Non-Hodgkin Lymphoma Hub

Autologous stem-cell transplantation can be highly effective in securing better long-term results for patients undergoing rituximab-based chemotherapy for transformed indolent lymphoma with high-grade histologies, according to a retrospective study published online in Annals of Oncology.

ASCT improved outcomes in patients with sequential TIL (S-TIL), but not in those with composite/discordant TIL (CD-TIL). The benefits of ASCT were greater in patients who were rituximab-naive at transformation, wrote Dr. Carsten Madsen of Denmark’s Aarhus University Hospital, and his coauthors (Ann. Oncol. 2014 Nov. 18 [doi: 10.1093/annonc/mdu537]).

Patients with “CD-TIL had a better outcome than [did those with] S-TIL regardless of treatment strategy at transformation. With regard to ASCT in particular, we found that it had a beneficial influence on outcome limited to S-TIL,” the investigators concluded.

In a multicenter cohort study, Dr. Madsen and his associates used the National Danish Pathology Registry to identify patients aged 18-68 years with histologically verified TIL diagnosed between 1999 and 2012 at the Aarhus, Odense, and Aalborg university hospitals in Denmark. Researchers looked for TIL, defined as “a biopsy proven IL in addition to a DLBCL [diffuse large B-cell lymphoma] lesion that was either coexisting at primary diagnosis or histologically ascertained over time through a subsequent biopsy.” In total, 85 patients were selected for the study – 72 subjects with follicular lymphoma at histological grades between 1 and 3A, and 13 subjects with otherwise unspecified forms of indolent lymphoma (IL).

Data for all patients were used to calculate 5-year overall survival (OS) and progression-free survival (PFS) rates. Calculations were done in three cohorts: an “all TIL” whole cohort, a CD-TIL cohort of subjects with “coexisting evidence of both indolent and aggressive histology at diagnosis,” and an S-TIL cohort of subjects who transformed after having indolent lymphoma for a prolonged period of time.

Of the 85 subjects, 54 (64%) received ASCT consolidation and 31 (36%) did not.

In the “all TIL” cohort, the OS and PFS rates were higher in subjects who received rituximab-containing regimens and ASCT compared with those who received only the chemotherapy. The OS rates were 67% vs. 48% (P = .11); the PFS rates were 60% versus 30% (P = .02).

There was no evidence of an advantage in the CD-TIL cohort, the OS rates were 76% for the combined therapy versus 67% for those given rituximab-based chemo only (P = .66), and the PFS rates were 71% versus 36% (P = .54).

The sequential TIL cohort, however, saw improvements in both OS and PFS – 62% versus 36% (P = .07) and 53% versus 6% (P = .002), respectively – regardless of whether or not patients had previously received rituximab-based chemo.

Prospective clinical trials, specifically designed for TIL patients, should be encouraged to investigate the optimal treatment strategy for this still largely unmet clinical need, the researchers concluded.

The authors disclosed no conflicts of interest.

dchitnis@frontlinemedcom.com

Autologous stem-cell transplantation can be highly effective in securing better long-term results for patients undergoing rituximab-based chemotherapy for transformed indolent lymphoma with high-grade histologies, according to a retrospective study published online in Annals of Oncology.

ASCT improved outcomes in patients with sequential TIL (S-TIL), but not in those with composite/discordant TIL (CD-TIL). The benefits of ASCT were greater in patients who were rituximab-naive at transformation, wrote Dr. Carsten Madsen of Denmark’s Aarhus University Hospital, and his coauthors (Ann. Oncol. 2014 Nov. 18 [doi: 10.1093/annonc/mdu537]).

Patients with “CD-TIL had a better outcome than [did those with] S-TIL regardless of treatment strategy at transformation. With regard to ASCT in particular, we found that it had a beneficial influence on outcome limited to S-TIL,” the investigators concluded.

In a multicenter cohort study, Dr. Madsen and his associates used the National Danish Pathology Registry to identify patients aged 18-68 years with histologically verified TIL diagnosed between 1999 and 2012 at the Aarhus, Odense, and Aalborg university hospitals in Denmark. Researchers looked for TIL, defined as “a biopsy proven IL in addition to a DLBCL [diffuse large B-cell lymphoma] lesion that was either coexisting at primary diagnosis or histologically ascertained over time through a subsequent biopsy.” In total, 85 patients were selected for the study – 72 subjects with follicular lymphoma at histological grades between 1 and 3A, and 13 subjects with otherwise unspecified forms of indolent lymphoma (IL).

Data for all patients were used to calculate 5-year overall survival (OS) and progression-free survival (PFS) rates. Calculations were done in three cohorts: an “all TIL” whole cohort, a CD-TIL cohort of subjects with “coexisting evidence of both indolent and aggressive histology at diagnosis,” and an S-TIL cohort of subjects who transformed after having indolent lymphoma for a prolonged period of time.

