell lymphoma (PTCL), and most of these patients did not respond to 5-AZA.
Richard Delarue, MD, of Necker University Hospital in Paris, France, presented these results at the 9th Annual T-cell Lymphoma Forum.
Results were also presented at the 2016 ASH Annual Meeting (abstract 4164). Dr Delarue reported receiving honoraria from Celgene.
Patients
The study included 19 patients with relapsed/refractory PTCL. Twelve patients had AITL, 3 had adult T-cell leukemia/lymphoma (ATLL), 2 had PTCL not otherwise specified, 1 had enteropathy-associated T-cell lymphoma, and 1 had transformed mycosis fungoides.
At diagnosis, the median age was 71 (range, 39-85) for AITL patients and 59 (range, 32-83) for the other PTCL patients. Seventy-five percent of AITL patients had an IPI score of 3 to 5 and a PIT score of 3 to 4. Eighty-six percent of the other PTCL patients had an IPI score of 3 to 5, and 57% had a PIT score of 3 to 4.
At the time of 5-AZA treatment, all patients had stage III/IV disease. The AITL patients had received a median of 2 (range, 0-6) prior lines of therapy, and the other PTCL patients had received a median of 3 (range, 0-7).
Two patients did not receive chemotherapy before 5-AZA because of the presence of associated chronic myelomonocytic leukemia (CMML) that required treatment first.
Ninety-two percent of AITL patients had TET2 mutations (n=11), 33% had DNMT3A mutations (n=4), and 0% had IDH2 mutations. One of the non-AITL patients had a TET2 mutation.
Treatment
Patients received a subcutaneous injection of 5-AZA at 75 mg/m² for 7 consecutive days every 28 days until progression or unacceptable toxicity. Six patients also received 4 to 8 infusions of rituximab because of EBV-DNA positivity.
The patients received a median of 3 cycles of 5-AZA. At the time of analysis, 4 patients were still receiving therapy.
The median follow-up was 84 days (range, 19 to 1236).
Toxicity
“Hematological toxicity was as expected with 5-azacitidine,” Dr Delarue said.
However, 2 patients had “unusual” adverse reactions. One patient had grade 2 polyneuropathy, which was considered related to a paraneoplastic syndrome.
The other patient had grade 3 diarrhea related to colitis of unknown origin, and this led to treatment interruption.
There were no treatment-related deaths.
Efficacy
Dr Delarue noted that the ORR was significantly higher in AITL patients than in patients with the other PTCL subtypes (P=0.0198).
The ORR was 53% in the entire cohort (10/19), 75% (9/12) among AITL patients, and 14% among patients with other PTCLs (1/7).
“The only patient with a response in the ‘other PTCL’ group was a patient with HTLV1-associated ATLL . . . , but he relapsed a couple of weeks after the second cycle,” Dr Delarue explained.
Among the AITL patients, the CR rate was 42% (5/12), the partial response rate was 33% (4/12), and the rate of stable disease was 25% (3/12).
Six AITL patients eventually progressed—after 2, 2, 3, 4, 4, and 20 cycles of therapy, respectively.
Two AITL patients are off therapy but remain in CR after 9 and 10 months (5 and 6 cycles of treatment), respectively.
The median progression-free survival for AITL patients was 16 months, and the median overall survival was 17 months.
Dr DeLarue noted that 4 of the AITL patients had CMML, 1 had non-CMML myelodysplastic syndrome, 3 had monocytosis without CMML, and 4 had normal monocyte counts.
He also said that, at present, it’s not possible to correlate the results observed in the AITL patients with their mutational status.
However, he and his colleagues are planning a prospective study of 5-AZA in patients with relapsed/refractory AITL and T follicular helper cell PTCL not otherwise specified. 5-AZA will be compared to investigator’s choice in this study.
Dr DeLarue said this trial will provide an opportunity to use the new oral formulation of 5-AZA (CC-486). And he and his colleagues welcome collaborators.
Photo by Larry Young
SAN FRANCISCO—Treatment with 5-azacitidine (5-AZA) can produce a high response rate in patients with relapsed/refractory angioimmunoblastic T-cell lymphoma (AITL), according to a small study.
The overall response rate (ORR) among AITL patients was 75%, and the complete response (CR) rate was 42%.
However, this study also included patients with other types of peripheral T-cell lymphoma (PTCL), and most of these patients did not respond to 5-AZA.
Richard Delarue, MD, of Necker University Hospital in Paris, France, presented these results at the 9th Annual T-cell Lymphoma Forum.
Results were also presented at the 2016 ASH Annual Meeting (abstract 4164). Dr Delarue reported receiving honoraria from Celgene.
Patients
The study included 19 patients with relapsed/refractory PTCL. Twelve patients had AITL, 3 had adult T-cell leukemia/lymphoma (ATLL), 2 had PTCL not otherwise specified, 1 had enteropathy-associated T-cell lymphoma, and 1 had transformed mycosis fungoides.
At diagnosis, the median age was 71 (range, 39-85) for AITL patients and 59 (range, 32-83) for the other PTCL patients. Seventy-five percent of AITL patients had an IPI score of 3 to 5 and a PIT score of 3 to 4. Eighty-six percent of the other PTCL patients had an IPI score of 3 to 5, and 57% had a PIT score of 3 to 4.
At the time of 5-AZA treatment, all patients had stage III/IV disease. The AITL patients had received a median of 2 (range, 0-6) prior lines of therapy, and the other PTCL patients had received a median of 3 (range, 0-7).
Two patients did not receive chemotherapy before 5-AZA because of the presence of associated chronic myelomonocytic leukemia (CMML) that required treatment first.
Ninety-two percent of AITL patients had TET2 mutations (n=11), 33% had DNMT3A mutations (n=4), and 0% had IDH2 mutations. One of the non-AITL patients had a TET2 mutation.
Treatment
Patients received a subcutaneous injection of 5-AZA at 75 mg/m² for 7 consecutive days every 28 days until progression or unacceptable toxicity. Six patients also received 4 to 8 infusions of rituximab because of EBV-DNA positivity.
The patients received a median of 3 cycles of 5-AZA. At the time of analysis, 4 patients were still receiving therapy.
The median follow-up was 84 days (range, 19 to 1236).
Toxicity
“Hematological toxicity was as expected with 5-azacitidine,” Dr Delarue said.
However, 2 patients had “unusual” adverse reactions. One patient had grade 2 polyneuropathy, which was considered related to a paraneoplastic syndrome.
The other patient had grade 3 diarrhea related to colitis of unknown origin, and this led to treatment interruption.
There were no treatment-related deaths.
Efficacy
Dr Delarue noted that the ORR was significantly higher in AITL patients than in patients with the other PTCL subtypes (P=0.0198).
The ORR was 53% in the entire cohort (10/19), 75% (9/12) among AITL patients, and 14% among patients with other PTCLs (1/7).
“The only patient with a response in the ‘other PTCL’ group was a patient with HTLV1-associated ATLL . . . , but he relapsed a couple of weeks after the second cycle,” Dr Delarue explained.
Among the AITL patients, the CR rate was 42% (5/12), the partial response rate was 33% (4/12), and the rate of stable disease was 25% (3/12).
Six AITL patients eventually progressed—after 2, 2, 3, 4, 4, and 20 cycles of therapy, respectively.
Two AITL patients are off therapy but remain in CR after 9 and 10 months (5 and 6 cycles of treatment), respectively.
The median progression-free survival for AITL patients was 16 months, and the median overall survival was 17 months.
Dr DeLarue noted that 4 of the AITL patients had CMML, 1 had non-CMML myelodysplastic syndrome, 3 had monocytosis without CMML, and 4 had normal monocyte counts.
He also said that, at present, it’s not possible to correlate the results observed in the AITL patients with their mutational status.
However, he and his colleagues are planning a prospective study of 5-AZA in patients with relapsed/refractory AITL and T follicular helper cell PTCL not otherwise specified. 5-AZA will be compared to investigator’s choice in this study.
Dr DeLarue said this trial will provide an opportunity to use the new oral formulation of 5-AZA (CC-486). And he and his colleagues welcome collaborators.
Photo by Larry Young
SAN FRANCISCO—Treatment with 5-azacitidine (5-AZA) can produce a high response rate in patients with relapsed/refractory angioimmunoblastic T-cell lymphoma (AITL), according to a small study.
The overall response rate (ORR) among AITL patients was 75%, and the complete response (CR) rate was 42%.
However, this study also included patients with other types of peripheral T-cell lymphoma (PTCL), and most of these patients did not respond to 5-AZA.
Richard Delarue, MD, of Necker University Hospital in Paris, France, presented these results at the 9th Annual T-cell Lymphoma Forum.
Results were also presented at the 2016 ASH Annual Meeting (abstract 4164). Dr Delarue reported receiving honoraria from Celgene.
Patients
The study included 19 patients with relapsed/refractory PTCL. Twelve patients had AITL, 3 had adult T-cell leukemia/lymphoma (ATLL), 2 had PTCL not otherwise specified, 1 had enteropathy-associated T-cell lymphoma, and 1 had transformed mycosis fungoides.
At diagnosis, the median age was 71 (range, 39-85) for AITL patients and 59 (range, 32-83) for the other PTCL patients. Seventy-five percent of AITL patients had an IPI score of 3 to 5 and a PIT score of 3 to 4. Eighty-six percent of the other PTCL patients had an IPI score of 3 to 5, and 57% had a PIT score of 3 to 4.
At the time of 5-AZA treatment, all patients had stage III/IV disease. The AITL patients had received a median of 2 (range, 0-6) prior lines of therapy, and the other PTCL patients had received a median of 3 (range, 0-7).
Two patients did not receive chemotherapy before 5-AZA because of the presence of associated chronic myelomonocytic leukemia (CMML) that required treatment first.
Ninety-two percent of AITL patients had TET2 mutations (n=11), 33% had DNMT3A mutations (n=4), and 0% had IDH2 mutations. One of the non-AITL patients had a TET2 mutation.
