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Patients with double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) have inferior outcomes after undergoing autologous stem cell transplantation (ASCT), according to a new study published in the Journal of Clinical Oncology.
The worst outcomes were observed in patients with concurrent DELs and DHLs, and this “supports the concept that the double-hit/double-expressor biology appears to render DLBCL resistant to and less likely to be cured by chemotherapy,” write Alex Herrera, MD, an oncologist at the City of Hope, Duarte, Calif., and his colleagues.
But that said, a significant proportion of patients with relapsed/refractory DEL did experience durable remissions following ASCT, particularly those with isolated DEL without DHL.
This suggests that “the presence of DEL alone should not be considered a contraindication to ASCT,” the authors wrote (J Clin Oncol. 2016 Oct. 24. doi: 10.1200/JCO.2016.68.2740).
DHLs and DELs are subtypes of diffuse large B-cell lymphoma (DLBCL), and while they are associated with poor outcomes after standard chemoimmunotherapy, data remain limited as to outcomes of patients with relapsed or refractory disease who undergo ASCT.
The retrospective multicenter study included 117 patients with chemotherapy-sensitive relapsed/refractory DLBCL who underwent ASCT and had archival tumor material available. DEL with MYC/BCL2 coexpression was observed in 52 patients (44%) while 15 patients expressed MYC-R (13%), of whom 12 (10%) had DHL.
The median follow-up time was 45 months for survivors, and the 4-year progression-free survival (PFS) and overall survival (OS) were 54% for the entire cohort.
The 4-year PFS and OS in patients with DHL was worse as compared to those without DHL; 28% vs. 57% (P = .013), and 25% vs. 66% (P less than .001), respectively.
Those with DHL had poorer PFS (28%) and OS (25%), compared with patients with DEL but not DHL (PFS, 53% and OS, 61%) as well as patients with neither DEL nor DHL (PFS, 60% and OS, 70%; three-way P value for PFS, P = .013; OS, P = .002).
Patients with concurrent DEL and DHL had the poorest outcome, with a 4-year PFS of 0%.
After researchers adjusted for clinical characteristics, the only factors that remained significantly associated with PFS were DEL (hazard ratio, 1.8; P = .035) and DHL (HR, 2.9; P = .009). Factors that were significantly associated with OS were DHL (HR, 3.4; P = .004) and remission status at ASCT (HR for partial response, 2.4; P = .007).
Overall, patients with DHL were less likely to achieve a complete response following salvage therapy, and those with DEL and patients with DHL had a shorter time to relapse after induction therapy.
“Although some patients with relapsed/refractory DHL had long-term remission after ASCT (isolated DHL without DEL), the low survival rate in this group argues that alternative transplantation strategies, including allogeneic hematopoietic stem cell transplantation or peri-ASCT relapse prevention strategies should be studied,” they concluded.
Recognizing that the majority of patients with double-hit or double-expressor lymphoma will relapse after R-CHOP, this study evaluates the efficacy of autologous stem cell transplantation as a salvage modality. This is a carefully conducted, albeit retrospective, analysis of patients with relapsed or refractory double-hit or double-expressor lymphoma undergoing autologous hematopoietic stem cell transplantation (auto-HCT) at two high-volume institutions.
Although it is perhaps not surprising that double-hit and double-expressor phenotypes confer inferior outcomes, it is worth examining these issues in some detail. The first issue is that the authors have defined categories that are not recognized by the World Health Organization, but are routinely seen in clinical practice.
For example, it might be assumed that all patients with double-hit lymphoma will have MYC/BCL2 protein expression and, therefore, also have double-expressor lymphoma, but some patients with double-hit lymphoma do not have protein expression of MYC/BCL2 and these patients may have better outcomes than patients whose tumors display both double-hit and double-expressor characteristics.
A second caveat to interpreting the results is that the study population does not reflect the true denominator of all patients with relapsed diffuse large B-cell lymphoma, because only chemotherapy-sensitive patients undergoing auto-HCT were included.