Of the 85 subjects, 54 (64%) received ASCT consolidation and 31 (36%) did not.

In the “all TIL” cohort, the OS and PFS rates were higher in subjects who received rituximab-containing regimens and ASCT compared with those who received only the chemotherapy. The OS rates were 67% vs. 48% (P = .11); the PFS rates were 60% versus 30% (P = .02).

There was no evidence of an advantage in the CD-TIL cohort, the OS rates were 76% for the combined therapy versus 67% for those given rituximab-based chemo only (P = .66), and the PFS rates were 71% versus 36% (P = .54).

The sequential TIL cohort, however, saw improvements in both OS and PFS – 62% versus 36% (P = .07) and 53% versus 6% (P = .002), respectively – regardless of whether or not patients had previously received rituximab-based chemo.

Prospective clinical trials, specifically designed for TIL patients, should be encouraged to investigate the optimal treatment strategy for this still largely unmet clinical need, the researchers concluded.

The authors disclosed no conflicts of interest.

dchitnis@frontlinemedcom.com

Autologous stem-cell transplantation can be highly effective in securing better long-term results for patients undergoing rituximab-based chemotherapy for transformed indolent lymphoma with high-grade histologies, according to a retrospective study published online in Annals of Oncology.

ASCT improved outcomes in patients with sequential TIL (S-TIL), but not in those with composite/discordant TIL (CD-TIL). The benefits of ASCT were greater in patients who were rituximab-naive at transformation, wrote Dr. Carsten Madsen of Denmark’s Aarhus University Hospital, and his coauthors (Ann. Oncol. 2014 Nov. 18 [doi: 10.1093/annonc/mdu537]).

Patients with “CD-TIL had a better outcome than [did those with] S-TIL regardless of treatment strategy at transformation. With regard to ASCT in particular, we found that it had a beneficial influence on outcome limited to S-TIL,” the investigators concluded.

In a multicenter cohort study, Dr. Madsen and his associates used the National Danish Pathology Registry to identify patients aged 18-68 years with histologically verified TIL diagnosed between 1999 and 2012 at the Aarhus, Odense, and Aalborg university hospitals in Denmark. Researchers looked for TIL, defined as “a biopsy proven IL in addition to a DLBCL [diffuse large B-cell lymphoma] lesion that was either coexisting at primary diagnosis or histologically ascertained over time through a subsequent biopsy.” In total, 85 patients were selected for the study – 72 subjects with follicular lymphoma at histological grades between 1 and 3A, and 13 subjects with otherwise unspecified forms of indolent lymphoma (IL).

Data for all patients were used to calculate 5-year overall survival (OS) and progression-free survival (PFS) rates. Calculations were done in three cohorts: an “all TIL” whole cohort, a CD-TIL cohort of subjects with “coexisting evidence of both indolent and aggressive histology at diagnosis,” and an S-TIL cohort of subjects who transformed after having indolent lymphoma for a prolonged period of time.

Of the 85 subjects, 54 (64%) received ASCT consolidation and 31 (36%) did not.

In the “all TIL” cohort, the OS and PFS rates were higher in subjects who received rituximab-containing regimens and ASCT compared with those who received only the chemotherapy. The OS rates were 67% vs. 48% (P = .11); the PFS rates were 60% versus 30% (P = .02).

There was no evidence of an advantage in the CD-TIL cohort, the OS rates were 76% for the combined therapy versus 67% for those given rituximab-based chemo only (P = .66), and the PFS rates were 71% versus 36% (P = .54).

The sequential TIL cohort, however, saw improvements in both OS and PFS – 62% versus 36% (P = .07) and 53% versus 6% (P = .002), respectively – regardless of whether or not patients had previously received rituximab-based chemo.

Prospective clinical trials, specifically designed for TIL patients, should be encouraged to investigate the optimal treatment strategy for this still largely unmet clinical need, the researchers concluded.

The authors disclosed no conflicts of interest.

dchitnis@frontlinemedcom.com

SAN FRANCISCO – Early post-transplant brentuximab vedotin dramatically slows Hodgkin’s lymphoma progression in patients at high risk for relapse or progression, the phase III AETHERA study shows.

After a median follow-up of about 28 months, the primary end point of progression-free survival (PFS) per independent review increased from a median of 24 months with placebo and best supportive care (BSC) to 43 months with brentuximab and BSC (Hazard ratio, 0.57; P = .001).

Per investigator assessment, median PFS was 16 months with placebo and had not been reached with brentuximab (HR, 0.50),Dr. Craig Moskowitz reported at the annual meeting of the American Society of Hematology.

Patrice Wendling/Frontline Medical News

The benefit of brentuximab maintenance was consistent across every subgroup. Historically, roughly half of patients who undergo an autologous stem cell transplant will relapse.