Treatment
Patients received a subcutaneous injection of 5-AZA at 75 mg/m² for 7 consecutive days every 28 days until progression or unacceptable toxicity. Six patients also received 4 to 8 infusions of rituximab because of EBV-DNA positivity.
The patients received a median of 3 cycles of 5-AZA. At the time of analysis, 4 patients were still receiving therapy.
The median follow-up was 84 days (range, 19 to 1236).
Toxicity
“Hematological toxicity was as expected with 5-azacitidine,” Dr Delarue said.
However, 2 patients had “unusual” adverse reactions. One patient had grade 2 polyneuropathy, which was considered related to a paraneoplastic syndrome.
The other patient had grade 3 diarrhea related to colitis of unknown origin, and this led to treatment interruption.
There were no treatment-related deaths.
Efficacy
Dr Delarue noted that the ORR was significantly higher in AITL patients than in patients with the other PTCL subtypes (P=0.0198).
The ORR was 53% in the entire cohort (10/19), 75% (9/12) among AITL patients, and 14% among patients with other PTCLs (1/7).
“The only patient with a response in the ‘other PTCL’ group was a patient with HTLV1-associated ATLL . . . , but he relapsed a couple of weeks after the second cycle,” Dr Delarue explained.
Among the AITL patients, the CR rate was 42% (5/12), the partial response rate was 33% (4/12), and the rate of stable disease was 25% (3/12).
Six AITL patients eventually progressed—after 2, 2, 3, 4, 4, and 20 cycles of therapy, respectively.
Two AITL patients are off therapy but remain in CR after 9 and 10 months (5 and 6 cycles of treatment), respectively.
The median progression-free survival for AITL patients was 16 months, and the median overall survival was 17 months.
Dr DeLarue noted that 4 of the AITL patients had CMML, 1 had non-CMML myelodysplastic syndrome, 3 had monocytosis without CMML, and 4 had normal monocyte counts.
He also said that, at present, it’s not possible to correlate the results observed in the AITL patients with their mutational status.
However, he and his colleagues are planning a prospective study of 5-AZA in patients with relapsed/refractory AITL and T follicular helper cell PTCL not otherwise specified. 5-AZA will be compared to investigator’s choice in this study.
Dr DeLarue said this trial will provide an opportunity to use the new oral formulation of 5-AZA (CC-486). And he and his colleagues welcome collaborators.
OS is worse with refractory vs relapsed PTCL
Photo by Larry Young
SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.
The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.
However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.
Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).
Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.
Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.
Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).
Patients
There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.
The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.
Disease subtypes included:
- PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
- Angioimmunoblastic T-cell lymphoma—22% and 16%
- ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
- ALK+ ALCL—3% and 4%
- Natural killer/T-cell lymphoma, nasal type—9% and 8%
- Enteropathy-associated T-cell lymphoma—5% and 3%
- Hepatosplenic T-cell lymphoma—3% and 5%
- Adult T-cell leukemia/lymphoma—2% and 5%
- Transformed mycosis fungoides—0% and 10%
- “Other”—10% and 9%.
Treatment
Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.
A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)
Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.
Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).
Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).
The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).
Survival
The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).
OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).
There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).
Disease subtype
There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.
For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).
For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).
Treatment intent
There was a significant difference in OS according to the intent of treatment.
Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).
Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).
Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.
Treatment type
In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).
In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).
In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.
“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”
“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”
Photo by Larry Young
SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.
The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.
However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.
Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).
Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.
Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.
Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).
Patients
There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.
The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.
Disease subtypes included:
- PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
- Angioimmunoblastic T-cell lymphoma—22% and 16%
- ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
- ALK+ ALCL—3% and 4%
- Natural killer/T-cell lymphoma, nasal type—9% and 8%
- Enteropathy-associated T-cell lymphoma—5% and 3%
- Hepatosplenic T-cell lymphoma—3% and 5%
- Adult T-cell leukemia/lymphoma—2% and 5%
- Transformed mycosis fungoides—0% and 10%
- “Other”—10% and 9%.
Treatment
Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.
A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)
Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.
Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).
Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).
The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).
Survival
The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).
OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).
There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).
Disease subtype
There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.
For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).
For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).
Treatment intent
There was a significant difference in OS according to the intent of treatment.
Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).
Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).
Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.
Treatment type
In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).
In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).
In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.
“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”
“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”
Photo by Larry Young
SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.
The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.
However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.
Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).
Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.
Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.
Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).
Patients
There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.
The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.
Disease subtypes included:
- PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
- Angioimmunoblastic T-cell lymphoma—22% and 16%
- ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
- ALK+ ALCL—3% and 4%
- Natural killer/T-cell lymphoma, nasal type—9% and 8%
- Enteropathy-associated T-cell lymphoma—5% and 3%
- Hepatosplenic T-cell lymphoma—3% and 5%
- Adult T-cell leukemia/lymphoma—2% and 5%
- Transformed mycosis fungoides—0% and 10%
- “Other”—10% and 9%.
Treatment
Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.
A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)
Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.
Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).
Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).
The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).
Survival
The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).
OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).
There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).
Disease subtype
There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.
For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).
For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).
Treatment intent
There was a significant difference in OS according to the intent of treatment.
Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).
Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).
Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.
Treatment type
In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).
In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).
In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.
“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”
“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”
Regimens seem similarly effective in ENKTL
Photo by Larry Young
SAN FRANCISCO—Interim results of a phase 3 trial suggest 2 treatment regimens may provide comparable efficacy in patients with extranodal natural killer/T-cell lymphoma (ENKTL), though 1 regimen appears more toxic than the other.
In this ongoing trial, investigators are comparing pegaspargase, gemcitabine, oxaliplatin, and thalidomide (P-Gemox+Thal) to pegaspargase, methotrexate, calcium folinate, and dexamethasone (AspaMetDex).
In some patients, either regimen may be followed by extensive involved-field radiotherapy (EIFRT) or autologous hematopoietic stem cell transplant (ASCT).
Thus far, P-Gemox+Thal and AspaMetDex have proven similarly effective for patients with newly diagnosed, stage I/II ENKTL.
And both regimens have produced unsatisfying survival outcomes in patients with advanced or relapsed/refractory ENKTL, according to investigator Huiqiang Huang, MD, of Sun Yat-sen Institute of Hematology in Guangzhou, China.
In addition, P-Gemox+Thal seems to be less toxic, overall, than AspaMetDex.
However, Dr Huang said it is still too early to draw any firm conclusions about these regimens.
He presented results from this trial at the 9th Annual T-cell Lymphoma Forum. Results were previously presented at the 2016 ASH Annual Meeting (abstract 1819).
Dr Huang noted that AspaMetDex and SMILE (dexamethasone, methotrexate, ifosfamide, lL-asparaginase, and etoposide) are frequently administered to patients with ENKTL. And P-Gemox is recommended in the 2016 NCCN guidelines.
“But optimal regimens still have not been fully defined,” he said.
Therefore, he and his colleagues decided to compare AspaMetDex to P-Gemox+Thal in this non-inferiority trial, which has enrolled 110 patients from 12 centers in China.
Treatment
Fifty-six patients have been randomized to receive P-Gemox+Thal. Every 3 weeks, they received pegaspargase at 2000 U/m2 on day 1, gemcitabine at 1000 mg/m2 on days 1 and 8, and oxaliplatin at 130 mg/m2 on days 1 and 8. They also received thalidomide at 100 mg every day for 1 year.
Fifty-four patients have been randomized to receive AspaMetDex. Every 3 weeks, they received pegaspargase at 2000 U/m2 on day 1, methotrexate at 3000 mg/m2 on day 1, calcium folinate at 30 mg every 6 hours until a safe serum methotrexate concentration was reached, and dexamethasone at 40 mg every day on days 1 to 4.
Newly diagnosed patients with stage I/II disease received either regimen as induction for a maximum of 4 cycles. Responders went on to receive EIFRT at 56 Gy in 28 fractions over 4 weeks.
Patients with newly diagnosed, stage III/IV ENKTL or relapsed/refractory ENKTL received either chemotherapy regimen for a maximum of 6 cycles. If they achieved a complete response (CR), these patients could proceed to ASCT.
Stage I/II ENKTL
Of the 63 stage I/II patients, 33 were randomized to P-Gemox+Thal, and 30 received AspaMetDex. In both arms, most patients were male (69.7% and 70%, respectively) and younger than 60 (78.8% and 90%, respectively).
Ninety-seven percent of patients in the P-Gemox+Thal arm had an ECOG status of 0-1, as did 100% of patients in the AspaMetDex arm.
The overall response rate (ORR) was 85.2% in the P-Gemox+Thal arm and 81.5% in the AspaMetDex arm. The CR rate was 59.3% in both arms. The rate of stable disease was 3.7% in the P-Gemox+Thal arm and 11.1% in the AspaMetDex arm.
After EIFRT, the ORR increased to 92.6% in the P-Gemox+Thal arm, and the CR rate increased to 88.8%. In the AspaMetDex arm, the ORR increased to 88.8%, and the CR rate increased to 85.1%.
At a median follow-up of 13.5 months, the 2-year progression-free survival rate was 82.9% in the P-Gemox+Thal arm and 84.5% in the AspaMetDex arm (P=0.791).
The 2-year overall survival rates were 95.0% in the P-Gemox+Thal arm and 75.8% in the AspaMetDex arm (P=0.089).
Advanced, rel/ref ENKTL
Of the 47 patients with stage III/IV or relapsed/refractory ENKTL, 24 were randomized to P-Gemox+Thal, and 23 to AspaMetDex. In both arms, most patients were male (75% and 87%, respectively) and younger than 60 (95.8% and 91.3%, respectively).
ECOG status was 0 for 62.5% of patients in the P-Gemox+Thal arm and 73.9% of those in the AspaMetDex arm. ECOG status was 1 for 33.3% and 17.4%, respectively.