So, should patients with relapsed double-hit and double-expressor lymphoma be offered auto-HCT? What are the alternatives to auto-HCT? Unfortunately, there are no clear answers to these questions, although the surprisingly excellent outcomes for patients without either of these features (70% long-term survival) suggest that there is a group of patients for whom auto-HCT remains an effective and standard tool. For double-hit and double-expressor lymphoma, a clinical trial based on specific biologic changes in individual patients is the ideal but is far from reality at this point.
Overall, despite being a retrospective series with a high attrition rate based on tissue availability, the central review of pathology, uniform assessment of double-hit and double-expressor features, and mature follow-up of 45 months makes this a thought-provoking and timely paper.
Sonali M. Smith, MD, is from the University of Chicago, and has disclosed a consulting or advisory role with Genentech, Seattle Genetics, TG Therapeutics, Gilead Sciences, Immunogenix, Pharmacyclics, NanoString Technologies, Genmab, Juno Therapeutics, Abbvie, and Portola Pharmaceuticals. These remarks were taken from the editorial accompanying Dr. Herrara’s report (J Clin Oncol. 2016 Oct 17. doi: 10.1200/JCO.2016.70.0625).
Recognizing that the majority of patients with double-hit or double-expressor lymphoma will relapse after R-CHOP, this study evaluates the efficacy of autologous stem cell transplantation as a salvage modality. This is a carefully conducted, albeit retrospective, analysis of patients with relapsed or refractory double-hit or double-expressor lymphoma undergoing autologous hematopoietic stem cell transplantation (auto-HCT) at two high-volume institutions.
Although it is perhaps not surprising that double-hit and double-expressor phenotypes confer inferior outcomes, it is worth examining these issues in some detail. The first issue is that the authors have defined categories that are not recognized by the World Health Organization, but are routinely seen in clinical practice.
For example, it might be assumed that all patients with double-hit lymphoma will have MYC/BCL2 protein expression and, therefore, also have double-expressor lymphoma, but some patients with double-hit lymphoma do not have protein expression of MYC/BCL2 and these patients may have better outcomes than patients whose tumors display both double-hit and double-expressor characteristics.
A second caveat to interpreting the results is that the study population does not reflect the true denominator of all patients with relapsed diffuse large B-cell lymphoma, because only chemotherapy-sensitive patients undergoing auto-HCT were included.
So, should patients with relapsed double-hit and double-expressor lymphoma be offered auto-HCT? What are the alternatives to auto-HCT? Unfortunately, there are no clear answers to these questions, although the surprisingly excellent outcomes for patients without either of these features (70% long-term survival) suggest that there is a group of patients for whom auto-HCT remains an effective and standard tool. For double-hit and double-expressor lymphoma, a clinical trial based on specific biologic changes in individual patients is the ideal but is far from reality at this point.
Overall, despite being a retrospective series with a high attrition rate based on tissue availability, the central review of pathology, uniform assessment of double-hit and double-expressor features, and mature follow-up of 45 months makes this a thought-provoking and timely paper.
Sonali M. Smith, MD, is from the University of Chicago, and has disclosed a consulting or advisory role with Genentech, Seattle Genetics, TG Therapeutics, Gilead Sciences, Immunogenix, Pharmacyclics, NanoString Technologies, Genmab, Juno Therapeutics, Abbvie, and Portola Pharmaceuticals. These remarks were taken from the editorial accompanying Dr. Herrara’s report (J Clin Oncol. 2016 Oct 17. doi: 10.1200/JCO.2016.70.0625).
Recognizing that the majority of patients with double-hit or double-expressor lymphoma will relapse after R-CHOP, this study evaluates the efficacy of autologous stem cell transplantation as a salvage modality. This is a carefully conducted, albeit retrospective, analysis of patients with relapsed or refractory double-hit or double-expressor lymphoma undergoing autologous hematopoietic stem cell transplantation (auto-HCT) at two high-volume institutions.
Although it is perhaps not surprising that double-hit and double-expressor phenotypes confer inferior outcomes, it is worth examining these issues in some detail. The first issue is that the authors have defined categories that are not recognized by the World Health Organization, but are routinely seen in clinical practice.