“Once this study is published, in patients who met eligibility criteria to be on this study - and once again I’ll remind you that’s remission duration less than one year, disease outside the lymph node system, or primary refractory disease - in my opinion, this will be the standard of care,” Dr. Moskowitz said during a press briefing.

Brentuximab, an anti-CD30 antibody conjugate, is already approved in the U.S. for the management of Hodgkin’s lymphoma (HL) after failure of autologous stem cell transplantation (ASCT) or at least two prior lines of multi-agent chemotherapy in patients ineligible for ASCT.

Brentuximab is also indicated for systemic anaplastic large cell lymphoma after failure of at least one multi-agent chemotherapy regimen.

In September it was announced that AETHERA met its primary end point, but this was the first full look at the absolute survival rates and safety data.

The 2-year PFS rate for the brentuximab and placebo groups is now 63% vs. 51% per independent review and 65% vs. 45% per investigator.

“The bottom line is there’s a 20% difference in progression-free survival at 2 years upon investigator review. This has never been seen in patients with relapsed, refractory lymphoma, let alone Hodgkin lymphoma,” Dr. Moskowitz, clinical director of hematology oncology at Memorial Sloan-Kettering Cancer Center in New York City, said.

Overall survival data are immature, but was the same in both groups at 2 years (P = .62). The likelihood of showing a survival difference was not expected because 85% of patients who relapsed on the placebo arm crossed over to brentuximab, as allowed per protocol, and it’s known that brentuximab alone in auto-transplant failures improves outcomes by at least a year, he said. Also, twice as many patients who failed placebo received a second transplant.

Dr. Moskowitz stressed that nearly every patient in the trial had at least three risk factors that would place them at high risk of treatment failure and that studies have shown that for patients with this many risk factors, the chance of being cured by an auto-transplant is about 25%. The risk factors are: relapsed less than 12 months or refractory to frontline therapy, best response of partial remission or stable disease to most recent salvage therapy, extranodal disease at pre-ASCT relapse, B symptoms at pre-ASCT relapse, or two or more prior salvage therapies.

Press briefing moderator Dr. Brad Kahl of the University of Wisconsin-Madison, said Aethera is the first study to show a significant benefit for a post-transplant strategy.

“The biggest question in my mind is whether the application of maintenance brentuximab vedotin is just delaying the inevitable relapse, so the patients will still relapse, just later, or has the brentuximab taken patients who are destined to relapse and turned them into a cured patient,” Dr. Kahl said. “We don’t know the answer to that question. That will become apparent with more time.”

Dr. Moscowitz observed that relapses almost never happen after two year, adding, “So if you’re in remission at two years after stem cell transplantation for Hodgkin lymphoma, you are likely to be cured.”

AETHERA enrolled 329 patients with Hodgkin’s lymphoma and randomly assigned them after ASCT to brentuximab vedotin 1.8 mg/kg or placebo given every 3 weeks for up to 16 cycles, plus BSC. All patients were required to have achieved a complete response, partial remission, or stable disease to salvage therapy prior to ASCT. Their median age was 32 years and 53% were male.

Roughly 60% were refractory to upfront therapy, 43% in the brentuximab arm and 48% of controls had received 2 or more prior systemic therapies, and a third in each arm had extranodal involvement.

Consolidation therapy with brentuximab was generally well tolerated, Dr. Moskowitz said. Peripheral sensory neuropathy was the most common side effect, experienced at any grade in 67% on brentuximab vs. 19% of controls and at grade 3 in 13% vs. 1%. There were no grade 4 events and 85% of patients had resolution or improvement with dose reductions or stopping the drug.

Other adverse events in the brentuximab and control groups were neutropenia (35% vs. 12%), upper respiratory tract infections (26% vs. 23%), and fatigue (24% vs. 18%). Two patients died within 40 days of dosing with brentuximab, one from treatment-related acute respiratory distress syndrome associated with pneumonitis and one following an episode of treatment-related acute pancreatitis that had resolved at the time of death, he reported.

Based on the results, study sponsor Seattle Genetics is expected to seek approval for brentuximab in this consolidation setting in the first half of 2015, according to a statement from the company. The ongoing phase III ECHELON-1 and ECHELON 2 trials in HL and mature T-cell lymphomas are looking at the use of brentuximab in frontline disease.

pwendling@frontlinemedcom.com

SAN FRANCISCO – Early post-transplant brentuximab vedotin dramatically slows Hodgkin’s lymphoma progression in patients at high risk for relapse or progression, the phase III AETHERA study shows.

After a median follow-up of about 28 months, the primary end point of progression-free survival (PFS) per independent review increased from a median of 24 months with placebo and best supportive care (BSC) to 43 months with brentuximab and BSC (Hazard ratio, 0.57; P = .001).

Per investigator assessment, median PFS was 16 months with placebo and had not been reached with brentuximab (HR, 0.50),Dr. Craig Moskowitz reported at the annual meeting of the American Society of Hematology.