The ORR was 86.3% in the P-Gemox+Thal arm and 70% in the AspaMetDex arm. The CR rate was 50% in both arms.
The partial response rate was 36.3% in the P-Gemox+Thal arm and 20% in the AspaMetDex arm. And the rate of stable disease was 13.6% and 15%, respectively.
Three patients in each treatment arm went on to ASCT after CR. A total of 3 patients relapsed within 6 months of ASCT—2 in the P-Gemox+Thal arm and 1 in the AspaMetDex arm. Two patients died of disease progression.
At a median follow-up of 14.5 months, the 2-year progression-free survival was 12.2 months in the P-Gemox+Thal arm and 7.6 months in the AspaMetDex arm (P=0.365).
The 2-year overall survival was 52.5% in the P-Gemox+Thal arm and 48.9% in the AspaMetDex arm (P=0.935).
Overall safety
Rates of leukopenia, thrombocytopenia, and ALT/AST increase were all significantly higher with P-Gemox+Thal than with AspaMetDex—100% vs 66.7% (P<0.001), 64.2% vs 35.2% (P=0.005), and 69.6% vs 64.8% (P=0.004), respectively.
Rates of anemia and edema were significantly higher with AspaMetDex than with P-Gemox+Thal—51.8% vs 77.8% (P=0.005) and 37.5% vs 66.7% (P=0.003), respectively.
There were 3 treatment-related deaths in the AspaMetDex arm but none in the P-Gemox+Thal arm. Two of the treatment-related deaths—from severe acute renal failure and sepsis—occurred in the first cycle, and 1 death—due to severe sepsis—occurred in the third cycle.
The median hospitalization time was significantly shorter in the P-Gemox+Thal arm than the AspaMetDex arm—1.9 days and 4.9 days, respectively (P<0.01).
Based on these results, Dr Huang said P-Gemox+Thal may be more tolerable and provide more convenient administration than AspaMetDex.
Photo by Larry Young
SAN FRANCISCO—Interim results of a phase 3 trial suggest 2 treatment regimens may provide comparable efficacy in patients with extranodal natural killer/T-cell lymphoma (ENKTL), though 1 regimen appears more toxic than the other.
In this ongoing trial, investigators are comparing pegaspargase, gemcitabine, oxaliplatin, and thalidomide (P-Gemox+Thal) to pegaspargase, methotrexate, calcium folinate, and dexamethasone (AspaMetDex).
In some patients, either regimen may be followed by extensive involved-field radiotherapy (EIFRT) or autologous hematopoietic stem cell transplant (ASCT).
Thus far, P-Gemox+Thal and AspaMetDex have proven similarly effective for patients with newly diagnosed, stage I/II ENKTL.
And both regimens have produced unsatisfying survival outcomes in patients with advanced or relapsed/refractory ENKTL, according to investigator Huiqiang Huang, MD, of Sun Yat-sen Institute of Hematology in Guangzhou, China.
In addition, P-Gemox+Thal seems to be less toxic, overall, than AspaMetDex.
However, Dr Huang said it is still too early to draw any firm conclusions about these regimens.
He presented results from this trial at the 9th Annual T-cell Lymphoma Forum. Results were previously presented at the 2016 ASH Annual Meeting (abstract 1819).
Dr Huang noted that AspaMetDex and SMILE (dexamethasone, methotrexate, ifosfamide, lL-asparaginase, and etoposide) are frequently administered to patients with ENKTL. And P-Gemox is recommended in the 2016 NCCN guidelines.
“But optimal regimens still have not been fully defined,” he said.
Therefore, he and his colleagues decided to compare AspaMetDex to P-Gemox+Thal in this non-inferiority trial, which has enrolled 110 patients from 12 centers in China.
Treatment
Fifty-six patients have been randomized to receive P-Gemox+Thal. Every 3 weeks, they received pegaspargase at 2000 U/m2 on day 1, gemcitabine at 1000 mg/m2 on days 1 and 8, and oxaliplatin at 130 mg/m2 on days 1 and 8. They also received thalidomide at 100 mg every day for 1 year.
Fifty-four patients have been randomized to receive AspaMetDex. Every 3 weeks, they received pegaspargase at 2000 U/m2 on day 1, methotrexate at 3000 mg/m2 on day 1, calcium folinate at 30 mg every 6 hours until a safe serum methotrexate concentration was reached, and dexamethasone at 40 mg every day on days 1 to 4.
Newly diagnosed patients with stage I/II disease received either regimen as induction for a maximum of 4 cycles. Responders went on to receive EIFRT at 56 Gy in 28 fractions over 4 weeks.
Patients with newly diagnosed, stage III/IV ENKTL or relapsed/refractory ENKTL received either chemotherapy regimen for a maximum of 6 cycles. If they achieved a complete response (CR), these patients could proceed to ASCT.
Stage I/II ENKTL
Of the 63 stage I/II patients, 33 were randomized to P-Gemox+Thal, and 30 received AspaMetDex. In both arms, most patients were male (69.7% and 70%, respectively) and younger than 60 (78.8% and 90%, respectively).
Ninety-seven percent of patients in the P-Gemox+Thal arm had an ECOG status of 0-1, as did 100% of patients in the AspaMetDex arm.
The overall response rate (ORR) was 85.2% in the P-Gemox+Thal arm and 81.5% in the AspaMetDex arm. The CR rate was 59.3% in both arms. The rate of stable disease was 3.7% in the P-Gemox+Thal arm and 11.1% in the AspaMetDex arm.
After EIFRT, the ORR increased to 92.6% in the P-Gemox+Thal arm, and the CR rate increased to 88.8%. In the AspaMetDex arm, the ORR increased to 88.8%, and the CR rate increased to 85.1%.
At a median follow-up of 13.5 months, the 2-year progression-free survival rate was 82.9% in the P-Gemox+Thal arm and 84.5% in the AspaMetDex arm (P=0.791).
The 2-year overall survival rates were 95.0% in the P-Gemox+Thal arm and 75.8% in the AspaMetDex arm (P=0.089).
Advanced, rel/ref ENKTL
Of the 47 patients with stage III/IV or relapsed/refractory ENKTL, 24 were randomized to P-Gemox+Thal, and 23 to AspaMetDex. In both arms, most patients were male (75% and 87%, respectively) and younger than 60 (95.8% and 91.3%, respectively).
ECOG status was 0 for 62.5% of patients in the P-Gemox+Thal arm and 73.9% of those in the AspaMetDex arm. ECOG status was 1 for 33.3% and 17.4%, respectively.
The ORR was 86.3% in the P-Gemox+Thal arm and 70% in the AspaMetDex arm. The CR rate was 50% in both arms.
The partial response rate was 36.3% in the P-Gemox+Thal arm and 20% in the AspaMetDex arm. And the rate of stable disease was 13.6% and 15%, respectively.
Three patients in each treatment arm went on to ASCT after CR. A total of 3 patients relapsed within 6 months of ASCT—2 in the P-Gemox+Thal arm and 1 in the AspaMetDex arm. Two patients died of disease progression.
At a median follow-up of 14.5 months, the 2-year progression-free survival was 12.2 months in the P-Gemox+Thal arm and 7.6 months in the AspaMetDex arm (P=0.365).
The 2-year overall survival was 52.5% in the P-Gemox+Thal arm and 48.9% in the AspaMetDex arm (P=0.935).
Overall safety
Rates of leukopenia, thrombocytopenia, and ALT/AST increase were all significantly higher with P-Gemox+Thal than with AspaMetDex—100% vs 66.7% (P<0.001), 64.2% vs 35.2% (P=0.005), and 69.6% vs 64.8% (P=0.004), respectively.
Rates of anemia and edema were significantly higher with AspaMetDex than with P-Gemox+Thal—51.8% vs 77.8% (P=0.005) and 37.5% vs 66.7% (P=0.003), respectively.
There were 3 treatment-related deaths in the AspaMetDex arm but none in the P-Gemox+Thal arm. Two of the treatment-related deaths—from severe acute renal failure and sepsis—occurred in the first cycle, and 1 death—due to severe sepsis—occurred in the third cycle.
The median hospitalization time was significantly shorter in the P-Gemox+Thal arm than the AspaMetDex arm—1.9 days and 4.9 days, respectively (P<0.01).
Based on these results, Dr Huang said P-Gemox+Thal may be more tolerable and provide more convenient administration than AspaMetDex.
Photo by Larry Young
SAN FRANCISCO—Interim results of a phase 3 trial suggest 2 treatment regimens may provide comparable efficacy in patients with extranodal natural killer/T-cell lymphoma (ENKTL), though 1 regimen appears more toxic than the other.
In this ongoing trial, investigators are comparing pegaspargase, gemcitabine, oxaliplatin, and thalidomide (P-Gemox+Thal) to pegaspargase, methotrexate, calcium folinate, and dexamethasone (AspaMetDex).
In some patients, either regimen may be followed by extensive involved-field radiotherapy (EIFRT) or autologous hematopoietic stem cell transplant (ASCT).
Thus far, P-Gemox+Thal and AspaMetDex have proven similarly effective for patients with newly diagnosed, stage I/II ENKTL.
And both regimens have produced unsatisfying survival outcomes in patients with advanced or relapsed/refractory ENKTL, according to investigator Huiqiang Huang, MD, of Sun Yat-sen Institute of Hematology in Guangzhou, China.
In addition, P-Gemox+Thal seems to be less toxic, overall, than AspaMetDex.
However, Dr Huang said it is still too early to draw any firm conclusions about these regimens.
He presented results from this trial at the 9th Annual T-cell Lymphoma Forum. Results were previously presented at the 2016 ASH Annual Meeting (abstract 1819).
Dr Huang noted that AspaMetDex and SMILE (dexamethasone, methotrexate, ifosfamide, lL-asparaginase, and etoposide) are frequently administered to patients with ENKTL. And P-Gemox is recommended in the 2016 NCCN guidelines.