For example, it might be assumed that all patients with double-hit lymphoma will have MYC/BCL2 protein expression and, therefore, also have double-expressor lymphoma, but some patients with double-hit lymphoma do not have protein expression of MYC/BCL2 and these patients may have better outcomes than patients whose tumors display both double-hit and double-expressor characteristics.
A second caveat to interpreting the results is that the study population does not reflect the true denominator of all patients with relapsed diffuse large B-cell lymphoma, because only chemotherapy-sensitive patients undergoing auto-HCT were included.
So, should patients with relapsed double-hit and double-expressor lymphoma be offered auto-HCT? What are the alternatives to auto-HCT? Unfortunately, there are no clear answers to these questions, although the surprisingly excellent outcomes for patients without either of these features (70% long-term survival) suggest that there is a group of patients for whom auto-HCT remains an effective and standard tool. For double-hit and double-expressor lymphoma, a clinical trial based on specific biologic changes in individual patients is the ideal but is far from reality at this point.
Overall, despite being a retrospective series with a high attrition rate based on tissue availability, the central review of pathology, uniform assessment of double-hit and double-expressor features, and mature follow-up of 45 months makes this a thought-provoking and timely paper.
Sonali M. Smith, MD, is from the University of Chicago, and has disclosed a consulting or advisory role with Genentech, Seattle Genetics, TG Therapeutics, Gilead Sciences, Immunogenix, Pharmacyclics, NanoString Technologies, Genmab, Juno Therapeutics, Abbvie, and Portola Pharmaceuticals. These remarks were taken from the editorial accompanying Dr. Herrara’s report (J Clin Oncol. 2016 Oct 17. doi: 10.1200/JCO.2016.70.0625).
Patients with double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) have inferior outcomes after undergoing autologous stem cell transplantation (ASCT), according to a new study published in the Journal of Clinical Oncology.
The worst outcomes were observed in patients with concurrent DELs and DHLs, and this “supports the concept that the double-hit/double-expressor biology appears to render DLBCL resistant to and less likely to be cured by chemotherapy,” write Alex Herrera, MD, an oncologist at the City of Hope, Duarte, Calif., and his colleagues.
But that said, a significant proportion of patients with relapsed/refractory DEL did experience durable remissions following ASCT, particularly those with isolated DEL without DHL.
This suggests that “the presence of DEL alone should not be considered a contraindication to ASCT,” the authors wrote (J Clin Oncol. 2016 Oct. 24. doi: 10.1200/JCO.2016.68.2740).
DHLs and DELs are subtypes of diffuse large B-cell lymphoma (DLBCL), and while they are associated with poor outcomes after standard chemoimmunotherapy, data remain limited as to outcomes of patients with relapsed or refractory disease who undergo ASCT.
The retrospective multicenter study included 117 patients with chemotherapy-sensitive relapsed/refractory DLBCL who underwent ASCT and had archival tumor material available. DEL with MYC/BCL2 coexpression was observed in 52 patients (44%) while 15 patients expressed MYC-R (13%), of whom 12 (10%) had DHL.
The median follow-up time was 45 months for survivors, and the 4-year progression-free survival (PFS) and overall survival (OS) were 54% for the entire cohort.
The 4-year PFS and OS in patients with DHL was worse as compared to those without DHL; 28% vs. 57% (P = .013), and 25% vs. 66% (P less than .001), respectively.
Those with DHL had poorer PFS (28%) and OS (25%), compared with patients with DEL but not DHL (PFS, 53% and OS, 61%) as well as patients with neither DEL nor DHL (PFS, 60% and OS, 70%; three-way P value for PFS, P = .013; OS, P = .002).
Patients with concurrent DEL and DHL had the poorest outcome, with a 4-year PFS of 0%.
After researchers adjusted for clinical characteristics, the only factors that remained significantly associated with PFS were DEL (hazard ratio, 1.8; P = .035) and DHL (HR, 2.9; P = .009). Factors that were significantly associated with OS were DHL (HR, 3.4; P = .004) and remission status at ASCT (HR for partial response, 2.4; P = .007).