Patrice Wendling/Frontline Medical News

The benefit of brentuximab maintenance was consistent across every subgroup. Historically, roughly half of patients who undergo an autologous stem cell transplant will relapse.

“Once this study is published, in patients who met eligibility criteria to be on this study - and once again I’ll remind you that’s remission duration less than one year, disease outside the lymph node system, or primary refractory disease - in my opinion, this will be the standard of care,” Dr. Moskowitz said during a press briefing.

Brentuximab, an anti-CD30 antibody conjugate, is already approved in the U.S. for the management of Hodgkin’s lymphoma (HL) after failure of autologous stem cell transplantation (ASCT) or at least two prior lines of multi-agent chemotherapy in patients ineligible for ASCT.

Brentuximab is also indicated for systemic anaplastic large cell lymphoma after failure of at least one multi-agent chemotherapy regimen.

In September it was announced that AETHERA met its primary end point, but this was the first full look at the absolute survival rates and safety data.

The 2-year PFS rate for the brentuximab and placebo groups is now 63% vs. 51% per independent review and 65% vs. 45% per investigator.

“The bottom line is there’s a 20% difference in progression-free survival at 2 years upon investigator review. This has never been seen in patients with relapsed, refractory lymphoma, let alone Hodgkin lymphoma,” Dr. Moskowitz, clinical director of hematology oncology at Memorial Sloan-Kettering Cancer Center in New York City, said.

Overall survival data are immature, but was the same in both groups at 2 years (P = .62). The likelihood of showing a survival difference was not expected because 85% of patients who relapsed on the placebo arm crossed over to brentuximab, as allowed per protocol, and it’s known that brentuximab alone in auto-transplant failures improves outcomes by at least a year, he said. Also, twice as many patients who failed placebo received a second transplant.

Dr. Moskowitz stressed that nearly every patient in the trial had at least three risk factors that would place them at high risk of treatment failure and that studies have shown that for patients with this many risk factors, the chance of being cured by an auto-transplant is about 25%. The risk factors are: relapsed less than 12 months or refractory to frontline therapy, best response of partial remission or stable disease to most recent salvage therapy, extranodal disease at pre-ASCT relapse, B symptoms at pre-ASCT relapse, or two or more prior salvage therapies.

Press briefing moderator Dr. Brad Kahl of the University of Wisconsin-Madison, said Aethera is the first study to show a significant benefit for a post-transplant strategy.

“The biggest question in my mind is whether the application of maintenance brentuximab vedotin is just delaying the inevitable relapse, so the patients will still relapse, just later, or has the brentuximab taken patients who are destined to relapse and turned them into a cured patient,” Dr. Kahl said. “We don’t know the answer to that question. That will become apparent with more time.”

Dr. Moscowitz observed that relapses almost never happen after two year, adding, “So if you’re in remission at two years after stem cell transplantation for Hodgkin lymphoma, you are likely to be cured.”

AETHERA enrolled 329 patients with Hodgkin’s lymphoma and randomly assigned them after ASCT to brentuximab vedotin 1.8 mg/kg or placebo given every 3 weeks for up to 16 cycles, plus BSC. All patients were required to have achieved a complete response, partial remission, or stable disease to salvage therapy prior to ASCT. Their median age was 32 years and 53% were male.

Roughly 60% were refractory to upfront therapy, 43% in the brentuximab arm and 48% of controls had received 2 or more prior systemic therapies, and a third in each arm had extranodal involvement.

Consolidation therapy with brentuximab was generally well tolerated, Dr. Moskowitz said. Peripheral sensory neuropathy was the most common side effect, experienced at any grade in 67% on brentuximab vs. 19% of controls and at grade 3 in 13% vs. 1%. There were no grade 4 events and 85% of patients had resolution or improvement with dose reductions or stopping the drug.

Other adverse events in the brentuximab and control groups were neutropenia (35% vs. 12%), upper respiratory tract infections (26% vs. 23%), and fatigue (24% vs. 18%). Two patients died within 40 days of dosing with brentuximab, one from treatment-related acute respiratory distress syndrome associated with pneumonitis and one following an episode of treatment-related acute pancreatitis that had resolved at the time of death, he reported.

Based on the results, study sponsor Seattle Genetics is expected to seek approval for brentuximab in this consolidation setting in the first half of 2015, according to a statement from the company. The ongoing phase III ECHELON-1 and ECHELON 2 trials in HL and mature T-cell lymphomas are looking at the use of brentuximab in frontline disease.

pwendling@frontlinemedcom.com

SAN FRANCISCO – Early post-transplant brentuximab vedotin dramatically slows Hodgkin’s lymphoma progression in patients at high risk for relapse or progression, the phase III AETHERA study shows.