“But optimal regimens still have not been fully defined,” he said.
Therefore, he and his colleagues decided to compare AspaMetDex to P-Gemox+Thal in this non-inferiority trial, which has enrolled 110 patients from 12 centers in China.
Treatment
Fifty-six patients have been randomized to receive P-Gemox+Thal. Every 3 weeks, they received pegaspargase at 2000 U/m2 on day 1, gemcitabine at 1000 mg/m2 on days 1 and 8, and oxaliplatin at 130 mg/m2 on days 1 and 8. They also received thalidomide at 100 mg every day for 1 year.
Fifty-four patients have been randomized to receive AspaMetDex. Every 3 weeks, they received pegaspargase at 2000 U/m2 on day 1, methotrexate at 3000 mg/m2 on day 1, calcium folinate at 30 mg every 6 hours until a safe serum methotrexate concentration was reached, and dexamethasone at 40 mg every day on days 1 to 4.
Newly diagnosed patients with stage I/II disease received either regimen as induction for a maximum of 4 cycles. Responders went on to receive EIFRT at 56 Gy in 28 fractions over 4 weeks.
Patients with newly diagnosed, stage III/IV ENKTL or relapsed/refractory ENKTL received either chemotherapy regimen for a maximum of 6 cycles. If they achieved a complete response (CR), these patients could proceed to ASCT.
Stage I/II ENKTL
Of the 63 stage I/II patients, 33 were randomized to P-Gemox+Thal, and 30 received AspaMetDex. In both arms, most patients were male (69.7% and 70%, respectively) and younger than 60 (78.8% and 90%, respectively).
Ninety-seven percent of patients in the P-Gemox+Thal arm had an ECOG status of 0-1, as did 100% of patients in the AspaMetDex arm.
The overall response rate (ORR) was 85.2% in the P-Gemox+Thal arm and 81.5% in the AspaMetDex arm. The CR rate was 59.3% in both arms. The rate of stable disease was 3.7% in the P-Gemox+Thal arm and 11.1% in the AspaMetDex arm.
After EIFRT, the ORR increased to 92.6% in the P-Gemox+Thal arm, and the CR rate increased to 88.8%. In the AspaMetDex arm, the ORR increased to 88.8%, and the CR rate increased to 85.1%.
At a median follow-up of 13.5 months, the 2-year progression-free survival rate was 82.9% in the P-Gemox+Thal arm and 84.5% in the AspaMetDex arm (P=0.791).
The 2-year overall survival rates were 95.0% in the P-Gemox+Thal arm and 75.8% in the AspaMetDex arm (P=0.089).
Advanced, rel/ref ENKTL
Of the 47 patients with stage III/IV or relapsed/refractory ENKTL, 24 were randomized to P-Gemox+Thal, and 23 to AspaMetDex. In both arms, most patients were male (75% and 87%, respectively) and younger than 60 (95.8% and 91.3%, respectively).
ECOG status was 0 for 62.5% of patients in the P-Gemox+Thal arm and 73.9% of those in the AspaMetDex arm. ECOG status was 1 for 33.3% and 17.4%, respectively.
The ORR was 86.3% in the P-Gemox+Thal arm and 70% in the AspaMetDex arm. The CR rate was 50% in both arms.
The partial response rate was 36.3% in the P-Gemox+Thal arm and 20% in the AspaMetDex arm. And the rate of stable disease was 13.6% and 15%, respectively.
Three patients in each treatment arm went on to ASCT after CR. A total of 3 patients relapsed within 6 months of ASCT—2 in the P-Gemox+Thal arm and 1 in the AspaMetDex arm. Two patients died of disease progression.
At a median follow-up of 14.5 months, the 2-year progression-free survival was 12.2 months in the P-Gemox+Thal arm and 7.6 months in the AspaMetDex arm (P=0.365).
The 2-year overall survival was 52.5% in the P-Gemox+Thal arm and 48.9% in the AspaMetDex arm (P=0.935).
Overall safety
Rates of leukopenia, thrombocytopenia, and ALT/AST increase were all significantly higher with P-Gemox+Thal than with AspaMetDex—100% vs 66.7% (P<0.001), 64.2% vs 35.2% (P=0.005), and 69.6% vs 64.8% (P=0.004), respectively.
Rates of anemia and edema were significantly higher with AspaMetDex than with P-Gemox+Thal—51.8% vs 77.8% (P=0.005) and 37.5% vs 66.7% (P=0.003), respectively.
There were 3 treatment-related deaths in the AspaMetDex arm but none in the P-Gemox+Thal arm. Two of the treatment-related deaths—from severe acute renal failure and sepsis—occurred in the first cycle, and 1 death—due to severe sepsis—occurred in the third cycle.
The median hospitalization time was significantly shorter in the P-Gemox+Thal arm than the AspaMetDex arm—1.9 days and 4.9 days, respectively (P<0.01).
Based on these results, Dr Huang said P-Gemox+Thal may be more tolerable and provide more convenient administration than AspaMetDex.
Group proposes new prognostic model for PTCL-NOS
T-cell Lymphoma Forum
Photo by Larry Young
SAN FRANCISCO—Researchers have used data from the T-Cell Project (TCP) to create a prognostic model for peripheral T-cell lymphoma not otherwise specified (PTCL-NOS).
Analyses have suggested the TCP model is more accurate for PTCL-NOS than 4 other prognostic models—the International Prognostic Index (IPI), the Prognostic Index for T-cell Lymphoma (PIT), the International Peripheral T-cell Lymphoma Project score (IPTCLP), and the modified PIT (mPIT).
Massimo Federico, MD, of the University of Modena and Reggio Emilia in Italy, described the TCP model at the 9th Annual T-cell Lymphoma Forum.
Creating the model
TCP is a prospective registry that includes data from T-cell lymphoma patients in 15 countries located in 5 different regions of the world. As of December 31, 2016, 1523 cases of T-cell lymphoma have been registered with TCP.
Dr Federico and his colleagues used these data to create their prognostic model. There were 311 patients with PTCL-NOS who had adequate data for analysis. The 5-year overall survival (OS) for these patients was 36%.
The researchers chose 13 variables from the literature that have been reported to have a prognostic impact on survival in PTCL-NOS:
- Age > 60
- Lactate dehydrogenase > upper limit of normal
- Albumin < 3.5 g/dL
- Hemoglobin < 12 g/dL
- Platelets < 150/mm3
- Lymphocyte to monocyte ratio ≤ 2.1
- Neutrophil to lymphocyte ratio > 6.5
- Absolute neutrophil count (ANC) > 6.5/mm3
- ECOG performance status > 1
- Stage III-IV disease
- B symptoms
- Extra nodal sites > 1
- Male gender.
In univariate analysis, nearly all of these factors were significantly associated with OS in the cohort of TCP patients. (The 2 exceptions were age older than 60 and having more than 1 extranodal site.)
However, Dr Federico and his colleagues said the factors with the greatest prognostic impact were:
- ECOG performance status > 1, with a hazard ratio (HR) of 2.12 (P<0.001)
- Albumin < 3.5 g/dL, with an HR of 2.03 (P<0.001)
- ANC > 6.5/mm3, with an HR of 1.85 (P<0.001)
- Stage III-IV disease, with an HR of 1.74 (P=0.010).
So the researchers used these factors in their model, which has 3 risk categories.
Risk categories
Patients were considered low-risk if they had 0 of the 4 risk factors. These patients had a 3-year OS of 76% and a 5-year OS of 69%.
Patients were considered intermediate-risk if they had 1 to 2 risk factors. These patients had a 3-year OS of 43% and a 5-year OS of 31%. Compared to low-risk patients, the HR was 3.08 (P<0.001).
Patients were considered high-risk if they had 3 to 4 risk factors. The 3-year OS was 11% for these patients, and the 5-year OS was 8%.
The HR was 8.88 (P<0.001) for high-risk compared to low-risk patients and 2.88 (P<0.001) for high-risk compared to intermediate-risk patients.
Validation
The researchers tested the TCP model in a validation cohort of 98 patients from the COMPLETE registry. As with the training cohort of TCP patients, the model revealed 3 different risk groups (in terms of OS) in the validation cohort.
Dr Federico noted that there were no significant differences between the training and validation cohorts, except when it came to follow-up. The median follow-up was 46 months in the TCP group and 18 months in the COMPLETE group.
The researchers also found the TCP could classify patients into 3 different risk groups according to progression-free survival.
Comparison
Finally, Dr Federico and his colleagues compared the TCP model to the IPI, PIT, IPTCLP, and mPIT models using 208 patients.
“The discriminant power of the proposed model is superior to the others in terms of all of the statistical tests we adopted,” Dr Federico said.
| Model | c-Harrell*
(95% CI) |
D-Royston
(SE) |
R2 | AIC (95% CI) | AUC,
3-year OS |
| TCP | 0.666 (0.618-0.713) | 1.152 (0.191) | 0.31 (0.14-0.46) | 983 | 0.714 |
| PIT | 0.614 (0.563-0.664) | 0.750 (0.195) | 0.15 (0.06-0.31) | 1004 | 0.696 |
| IPI | 0.645 (0.594-0.696) | 0.883 (0.191) | 0.22 (0.08-0.38) | 987 | 0.704 |
| IPITCLP | 0.606 (0.549-0.663) | 0.631 (0.188) | 0.12 (0.03-0.28) | 1006 | 0.704 |
| mPIT | 0.640 (0.586-0.694) | 0.762 (0.170) | 0.16 (0.05-0.33) | 999 | 0.681 |
In closing, Dr Federico said the TCP model clearly defines risk groups in PTCL-NOS and identifies patients with relatively good prognosis.
However, there is a need for emerging biologic variables to be tested for prognostic value and included in prognostic tools to allow for better risk stratification.