Overall, patients with DHL were less likely to achieve a complete response following salvage therapy, and those with DEL and patients with DHL had a shorter time to relapse after induction therapy.
“Although some patients with relapsed/refractory DHL had long-term remission after ASCT (isolated DHL without DEL), the low survival rate in this group argues that alternative transplantation strategies, including allogeneic hematopoietic stem cell transplantation or peri-ASCT relapse prevention strategies should be studied,” they concluded.
Patients with double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) have inferior outcomes after undergoing autologous stem cell transplantation (ASCT), according to a new study published in the Journal of Clinical Oncology.
The worst outcomes were observed in patients with concurrent DELs and DHLs, and this “supports the concept that the double-hit/double-expressor biology appears to render DLBCL resistant to and less likely to be cured by chemotherapy,” write Alex Herrera, MD, an oncologist at the City of Hope, Duarte, Calif., and his colleagues.
But that said, a significant proportion of patients with relapsed/refractory DEL did experience durable remissions following ASCT, particularly those with isolated DEL without DHL.
This suggests that “the presence of DEL alone should not be considered a contraindication to ASCT,” the authors wrote (J Clin Oncol. 2016 Oct. 24. doi: 10.1200/JCO.2016.68.2740).
DHLs and DELs are subtypes of diffuse large B-cell lymphoma (DLBCL), and while they are associated with poor outcomes after standard chemoimmunotherapy, data remain limited as to outcomes of patients with relapsed or refractory disease who undergo ASCT.
The retrospective multicenter study included 117 patients with chemotherapy-sensitive relapsed/refractory DLBCL who underwent ASCT and had archival tumor material available. DEL with MYC/BCL2 coexpression was observed in 52 patients (44%) while 15 patients expressed MYC-R (13%), of whom 12 (10%) had DHL.
The median follow-up time was 45 months for survivors, and the 4-year progression-free survival (PFS) and overall survival (OS) were 54% for the entire cohort.
The 4-year PFS and OS in patients with DHL was worse as compared to those without DHL; 28% vs. 57% (P = .013), and 25% vs. 66% (P less than .001), respectively.
Those with DHL had poorer PFS (28%) and OS (25%), compared with patients with DEL but not DHL (PFS, 53% and OS, 61%) as well as patients with neither DEL nor DHL (PFS, 60% and OS, 70%; three-way P value for PFS, P = .013; OS, P = .002).
Patients with concurrent DEL and DHL had the poorest outcome, with a 4-year PFS of 0%.
After researchers adjusted for clinical characteristics, the only factors that remained significantly associated with PFS were DEL (hazard ratio, 1.8; P = .035) and DHL (HR, 2.9; P = .009). Factors that were significantly associated with OS were DHL (HR, 3.4; P = .004) and remission status at ASCT (HR for partial response, 2.4; P = .007).
Overall, patients with DHL were less likely to achieve a complete response following salvage therapy, and those with DEL and patients with DHL had a shorter time to relapse after induction therapy.
“Although some patients with relapsed/refractory DHL had long-term remission after ASCT (isolated DHL without DEL), the low survival rate in this group argues that alternative transplantation strategies, including allogeneic hematopoietic stem cell transplantation or peri-ASCT relapse prevention strategies should be studied,” they concluded.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: The 4-year progression-free survival in patients with DEL vs. non-DEL was 48% versus 59% (P = .049), and the 4-year OS was 56% vs. 67% (P = .10).
Data source: Retrospective, multicenter study that included 117 patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who underwent ASCT.
Disclosures: The study was funded by a Conquer Cancer Foundation/ASCO Young Investigator Award and National Cancer Institute Grants; the Dana-Farber Cancer Institute Award Fund for Collaborative Research Initiatives in Hematologic Oncology; the Harold and Virginia Lash/David Lash Fund for Lymphoma Research; and NCI Grant No. P30CA033572 for work performed in the COH Pathology Core. Dr. Herrera reports receiving research funding from Seattle Genetics, Pharmacyclics, Genentech, Immune Design, and Sequenta, and received travel, accommodations, and expenses from Bristol-Myers Squibb. Several coauthors also report relationships with industry.