After a median follow-up of about 28 months, the primary end point of progression-free survival (PFS) per independent review increased from a median of 24 months with placebo and best supportive care (BSC) to 43 months with brentuximab and BSC (Hazard ratio, 0.57; P = .001).

Per investigator assessment, median PFS was 16 months with placebo and had not been reached with brentuximab (HR, 0.50),Dr. Craig Moskowitz reported at the annual meeting of the American Society of Hematology.

Patrice Wendling/Frontline Medical News

The benefit of brentuximab maintenance was consistent across every subgroup. Historically, roughly half of patients who undergo an autologous stem cell transplant will relapse.

“Once this study is published, in patients who met eligibility criteria to be on this study - and once again I’ll remind you that’s remission duration less than one year, disease outside the lymph node system, or primary refractory disease - in my opinion, this will be the standard of care,” Dr. Moskowitz said during a press briefing.

Brentuximab, an anti-CD30 antibody conjugate, is already approved in the U.S. for the management of Hodgkin’s lymphoma (HL) after failure of autologous stem cell transplantation (ASCT) or at least two prior lines of multi-agent chemotherapy in patients ineligible for ASCT.

Brentuximab is also indicated for systemic anaplastic large cell lymphoma after failure of at least one multi-agent chemotherapy regimen.

In September it was announced that AETHERA met its primary end point, but this was the first full look at the absolute survival rates and safety data.

The 2-year PFS rate for the brentuximab and placebo groups is now 63% vs. 51% per independent review and 65% vs. 45% per investigator.

“The bottom line is there’s a 20% difference in progression-free survival at 2 years upon investigator review. This has never been seen in patients with relapsed, refractory lymphoma, let alone Hodgkin lymphoma,” Dr. Moskowitz, clinical director of hematology oncology at Memorial Sloan-Kettering Cancer Center in New York City, said.

Overall survival data are immature, but was the same in both groups at 2 years (P = .62). The likelihood of showing a survival difference was not expected because 85% of patients who relapsed on the placebo arm crossed over to brentuximab, as allowed per protocol, and it’s known that brentuximab alone in auto-transplant failures improves outcomes by at least a year, he said. Also, twice as many patients who failed placebo received a second transplant.

Dr. Moskowitz stressed that nearly every patient in the trial had at least three risk factors that would place them at high risk of treatment failure and that studies have shown that for patients with this many risk factors, the chance of being cured by an auto-transplant is about 25%. The risk factors are: relapsed less than 12 months or refractory to frontline therapy, best response of partial remission or stable disease to most recent salvage therapy, extranodal disease at pre-ASCT relapse, B symptoms at pre-ASCT relapse, or two or more prior salvage therapies.

Press briefing moderator Dr. Brad Kahl of the University of Wisconsin-Madison, said Aethera is the first study to show a significant benefit for a post-transplant strategy.

“The biggest question in my mind is whether the application of maintenance brentuximab vedotin is just delaying the inevitable relapse, so the patients will still relapse, just later, or has the brentuximab taken patients who are destined to relapse and turned them into a cured patient,” Dr. Kahl said. “We don’t know the answer to that question. That will become apparent with more time.”

Dr. Moscowitz observed that relapses almost never happen after two year, adding, “So if you’re in remission at two years after stem cell transplantation for Hodgkin lymphoma, you are likely to be cured.”

AETHERA enrolled 329 patients with Hodgkin’s lymphoma and randomly assigned them after ASCT to brentuximab vedotin 1.8 mg/kg or placebo given every 3 weeks for up to 16 cycles, plus BSC. All patients were required to have achieved a complete response, partial remission, or stable disease to salvage therapy prior to ASCT. Their median age was 32 years and 53% were male.

Roughly 60% were refractory to upfront therapy, 43% in the brentuximab arm and 48% of controls had received 2 or more prior systemic therapies, and a third in each arm had extranodal involvement.

Consolidation therapy with brentuximab was generally well tolerated, Dr. Moskowitz said. Peripheral sensory neuropathy was the most common side effect, experienced at any grade in 67% on brentuximab vs. 19% of controls and at grade 3 in 13% vs. 1%. There were no grade 4 events and 85% of patients had resolution or improvement with dose reductions or stopping the drug.

Other adverse events in the brentuximab and control groups were neutropenia (35% vs. 12%), upper respiratory tract infections (26% vs. 23%), and fatigue (24% vs. 18%). Two patients died within 40 days of dosing with brentuximab, one from treatment-related acute respiratory distress syndrome associated with pneumonitis and one following an episode of treatment-related acute pancreatitis that had resolved at the time of death, he reported.

Based on the results, study sponsor Seattle Genetics is expected to seek approval for brentuximab in this consolidation setting in the first half of 2015, according to a statement from the company. The ongoing phase III ECHELON-1 and ECHELON 2 trials in HL and mature T-cell lymphomas are looking at the use of brentuximab in frontline disease.

pwendling@frontlinemedcom.com

SAN FRANCISCO– PD-1 checkpoint inhibitors, which have shown remarkable efficacy against advanced malignant melanoma, appear to hold similar promise in the treatment of relapsed or refractory Hodgkin’s lymphoma, results from two early studies suggest.