*c-Harrel: Harrell’s concordance index, 95% CI: confidence interval, D-Royston: Royston/Sauerbrei’s D statistic (Stat Med 2004 Mar 15, 23[5]:723-48), SE: standard error, R2: explained randomness, AIC: Akaike information criterion, AUC: area under the curve (according to Heagerty et al, Biometrics, 2000 Jun, 56[2]:337-44).
T-cell Lymphoma Forum
Photo by Larry Young
SAN FRANCISCO—Researchers have used data from the T-Cell Project (TCP) to create a prognostic model for peripheral T-cell lymphoma not otherwise specified (PTCL-NOS).
Analyses have suggested the TCP model is more accurate for PTCL-NOS than 4 other prognostic models—the International Prognostic Index (IPI), the Prognostic Index for T-cell Lymphoma (PIT), the International Peripheral T-cell Lymphoma Project score (IPTCLP), and the modified PIT (mPIT).
Massimo Federico, MD, of the University of Modena and Reggio Emilia in Italy, described the TCP model at the 9th Annual T-cell Lymphoma Forum.
Creating the model
TCP is a prospective registry that includes data from T-cell lymphoma patients in 15 countries located in 5 different regions of the world. As of December 31, 2016, 1523 cases of T-cell lymphoma have been registered with TCP.
Dr Federico and his colleagues used these data to create their prognostic model. There were 311 patients with PTCL-NOS who had adequate data for analysis. The 5-year overall survival (OS) for these patients was 36%.
The researchers chose 13 variables from the literature that have been reported to have a prognostic impact on survival in PTCL-NOS:
- Age > 60
- Lactate dehydrogenase > upper limit of normal
- Albumin < 3.5 g/dL
- Hemoglobin < 12 g/dL
- Platelets < 150/mm3
- Lymphocyte to monocyte ratio ≤ 2.1
- Neutrophil to lymphocyte ratio > 6.5
- Absolute neutrophil count (ANC) > 6.5/mm3
- ECOG performance status > 1
- Stage III-IV disease
- B symptoms
- Extra nodal sites > 1
- Male gender.
In univariate analysis, nearly all of these factors were significantly associated with OS in the cohort of TCP patients. (The 2 exceptions were age older than 60 and having more than 1 extranodal site.)
However, Dr Federico and his colleagues said the factors with the greatest prognostic impact were:
- ECOG performance status > 1, with a hazard ratio (HR) of 2.12 (P<0.001)
- Albumin < 3.5 g/dL, with an HR of 2.03 (P<0.001)
- ANC > 6.5/mm3, with an HR of 1.85 (P<0.001)
- Stage III-IV disease, with an HR of 1.74 (P=0.010).
So the researchers used these factors in their model, which has 3 risk categories.
Risk categories
Patients were considered low-risk if they had 0 of the 4 risk factors. These patients had a 3-year OS of 76% and a 5-year OS of 69%.
Patients were considered intermediate-risk if they had 1 to 2 risk factors. These patients had a 3-year OS of 43% and a 5-year OS of 31%. Compared to low-risk patients, the HR was 3.08 (P<0.001).
Patients were considered high-risk if they had 3 to 4 risk factors. The 3-year OS was 11% for these patients, and the 5-year OS was 8%.
The HR was 8.88 (P<0.001) for high-risk compared to low-risk patients and 2.88 (P<0.001) for high-risk compared to intermediate-risk patients.
Validation
The researchers tested the TCP model in a validation cohort of 98 patients from the COMPLETE registry. As with the training cohort of TCP patients, the model revealed 3 different risk groups (in terms of OS) in the validation cohort.
Dr Federico noted that there were no significant differences between the training and validation cohorts, except when it came to follow-up. The median follow-up was 46 months in the TCP group and 18 months in the COMPLETE group.
The researchers also found the TCP could classify patients into 3 different risk groups according to progression-free survival.
Comparison
Finally, Dr Federico and his colleagues compared the TCP model to the IPI, PIT, IPTCLP, and mPIT models using 208 patients.
“The discriminant power of the proposed model is superior to the others in terms of all of the statistical tests we adopted,” Dr Federico said.
| Model | c-Harrell*
(95% CI) |
D-Royston
(SE) |
R2 | AIC (95% CI) | AUC,
3-year OS |
| TCP | 0.666 (0.618-0.713) | 1.152 (0.191) | 0.31 (0.14-0.46) | 983 | 0.714 |
| PIT | 0.614 (0.563-0.664) | 0.750 (0.195) | 0.15 (0.06-0.31) | 1004 | 0.696 |
| IPI | 0.645 (0.594-0.696) | 0.883 (0.191) | 0.22 (0.08-0.38) | 987 | 0.704 |
| IPITCLP | 0.606 (0.549-0.663) | 0.631 (0.188) | 0.12 (0.03-0.28) | 1006 | 0.704 |
| mPIT | 0.640 (0.586-0.694) | 0.762 (0.170) | 0.16 (0.05-0.33) | 999 | 0.681 |
In closing, Dr Federico said the TCP model clearly defines risk groups in PTCL-NOS and identifies patients with relatively good prognosis.
However, there is a need for emerging biologic variables to be tested for prognostic value and included in prognostic tools to allow for better risk stratification.
*c-Harrel: Harrell’s concordance index, 95% CI: confidence interval, D-Royston: Royston/Sauerbrei’s D statistic (Stat Med 2004 Mar 15, 23[5]:723-48), SE: standard error, R2: explained randomness, AIC: Akaike information criterion, AUC: area under the curve (according to Heagerty et al, Biometrics, 2000 Jun, 56[2]:337-44).
T-cell Lymphoma Forum
Photo by Larry Young
SAN FRANCISCO—Researchers have used data from the T-Cell Project (TCP) to create a prognostic model for peripheral T-cell lymphoma not otherwise specified (PTCL-NOS).
Analyses have suggested the TCP model is more accurate for PTCL-NOS than 4 other prognostic models—the International Prognostic Index (IPI), the Prognostic Index for T-cell Lymphoma (PIT), the International Peripheral T-cell Lymphoma Project score (IPTCLP), and the modified PIT (mPIT).
Massimo Federico, MD, of the University of Modena and Reggio Emilia in Italy, described the TCP model at the 9th Annual T-cell Lymphoma Forum.
Creating the model
TCP is a prospective registry that includes data from T-cell lymphoma patients in 15 countries located in 5 different regions of the world. As of December 31, 2016, 1523 cases of T-cell lymphoma have been registered with TCP.
Dr Federico and his colleagues used these data to create their prognostic model. There were 311 patients with PTCL-NOS who had adequate data for analysis. The 5-year overall survival (OS) for these patients was 36%.
The researchers chose 13 variables from the literature that have been reported to have a prognostic impact on survival in PTCL-NOS:
- Age > 60
- Lactate dehydrogenase > upper limit of normal
- Albumin < 3.5 g/dL
- Hemoglobin < 12 g/dL
- Platelets < 150/mm3
- Lymphocyte to monocyte ratio ≤ 2.1
- Neutrophil to lymphocyte ratio > 6.5
- Absolute neutrophil count (ANC) > 6.5/mm3
- ECOG performance status > 1
- Stage III-IV disease
- B symptoms
- Extra nodal sites > 1
- Male gender.
In univariate analysis, nearly all of these factors were significantly associated with OS in the cohort of TCP patients. (The 2 exceptions were age older than 60 and having more than 1 extranodal site.)
However, Dr Federico and his colleagues said the factors with the greatest prognostic impact were:
- ECOG performance status > 1, with a hazard ratio (HR) of 2.12 (P<0.001)
- Albumin < 3.5 g/dL, with an HR of 2.03 (P<0.001)
- ANC > 6.5/mm3, with an HR of 1.85 (P<0.001)
- Stage III-IV disease, with an HR of 1.74 (P=0.010).
So the researchers used these factors in their model, which has 3 risk categories.
Risk categories
Patients were considered low-risk if they had 0 of the 4 risk factors. These patients had a 3-year OS of 76% and a 5-year OS of 69%.
Patients were considered intermediate-risk if they had 1 to 2 risk factors. These patients had a 3-year OS of 43% and a 5-year OS of 31%. Compared to low-risk patients, the HR was 3.08 (P<0.001).
Patients were considered high-risk if they had 3 to 4 risk factors. The 3-year OS was 11% for these patients, and the 5-year OS was 8%.
The HR was 8.88 (P<0.001) for high-risk compared to low-risk patients and 2.88 (P<0.001) for high-risk compared to intermediate-risk patients.
Validation
The researchers tested the TCP model in a validation cohort of 98 patients from the COMPLETE registry. As with the training cohort of TCP patients, the model revealed 3 different risk groups (in terms of OS) in the validation cohort.
Dr Federico noted that there were no significant differences between the training and validation cohorts, except when it came to follow-up. The median follow-up was 46 months in the TCP group and 18 months in the COMPLETE group.
The researchers also found the TCP could classify patients into 3 different risk groups according to progression-free survival.
Comparison
Finally, Dr Federico and his colleagues compared the TCP model to the IPI, PIT, IPTCLP, and mPIT models using 208 patients.
“The discriminant power of the proposed model is superior to the others in terms of all of the statistical tests we adopted,” Dr Federico said.
| Model | c-Harrell*
(95% CI) |
D-Royston
(SE) |
R2 | AIC (95% CI) | AUC,
3-year OS |
| TCP | 0.666 (0.618-0.713) | 1.152 (0.191) | 0.31 (0.14-0.46) | 983 | 0.714 |
| PIT | 0.614 (0.563-0.664) | 0.750 (0.195) | 0.15 (0.06-0.31) | 1004 | 0.696 |
| IPI | 0.645 (0.594-0.696) | 0.883 (0.191) | 0.22 (0.08-0.38) | 987 | 0.704 |
| IPITCLP | 0.606 (0.549-0.663) | 0.631 (0.188) | 0.12 (0.03-0.28) | 1006 | 0.704 |
| mPIT | 0.640 (0.586-0.694) | 0.762 (0.170) | 0.16 (0.05-0.33) | 999 | 0.681 |
In closing, Dr Federico said the TCP model clearly defines risk groups in PTCL-NOS and identifies patients with relatively good prognosis.