In a phase I study, the PD-1 blocking antibody nivolumab produced an 87% response rate in 23 heavily pre-treated patients with relapsed Hodgkin’s lymphoma (HL). In a separate phase Ib study, pembrolizumab, which blocks the PD-1 and PD-2 ligands, produced a 66% overall response rate, 21% complete remission rate, and 86% clinical benefit rate among 29 patients with HL for whom therapy with brentuximab vedotin (Adcetris) had failed.

The studies were presented at a media briefing prior to the presentation of data in oral sessions at the annual meeting of the American Society of Hematology.

“Classical Hodgkin lymphoma appears to be a tumor with genetically determined vulnerability to PD-1 blockade. We hope that PD-1 blockade in the future can become an important part of the treatment of patients with Hodgkin lymphoma,” said Dr. Phillipe Armand from the Dana-Farber Cancer Institute in Boston, an investigator for the nivolumab study.

Neil Osterweil/Frontline Medical News

Evidence from preclinical studies suggests that the Reed-Sternberg malignant cells characteristic of HL may use the PD-1 (programmed death 1) pathway to evade detection by immune cells, as suggested by pathologic studies showing the cells surrounded by an extensive but ineffective infiltrate of inflammatory cells.

“We’ve wondered for a long time how Hodgkin lymphoma could attract such a brisk immune response and yet have this immune response fail to kill the tumor,” he said.

Genetic Achilles heel

Genetic analyses had shown that HL frequently has a mutation that results in amplification of a region on chromosome 9 (9p24.1) which leads to increased expression of PD-1 ligands 1 and 2, and leads to a downregulation or weakening of the immune response. The mutation appears to work through the Janus kinase (JAK)-signal transducer and activator transcription (STAT) signalling. These findings suggested to researchers that classical HL has a genetically driven and, ideally, targetable dependence on the PD-1 pathway for survival, Dr. Armand explained.

To test this idea, he and colleagues studied 23 patients with relapsed or refractory HL that had been heavily pre-treated who were part of an independent expansion cohort of a study of nivolumab in hematologic malignancies. Of these patients, 78% were enrolled after a relapse following autologous stem cell transplantation, and 22% after treatment with brentuximab vedotin had failed.

The patients received nivolumab 3 mg/kg every 2 weeks until they had either a complete response, tumor progression, or excessive side effects. In all, 20 of the 23 patients (87%) had an objective response to the single-agent therapy, including 4 (17%) complete responses and 16 (70%) partial responses. The remaining three patients (13%) had stable disease.

The longest time on study at the data cutoff point was 72 weeks. Among all responders, 60% had a response by 8 weeks of therapy, 48% are ongoing, and 43% of patients are still on treatment.

Drug-related adverse events were reported in 18 patients, most commonly rash and decreased platelet count. Five patients had grade 3 events. There were no drug-related grade 4 events or deaths.

In an editorial accompanying the study, which was also published online in The New England Journal of Medicine, Dr. Mario Sznoll and Dr. Dan L. Longo from the Yale University School of Medicine in New Haven, Connecticut write that “with recent data showing impressive clinical activity of PD-1 or PD-L1 antagonists in subgroups of patients with a variety of different cancers, the critical and foundational role of immune interventions in cancer treatment is no longer deniable,” (NEJM, Dec. 6, 2014 [DOI: 10.1056/NEJMoa1411087]).

Pembrolizumab trial

Dr. Craig H. Moskowitz from Memorial Sloan-Kettering Cancer Center in New York City discussed results of the second study, dubbed KEYNOTE-013 (A Phase Ib Multi-Cohort Trial of MK-3475 in Subjects With Hematologic Malignancies).

In this study, patients with HL who were not transplant eligible or for whom transplant had failed and who either had a relapse or were refractory to therapy with brentuximab vedotin received 19 mg/kg IV infusion of pembrolizumab every 2 weeks until complete response, partial response/stable disease, or disease progression.

Of the 31 patients enrolled, 29 were available for the analysis. As of the data cutoff in November 2014, 6 patients (21%) had achieved a complete remission, and 13 (45%) had a partial response, for an overall response rate of 66%. The median time to response was 12 weeks, and as of the data cutoff 17 of 19 patients had ongoing responses. The median response duration has not yet been reached. An additional 6 patients (21%) had stable disease, leading to an overall clinical benefit rate (responses plus stable disease) of 86%.

The patients generally tolerated the drug well. There were 4 treatment-related adverse events in 3 patients, including axillary pain, hypoxia, joint swelling, and pneumonitis. There were no grade 4 treatment-related events or deaths.

Of the tumor samples evaluable, all expressed PD-L1, supporting the rationale for PD-1 blockade in this population, Dr. Moskowitz said.

The results of both his and Dr. Armand’s study support the continued development of PD-1 inhibitors in various subsets of patients with classical Hodgkin’s lymphoma, he said.

SAN FRANCISCO– PD-1 checkpoint inhibitors, which have shown remarkable efficacy against advanced malignant melanoma, appear to hold similar promise in the treatment of relapsed or refractory Hodgkin’s lymphoma, results from two early studies suggest.

In a phase I study, the PD-1 blocking antibody nivolumab produced an 87% response rate in 23 heavily pre-treated patients with relapsed Hodgkin’s lymphoma (HL). In a separate phase Ib study, pembrolizumab, which blocks the PD-1 and PD-2 ligands, produced a 66% overall response rate, 21% complete remission rate, and 86% clinical benefit rate among 29 patients with HL for whom therapy with brentuximab vedotin (Adcetris) had failed.

The studies were presented at a media briefing prior to the presentation of data in oral sessions at the annual meeting of the American Society of Hematology.

“Classical Hodgkin lymphoma appears to be a tumor with genetically determined vulnerability to PD-1 blockade. We hope that PD-1 blockade in the future can become an important part of the treatment of patients with Hodgkin lymphoma,” said Dr. Phillipe Armand from the Dana-Farber Cancer Institute in Boston, an investigator for the nivolumab study.

Neil Osterweil/Frontline Medical News

Evidence from preclinical studies suggests that the Reed-Sternberg malignant cells characteristic of HL may use the PD-1 (programmed death 1) pathway to evade detection by immune cells, as suggested by pathologic studies showing the cells surrounded by an extensive but ineffective infiltrate of inflammatory cells.

“We’ve wondered for a long time how Hodgkin lymphoma could attract such a brisk immune response and yet have this immune response fail to kill the tumor,” he said.

Genetic Achilles heel

Genetic analyses had shown that HL frequently has a mutation that results in amplification of a region on chromosome 9 (9p24.1) which leads to increased expression of PD-1 ligands 1 and 2, and leads to a downregulation or weakening of the immune response. The mutation appears to work through the Janus kinase (JAK)-signal transducer and activator transcription (STAT) signalling. These findings suggested to researchers that classical HL has a genetically driven and, ideally, targetable dependence on the PD-1 pathway for survival, Dr. Armand explained.

To test this idea, he and colleagues studied 23 patients with relapsed or refractory HL that had been heavily pre-treated who were part of an independent expansion cohort of a study of nivolumab in hematologic malignancies. Of these patients, 78% were enrolled after a relapse following autologous stem cell transplantation, and 22% after treatment with brentuximab vedotin had failed.

The patients received nivolumab 3 mg/kg every 2 weeks until they had either a complete response, tumor progression, or excessive side effects. In all, 20 of the 23 patients (87%) had an objective response to the single-agent therapy, including 4 (17%) complete responses and 16 (70%) partial responses. The remaining three patients (13%) had stable disease.

The longest time on study at the data cutoff point was 72 weeks. Among all responders, 60% had a response by 8 weeks of therapy, 48% are ongoing, and 43% of patients are still on treatment.

Drug-related adverse events were reported in 18 patients, most commonly rash and decreased platelet count. Five patients had grade 3 events. There were no drug-related grade 4 events or deaths.

In an editorial accompanying the study, which was also published online in The New England Journal of Medicine, Dr. Mario Sznoll and Dr. Dan L. Longo from the Yale University School of Medicine in New Haven, Connecticut write that “with recent data showing impressive clinical activity of PD-1 or PD-L1 antagonists in subgroups of patients with a variety of different cancers, the critical and foundational role of immune interventions in cancer treatment is no longer deniable,” (NEJM, Dec. 6, 2014 [DOI: 10.1056/NEJMoa1411087]).

Pembrolizumab trial

Dr. Craig H. Moskowitz from Memorial Sloan-Kettering Cancer Center in New York City discussed results of the second study, dubbed KEYNOTE-013 (A Phase Ib Multi-Cohort Trial of MK-3475 in Subjects With Hematologic Malignancies).

In this study, patients with HL who were not transplant eligible or for whom transplant had failed and who either had a relapse or were refractory to therapy with brentuximab vedotin received 19 mg/kg IV infusion of pembrolizumab every 2 weeks until complete response, partial response/stable disease, or disease progression.

Of the 31 patients enrolled, 29 were available for the analysis. As of the data cutoff in November 2014, 6 patients (21%) had achieved a complete remission, and 13 (45%) had a partial response, for an overall response rate of 66%. The median time to response was 12 weeks, and as of the data cutoff 17 of 19 patients had ongoing responses. The median response duration has not yet been reached. An additional 6 patients (21%) had stable disease, leading to an overall clinical benefit rate (responses plus stable disease) of 86%.