However, there is a need for emerging biologic variables to be tested for prognostic value and included in prognostic tools to allow for better risk stratification.
*c-Harrel: Harrell’s concordance index, 95% CI: confidence interval, D-Royston: Royston/Sauerbrei’s D statistic (Stat Med 2004 Mar 15, 23[5]:723-48), SE: standard error, R2: explained randomness, AIC: Akaike information criterion, AUC: area under the curve (according to Heagerty et al, Biometrics, 2000 Jun, 56[2]:337-44).
Project provides insight into T-cell lymphoma
Photo by Larry Young
SAN FRANCISCO—The T-Cell Project has provided information that can enhance our understanding of T-cell lymphomas, according to a presentation at the 9th Annual T-cell Lymphoma Forum.
The project is a prospective registry that includes data from T-cell lymphoma patients in 15 countries located in 5 different regions of the world.
The data showed that peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the most common subtype of T-cell lymphoma in all 5 regions, although the distribution of other subtypes varies.
A majority of patients in the registry received chemotherapy as induction, and anthracycline-containing regimens were the most popular treatment choice.
Although 60% of patients in the registry had low-risk or low/intermediate-risk disease, progression-free survival (PFS) and overall survival (OS) rates were low. The 5-year PFS was 32%, and the 5-year OS was 42%.
Massimo Federico, MD, of the University of Modena and Reggio Emilia in Italy, presented these data at the meeting.
About the project
Dr Federico said the goals of the T-Cell Project are to determine if prospective data collection provides more accurate information to better define prognosis of the most frequent subtypes of T-cell lymphoma and to improve our knowledge of clinical and biological characteristics, as well as outcomes, of the more uncommon subtypes.
“Why did we choose to propose a prospective registry for the collection of information in T-cell lymphoma?” Dr Federico asked. “Because it is, by far, less expensive than a clinical trial, but also because it can offer excellent data for generating new research programs and is a great opportunity for academic cooperation.”
As of December 31, 2016, the registry included 1523 patients. There were 75 sites (with at least 1 patient) active in the registry.
Fifteen countries in 5 geographic regions were represented. Europe was the greatest contributor (44%), followed by North America (US only, 25%), South America (20%), the Far East (9%), the Middle East (2%), and Oceania (<1%).
Subtypes
Overall, the distribution of the different T-cell lymphoma subtypes is as follows:
PTCL-NOS—36%
Angioimmunoblastic T-cell lymphoma (AITL)—17%
ALK- anaplastic large-cell lymphoma (ALCL)—16%
NK/T-cell lymphoma (NKTCL)—11%
ALK+ ALCL—8%
Enteropathy-associated T-cell lymphoma—4%
Unclassifiable T-cell lymphoma—3%
Hepatosplenic T-cell lymphoma—2%
Subcutaneous panniculitis-like T-cell lymphoma—2%
Peripheral gamma delta T-cell lymphoma—1%
Geographic distribution
The most common T-cell lymphoma subtypes in Europe were PTCL-NOS (37%), AITL (21%), and ALK- ALCL (14%). Likewise, the most common subtypes in the US were PTCL-NOS (35%), AITL (21%), and ALK- ALCL (13%).
In the Middle East, the most common subtypes were PTCL-NOS (40%), AITL (16%), and ALK+ ALCL (13%). In South America, they were PTCL-NOS (41%), ALK- ALCL (26%), and NKTCL (10%). And in Asia, they were PTCL-NOS (29%), NKTCL (29%), and AITL (17%).
Patient characteristics
Dr Federico presented data on patient characteristics for 1391 individuals, validated as of April 30, 2016.
The patients’ median age was 56 (range, 18-89). Forty-four percent were 60 or older, and 60% were male. Twenty-six percent had ECOG performance status > 1, 50% had B symptoms, and 72% had disease-related discomfort.
Sixty percent had low-risk or low/intermediate-risk disease according to the International Prognostic Index (IPI) and the Prognostic Index for T-cell Lymphoma (PIT).
Treatment
Treatment details are available for 1022 patients. Ninety-two percent received therapy with curative intent.
For induction, 76% of patients received chemotherapy alone, 14% received chemotherapy and radiotherapy, 8% received best supportive care, and 2% received radiotherapy alone.
Seventy-one percent of patients who received chemotherapy had an anthracycline-containing regimen, 13% received etoposide-containing chemotherapy, 9% received chemotherapy containing an anthracycline and etoposide, and 7% of patients received other therapy.
Thirteen percent of patients received a transplant as salvage treatment, and 7% received a transplant as consolidation.
Outcomes
Data on patient responses to initial treatment were available for 888 individuals. The 84 patients who received best supportive care were not included, and 50 patients were not evaluable for response.
The complete response/unconfirmed complete response rate was 53%, and the partial response rate was 19%. Twenty-eight percent of patients had no response or progressed.
The median PFS was 16 months. The 5-year PFS rate was 32% overall, 23% for PTCL-NOS, 28% for AITL, 39% for ALK- ALCL, and 57% for ALK+ ALCL.
The median OS was 36 months. The 5-year OS was 42% overall, 34% for PTCL-NOS, 42% for AITL, 46% for ALK- ALCL, and 76% for ALK+ ALCL.
Dr Federico and his colleagues have used these data to develop a prognostic model for PTCL-NOS that, they say, is more accurate than current models.
Photo by Larry Young
SAN FRANCISCO—The T-Cell Project has provided information that can enhance our understanding of T-cell lymphomas, according to a presentation at the 9th Annual T-cell Lymphoma Forum.
The project is a prospective registry that includes data from T-cell lymphoma patients in 15 countries located in 5 different regions of the world.
The data showed that peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the most common subtype of T-cell lymphoma in all 5 regions, although the distribution of other subtypes varies.
A majority of patients in the registry received chemotherapy as induction, and anthracycline-containing regimens were the most popular treatment choice.
Although 60% of patients in the registry had low-risk or low/intermediate-risk disease, progression-free survival (PFS) and overall survival (OS) rates were low. The 5-year PFS was 32%, and the 5-year OS was 42%.
Massimo Federico, MD, of the University of Modena and Reggio Emilia in Italy, presented these data at the meeting.
About the project
Dr Federico said the goals of the T-Cell Project are to determine if prospective data collection provides more accurate information to better define prognosis of the most frequent subtypes of T-cell lymphoma and to improve our knowledge of clinical and biological characteristics, as well as outcomes, of the more uncommon subtypes.
“Why did we choose to propose a prospective registry for the collection of information in T-cell lymphoma?” Dr Federico asked. “Because it is, by far, less expensive than a clinical trial, but also because it can offer excellent data for generating new research programs and is a great opportunity for academic cooperation.”
As of December 31, 2016, the registry included 1523 patients. There were 75 sites (with at least 1 patient) active in the registry.
Fifteen countries in 5 geographic regions were represented. Europe was the greatest contributor (44%), followed by North America (US only, 25%), South America (20%), the Far East (9%), the Middle East (2%), and Oceania (<1%).
Subtypes
Overall, the distribution of the different T-cell lymphoma subtypes is as follows:
PTCL-NOS—36%
Angioimmunoblastic T-cell lymphoma (AITL)—17%
ALK- anaplastic large-cell lymphoma (ALCL)—16%
NK/T-cell lymphoma (NKTCL)—11%
ALK+ ALCL—8%
Enteropathy-associated T-cell lymphoma—4%
Unclassifiable T-cell lymphoma—3%
Hepatosplenic T-cell lymphoma—2%
Subcutaneous panniculitis-like T-cell lymphoma—2%
Peripheral gamma delta T-cell lymphoma—1%
Geographic distribution
The most common T-cell lymphoma subtypes in Europe were PTCL-NOS (37%), AITL (21%), and ALK- ALCL (14%). Likewise, the most common subtypes in the US were PTCL-NOS (35%), AITL (21%), and ALK- ALCL (13%).
In the Middle East, the most common subtypes were PTCL-NOS (40%), AITL (16%), and ALK+ ALCL (13%). In South America, they were PTCL-NOS (41%), ALK- ALCL (26%), and NKTCL (10%). And in Asia, they were PTCL-NOS (29%), NKTCL (29%), and AITL (17%).
Patient characteristics
Dr Federico presented data on patient characteristics for 1391 individuals, validated as of April 30, 2016.
The patients’ median age was 56 (range, 18-89). Forty-four percent were 60 or older, and 60% were male. Twenty-six percent had ECOG performance status > 1, 50% had B symptoms, and 72% had disease-related discomfort.
Sixty percent had low-risk or low/intermediate-risk disease according to the International Prognostic Index (IPI) and the Prognostic Index for T-cell Lymphoma (PIT).
Treatment
Treatment details are available for 1022 patients. Ninety-two percent received therapy with curative intent.
For induction, 76% of patients received chemotherapy alone, 14% received chemotherapy and radiotherapy, 8% received best supportive care, and 2% received radiotherapy alone.
Seventy-one percent of patients who received chemotherapy had an anthracycline-containing regimen, 13% received etoposide-containing chemotherapy, 9% received chemotherapy containing an anthracycline and etoposide, and 7% of patients received other therapy.
Thirteen percent of patients received a transplant as salvage treatment, and 7% received a transplant as consolidation.
Outcomes
Data on patient responses to initial treatment were available for 888 individuals. The 84 patients who received best supportive care were not included, and 50 patients were not evaluable for response.
The complete response/unconfirmed complete response rate was 53%, and the partial response rate was 19%. Twenty-eight percent of patients had no response or progressed.
The median PFS was 16 months. The 5-year PFS rate was 32% overall, 23% for PTCL-NOS, 28% for AITL, 39% for ALK- ALCL, and 57% for ALK+ ALCL.
The median OS was 36 months. The 5-year OS was 42% overall, 34% for PTCL-NOS, 42% for AITL, 46% for ALK- ALCL, and 76% for ALK+ ALCL.
Dr Federico and his colleagues have used these data to develop a prognostic model for PTCL-NOS that, they say, is more accurate than current models.
Photo by Larry Young
SAN FRANCISCO—The T-Cell Project has provided information that can enhance our understanding of T-cell lymphomas, according to a presentation at the 9th Annual T-cell Lymphoma Forum.
The project is a prospective registry that includes data from T-cell lymphoma patients in 15 countries located in 5 different regions of the world.
The data showed that peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the most common subtype of T-cell lymphoma in all 5 regions, although the distribution of other subtypes varies.
A majority of patients in the registry received chemotherapy as induction, and anthracycline-containing regimens were the most popular treatment choice.
Although 60% of patients in the registry had low-risk or low/intermediate-risk disease, progression-free survival (PFS) and overall survival (OS) rates were low. The 5-year PFS was 32%, and the 5-year OS was 42%.
Massimo Federico, MD, of the University of Modena and Reggio Emilia in Italy, presented these data at the meeting.
About the project
Dr Federico said the goals of the T-Cell Project are to determine if prospective data collection provides more accurate information to better define prognosis of the most frequent subtypes of T-cell lymphoma and to improve our knowledge of clinical and biological characteristics, as well as outcomes, of the more uncommon subtypes.
“Why did we choose to propose a prospective registry for the collection of information in T-cell lymphoma?” Dr Federico asked. “Because it is, by far, less expensive than a clinical trial, but also because it can offer excellent data for generating new research programs and is a great opportunity for academic cooperation.”
As of December 31, 2016, the registry included 1523 patients. There were 75 sites (with at least 1 patient) active in the registry.
Fifteen countries in 5 geographic regions were represented. Europe was the greatest contributor (44%), followed by North America (US only, 25%), South America (20%), the Far East (9%), the Middle East (2%), and Oceania (<1%).
Subtypes
Overall, the distribution of the different T-cell lymphoma subtypes is as follows:
PTCL-NOS—36%
Angioimmunoblastic T-cell lymphoma (AITL)—17%
ALK- anaplastic large-cell lymphoma (ALCL)—16%
NK/T-cell lymphoma (NKTCL)—11%
ALK+ ALCL—8%
Enteropathy-associated T-cell lymphoma—4%
Unclassifiable T-cell lymphoma—3%
Hepatosplenic T-cell lymphoma—2%
Subcutaneous panniculitis-like T-cell lymphoma—2%
Peripheral gamma delta T-cell lymphoma—1%
Geographic distribution
The most common T-cell lymphoma subtypes in Europe were PTCL-NOS (37%), AITL (21%), and ALK- ALCL (14%). Likewise, the most common subtypes in the US were PTCL-NOS (35%), AITL (21%), and ALK- ALCL (13%).
In the Middle East, the most common subtypes were PTCL-NOS (40%), AITL (16%), and ALK+ ALCL (13%). In South America, they were PTCL-NOS (41%), ALK- ALCL (26%), and NKTCL (10%). And in Asia, they were PTCL-NOS (29%), NKTCL (29%), and AITL (17%).
Patient characteristics
Dr Federico presented data on patient characteristics for 1391 individuals, validated as of April 30, 2016.
The patients’ median age was 56 (range, 18-89). Forty-four percent were 60 or older, and 60% were male. Twenty-six percent had ECOG performance status > 1, 50% had B symptoms, and 72% had disease-related discomfort.
Sixty percent had low-risk or low/intermediate-risk disease according to the International Prognostic Index (IPI) and the Prognostic Index for T-cell Lymphoma (PIT).
Treatment
Treatment details are available for 1022 patients. Ninety-two percent received therapy with curative intent.
For induction, 76% of patients received chemotherapy alone, 14% received chemotherapy and radiotherapy, 8% received best supportive care, and 2% received radiotherapy alone.
Seventy-one percent of patients who received chemotherapy had an anthracycline-containing regimen, 13% received etoposide-containing chemotherapy, 9% received chemotherapy containing an anthracycline and etoposide, and 7% of patients received other therapy.
Thirteen percent of patients received a transplant as salvage treatment, and 7% received a transplant as consolidation.
Outcomes
Data on patient responses to initial treatment were available for 888 individuals. The 84 patients who received best supportive care were not included, and 50 patients were not evaluable for response.
The complete response/unconfirmed complete response rate was 53%, and the partial response rate was 19%. Twenty-eight percent of patients had no response or progressed.
The median PFS was 16 months. The 5-year PFS rate was 32% overall, 23% for PTCL-NOS, 28% for AITL, 39% for ALK- ALCL, and 57% for ALK+ ALCL.
The median OS was 36 months. The 5-year OS was 42% overall, 34% for PTCL-NOS, 42% for AITL, 46% for ALK- ALCL, and 76% for ALK+ ALCL.
Dr Federico and his colleagues have used these data to develop a prognostic model for PTCL-NOS that, they say, is more accurate than current models.
Brentuximab vedotin bests standard of care in CTCL
Photo by Larry Young
SAN FRANCISCO—The phase 3 ALCANZA trial is the first to convincingly demonstrate that a new systemic agent can be more effective than standard of care (SOC) options for cutaneous T-cell lymphoma (CTCL), according to a speaker at the 9th Annual T-cell Lymphoma Forum.
The trial showed significant improvements in response, symptom burden, and progression-free survival (PFS) in patients with CD30-expressing CTCL who received brentuximab vedotin (BV), as compared to patients who received either bexarotene or methotrexate.
“[These are] compelling results that potentially may have practice-changing implications for the use of brentuximab in managing CD30-expressing CTCL patients who require systemic therapy,” said Youn H. Kim, MD, of Stanford University School of Medicine in California.
Dr Kim presented these results at this year’s T-cell Lymphoma Forum. The data were also presented at the recent ASH Annual Meeting (abstract 182).
The ALCANZA trial was sponsored by Millennium Pharmaceuticals, Inc. (now a part of Takeda Pharmaceutical Company Limited) and Seattle Genetics, Inc.
The study was designed to compare BV to the SOC options of methotrexate or bexarotene in patients with CD30-positive CTCL, including mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL).
There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg IV every 3 weeks for up to 48 weeks.
The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive methotrexate at 5 mg to 50 mg PO weekly or bexarotene at a target dose of 300 mg/m² PO daily for up to 48 weeks.
Patients received BV for a median of 36 weeks (12 cycles), bexarotene for a median of 17 weeks, and methotrexate for a median of 9 weeks. Three patients in the BV arm were still on treatment at the time of analysis.
Patient characteristics
The median age was 62 (range, 22-83) in the BV am and 59 (range, 22-83) in the SOC arm. More than half of patients in each arm were male—52% and 58%, respectively. And most patients in both arms had an ECOG performance status of 0-1—95% and 97%, respectively.
The median number of prior therapies was 4 (range, 0-13) in the BV arm and 3.5 (range, 1-15) in the SOC arm. The median number of systemic therapies was 2 in the BV arm (range, 0-11) and the SOC arm (range, 1-8).
“It was pretty well balanced in terms of baseline characteristics between the 2 arms,” Dr Kim said. “The brentuximab arm had more stage IV patients—in fact, 7 stage IVB in brentuximab and none in the standard of care. And more patients with ALCL [treated with BV] had extracutaneous disease.”
Among pcALCL patients, 44% in the BV arm had extracutaneous disease, compared to 27% in the SOC arm. Among MF patients, 67% in the BV arm had stage IIB-IVB disease, compared to 61% in the SOC arm.
Response
The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4).
“[ORR4] was felt to be more meaningful than ORR because it includes not only the response rate but also a duration element in a single endpoint,” Dr Kim said.
ORR4 was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).
For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.
Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).
For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.
Symptoms
“In CTCL, there’s significant quality of life issues that are not captured adequately by objective response measures, and this patient outcome is very important,” Dr Kim said. “[Quality of life in this study] was captured by Skindex-29, which is an established quality of life measure in skin diseases.”
Patients in the BV arm had a significantly higher reduction in symptom burden according to Skindex-29 than patients receiving SOC. The mean maximum reduction in Skindex-29 symptom domain was -27.96 points in the BV arm and -8.62 points in the SOC arm (P<0.0001).
PFS
PFS was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).
For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.
Safety
The overall rate of adverse events (AEs) was 95% in the BV arm and 90% in the SOC arm. The rate of grade 3 or higher AEs was 41% and 47%, respectively. And the rate of serious AEs was 29% in both arms.
AEs resulting in discontinuation occurred in 24% of patients in the BV arm and 8% in the SOC arm. In the BV arm, this included peripheral neuropathy (n=9), skin-related hypersensitivity (n=3), E coli infection (n=1), impetigo (n=1), pulmonary embolism (n=1), urticaria (n=1), and vertigo (n=1).
In the SOC arm, AEs leading to discontinuation included maculo-papular rash (n=1), asthenia (n=1), hematuria (n=1), hypernatremia (n=1), neutropenia (n=1), periorbital infection (n=1), and somnolence (n=1). One patient in each arm experienced more than 1 AE resulting in discontinuation.
The most common AEs of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).
The majority of the peripheral neuropathy events in the BV arm were grade 1 or 2—26% and 32%, respectively. The rate of grade 3 peripheral neuropathy events was 9%, and there were no grade 4 events.
Eighty-two percent of patients reported resolution or improvement in peripheral neuropathy events in the BV arm at a median of 22.9 months of follow-up.
There were no on-study deaths (occurring within 30 days of the last dose) in the SOC arm, but there were 4 in the BV arm. Three of the BV deaths were considered unrelated to the drug.
The 1 BV-related death was a result of multiple organ dysfunction syndrome attributed to tumor necrosis at visceral disease sites in a patient with T3bN0M1 pcALCL. The other 3 deaths were due to lymphoma progression, pulmonary embolism, and sepsis.
Photo by Larry Young
SAN FRANCISCO—The phase 3 ALCANZA trial is the first to convincingly demonstrate that a new systemic agent can be more effective than standard of care (SOC) options for cutaneous T-cell lymphoma (CTCL), according to a speaker at the 9th Annual T-cell Lymphoma Forum.
The trial showed significant improvements in response, symptom burden, and progression-free survival (PFS) in patients with CD30-expressing CTCL who received brentuximab vedotin (BV), as compared to patients who received either bexarotene or methotrexate.
“[These are] compelling results that potentially may have practice-changing implications for the use of brentuximab in managing CD30-expressing CTCL patients who require systemic therapy,” said Youn H. Kim, MD, of Stanford University School of Medicine in California.
Dr Kim presented these results at this year’s T-cell Lymphoma Forum. The data were also presented at the recent ASH Annual Meeting (abstract 182).
The ALCANZA trial was sponsored by Millennium Pharmaceuticals, Inc. (now a part of Takeda Pharmaceutical Company Limited) and Seattle Genetics, Inc.
The study was designed to compare BV to the SOC options of methotrexate or bexarotene in patients with CD30-positive CTCL, including mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL).
There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg IV every 3 weeks for up to 48 weeks.
The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive methotrexate at 5 mg to 50 mg PO weekly or bexarotene at a target dose of 300 mg/m² PO daily for up to 48 weeks.
Patients received BV for a median of 36 weeks (12 cycles), bexarotene for a median of 17 weeks, and methotrexate for a median of 9 weeks. Three patients in the BV arm were still on treatment at the time of analysis.
Patient characteristics
The median age was 62 (range, 22-83) in the BV am and 59 (range, 22-83) in the SOC arm. More than half of patients in each arm were male—52% and 58%, respectively. And most patients in both arms had an ECOG performance status of 0-1—95% and 97%, respectively.
The median number of prior therapies was 4 (range, 0-13) in the BV arm and 3.5 (range, 1-15) in the SOC arm. The median number of systemic therapies was 2 in the BV arm (range, 0-11) and the SOC arm (range, 1-8).
“It was pretty well balanced in terms of baseline characteristics between the 2 arms,” Dr Kim said. “The brentuximab arm had more stage IV patients—in fact, 7 stage IVB in brentuximab and none in the standard of care. And more patients with ALCL [treated with BV] had extracutaneous disease.”
Among pcALCL patients, 44% in the BV arm had extracutaneous disease, compared to 27% in the SOC arm. Among MF patients, 67% in the BV arm had stage IIB-IVB disease, compared to 61% in the SOC arm.
Response
The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4).
“[ORR4] was felt to be more meaningful than ORR because it includes not only the response rate but also a duration element in a single endpoint,” Dr Kim said.
ORR4 was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).
For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.
Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).
For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.
Symptoms
“In CTCL, there’s significant quality of life issues that are not captured adequately by objective response measures, and this patient outcome is very important,” Dr Kim said. “[Quality of life in this study] was captured by Skindex-29, which is an established quality of life measure in skin diseases.”
Patients in the BV arm had a significantly higher reduction in symptom burden according to Skindex-29 than patients receiving SOC. The mean maximum reduction in Skindex-29 symptom domain was -27.96 points in the BV arm and -8.62 points in the SOC arm (P<0.0001).
PFS
PFS was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).
For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.
Safety
The overall rate of adverse events (AEs) was 95% in the BV arm and 90% in the SOC arm. The rate of grade 3 or higher AEs was 41% and 47%, respectively. And the rate of serious AEs was 29% in both arms.
AEs resulting in discontinuation occurred in 24% of patients in the BV arm and 8% in the SOC arm. In the BV arm, this included peripheral neuropathy (n=9), skin-related hypersensitivity (n=3), E coli infection (n=1), impetigo (n=1), pulmonary embolism (n=1), urticaria (n=1), and vertigo (n=1).
In the SOC arm, AEs leading to discontinuation included maculo-papular rash (n=1), asthenia (n=1), hematuria (n=1), hypernatremia (n=1), neutropenia (n=1), periorbital infection (n=1), and somnolence (n=1). One patient in each arm experienced more than 1 AE resulting in discontinuation.
The most common AEs of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).
The majority of the peripheral neuropathy events in the BV arm were grade 1 or 2—26% and 32%, respectively. The rate of grade 3 peripheral neuropathy events was 9%, and there were no grade 4 events.
Eighty-two percent of patients reported resolution or improvement in peripheral neuropathy events in the BV arm at a median of 22.9 months of follow-up.
There were no on-study deaths (occurring within 30 days of the last dose) in the SOC arm, but there were 4 in the BV arm. Three of the BV deaths were considered unrelated to the drug.
The 1 BV-related death was a result of multiple organ dysfunction syndrome attributed to tumor necrosis at visceral disease sites in a patient with T3bN0M1 pcALCL. The other 3 deaths were due to lymphoma progression, pulmonary embolism, and sepsis.
Photo by Larry Young
SAN FRANCISCO—The phase 3 ALCANZA trial is the first to convincingly demonstrate that a new systemic agent can be more effective than standard of care (SOC) options for cutaneous T-cell lymphoma (CTCL), according to a speaker at the 9th Annual T-cell Lymphoma Forum.
The trial showed significant improvements in response, symptom burden, and progression-free survival (PFS) in patients with CD30-expressing CTCL who received brentuximab vedotin (BV), as compared to patients who received either bexarotene or methotrexate.
“[These are] compelling results that potentially may have practice-changing implications for the use of brentuximab in managing CD30-expressing CTCL patients who require systemic therapy,” said Youn H. Kim, MD, of Stanford University School of Medicine in California.
Dr Kim presented these results at this year’s T-cell Lymphoma Forum. The data were also presented at the recent ASH Annual Meeting (abstract 182).
The ALCANZA trial was sponsored by Millennium Pharmaceuticals, Inc. (now a part of Takeda Pharmaceutical Company Limited) and Seattle Genetics, Inc.
The study was designed to compare BV to the SOC options of methotrexate or bexarotene in patients with CD30-positive CTCL, including mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL).
There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg IV every 3 weeks for up to 48 weeks.
The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive methotrexate at 5 mg to 50 mg PO weekly or bexarotene at a target dose of 300 mg/m² PO daily for up to 48 weeks.
Patients received BV for a median of 36 weeks (12 cycles), bexarotene for a median of 17 weeks, and methotrexate for a median of 9 weeks. Three patients in the BV arm were still on treatment at the time of analysis.
Patient characteristics
The median age was 62 (range, 22-83) in the BV am and 59 (range, 22-83) in the SOC arm. More than half of patients in each arm were male—52% and 58%, respectively. And most patients in both arms had an ECOG performance status of 0-1—95% and 97%, respectively.
The median number of prior therapies was 4 (range, 0-13) in the BV arm and 3.5 (range, 1-15) in the SOC arm. The median number of systemic therapies was 2 in the BV arm (range, 0-11) and the SOC arm (range, 1-8).
“It was pretty well balanced in terms of baseline characteristics between the 2 arms,” Dr Kim said. “The brentuximab arm had more stage IV patients—in fact, 7 stage IVB in brentuximab and none in the standard of care. And more patients with ALCL [treated with BV] had extracutaneous disease.”
Among pcALCL patients, 44% in the BV arm had extracutaneous disease, compared to 27% in the SOC arm. Among MF patients, 67% in the BV arm had stage IIB-IVB disease, compared to 61% in the SOC arm.
Response
The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4).
“[ORR4] was felt to be more meaningful than ORR because it includes not only the response rate but also a duration element in a single endpoint,” Dr Kim said.
ORR4 was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).
For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.
Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).
For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.
Symptoms
“In CTCL, there’s significant quality of life issues that are not captured adequately by objective response measures, and this patient outcome is very important,” Dr Kim said. “[Quality of life in this study] was captured by Skindex-29, which is an established quality of life measure in skin diseases.”
Patients in the BV arm had a significantly higher reduction in symptom burden according to Skindex-29 than patients receiving SOC. The mean maximum reduction in Skindex-29 symptom domain was -27.96 points in the BV arm and -8.62 points in the SOC arm (P<0.0001).
PFS
PFS was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).
For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.
Safety
The overall rate of adverse events (AEs) was 95% in the BV arm and 90% in the SOC arm. The rate of grade 3 or higher AEs was 41% and 47%, respectively. And the rate of serious AEs was 29% in both arms.
AEs resulting in discontinuation occurred in 24% of patients in the BV arm and 8% in the SOC arm. In the BV arm, this included peripheral neuropathy (n=9), skin-related hypersensitivity (n=3), E coli infection (n=1), impetigo (n=1), pulmonary embolism (n=1), urticaria (n=1), and vertigo (n=1).
In the SOC arm, AEs leading to discontinuation included maculo-papular rash (n=1), asthenia (n=1), hematuria (n=1), hypernatremia (n=1), neutropenia (n=1), periorbital infection (n=1), and somnolence (n=1). One patient in each arm experienced more than 1 AE resulting in discontinuation.
The most common AEs of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).
The majority of the peripheral neuropathy events in the BV arm were grade 1 or 2—26% and 32%, respectively. The rate of grade 3 peripheral neuropathy events was 9%, and there were no grade 4 events.
Eighty-two percent of patients reported resolution or improvement in peripheral neuropathy events in the BV arm at a median of 22.9 months of follow-up.
There were no on-study deaths (occurring within 30 days of the last dose) in the SOC arm, but there were 4 in the BV arm. Three of the BV deaths were considered unrelated to the drug.
The 1 BV-related death was a result of multiple organ dysfunction syndrome attributed to tumor necrosis at visceral disease sites in a patient with T3bN0M1 pcALCL. The other 3 deaths were due to lymphoma progression, pulmonary embolism, and sepsis.