The patients generally tolerated the drug well. There were 4 treatment-related adverse events in 3 patients, including axillary pain, hypoxia, joint swelling, and pneumonitis. There were no grade 4 treatment-related events or deaths.

Of the tumor samples evaluable, all expressed PD-L1, supporting the rationale for PD-1 blockade in this population, Dr. Moskowitz said.

The results of both his and Dr. Armand’s study support the continued development of PD-1 inhibitors in various subsets of patients with classical Hodgkin’s lymphoma, he said.

SAN FRANCISCO– PD-1 checkpoint inhibitors, which have shown remarkable efficacy against advanced malignant melanoma, appear to hold similar promise in the treatment of relapsed or refractory Hodgkin’s lymphoma, results from two early studies suggest.

In a phase I study, the PD-1 blocking antibody nivolumab produced an 87% response rate in 23 heavily pre-treated patients with relapsed Hodgkin’s lymphoma (HL). In a separate phase Ib study, pembrolizumab, which blocks the PD-1 and PD-2 ligands, produced a 66% overall response rate, 21% complete remission rate, and 86% clinical benefit rate among 29 patients with HL for whom therapy with brentuximab vedotin (Adcetris) had failed.

The studies were presented at a media briefing prior to the presentation of data in oral sessions at the annual meeting of the American Society of Hematology.

“Classical Hodgkin lymphoma appears to be a tumor with genetically determined vulnerability to PD-1 blockade. We hope that PD-1 blockade in the future can become an important part of the treatment of patients with Hodgkin lymphoma,” said Dr. Phillipe Armand from the Dana-Farber Cancer Institute in Boston, an investigator for the nivolumab study.

Neil Osterweil/Frontline Medical News

Evidence from preclinical studies suggests that the Reed-Sternberg malignant cells characteristic of HL may use the PD-1 (programmed death 1) pathway to evade detection by immune cells, as suggested by pathologic studies showing the cells surrounded by an extensive but ineffective infiltrate of inflammatory cells.

“We’ve wondered for a long time how Hodgkin lymphoma could attract such a brisk immune response and yet have this immune response fail to kill the tumor,” he said.

Genetic Achilles heel

Genetic analyses had shown that HL frequently has a mutation that results in amplification of a region on chromosome 9 (9p24.1) which leads to increased expression of PD-1 ligands 1 and 2, and leads to a downregulation or weakening of the immune response. The mutation appears to work through the Janus kinase (JAK)-signal transducer and activator transcription (STAT) signalling. These findings suggested to researchers that classical HL has a genetically driven and, ideally, targetable dependence on the PD-1 pathway for survival, Dr. Armand explained.

To test this idea, he and colleagues studied 23 patients with relapsed or refractory HL that had been heavily pre-treated who were part of an independent expansion cohort of a study of nivolumab in hematologic malignancies. Of these patients, 78% were enrolled after a relapse following autologous stem cell transplantation, and 22% after treatment with brentuximab vedotin had failed.

The patients received nivolumab 3 mg/kg every 2 weeks until they had either a complete response, tumor progression, or excessive side effects. In all, 20 of the 23 patients (87%) had an objective response to the single-agent therapy, including 4 (17%) complete responses and 16 (70%) partial responses. The remaining three patients (13%) had stable disease.

The longest time on study at the data cutoff point was 72 weeks. Among all responders, 60% had a response by 8 weeks of therapy, 48% are ongoing, and 43% of patients are still on treatment.

Drug-related adverse events were reported in 18 patients, most commonly rash and decreased platelet count. Five patients had grade 3 events. There were no drug-related grade 4 events or deaths.

In an editorial accompanying the study, which was also published online in The New England Journal of Medicine, Dr. Mario Sznoll and Dr. Dan L. Longo from the Yale University School of Medicine in New Haven, Connecticut write that “with recent data showing impressive clinical activity of PD-1 or PD-L1 antagonists in subgroups of patients with a variety of different cancers, the critical and foundational role of immune interventions in cancer treatment is no longer deniable,” (NEJM, Dec. 6, 2014 [DOI: 10.1056/NEJMoa1411087]).

Pembrolizumab trial

Dr. Craig H. Moskowitz from Memorial Sloan-Kettering Cancer Center in New York City discussed results of the second study, dubbed KEYNOTE-013 (A Phase Ib Multi-Cohort Trial of MK-3475 in Subjects With Hematologic Malignancies).

In this study, patients with HL who were not transplant eligible or for whom transplant had failed and who either had a relapse or were refractory to therapy with brentuximab vedotin received 19 mg/kg IV infusion of pembrolizumab every 2 weeks until complete response, partial response/stable disease, or disease progression.

Of the 31 patients enrolled, 29 were available for the analysis. As of the data cutoff in November 2014, 6 patients (21%) had achieved a complete remission, and 13 (45%) had a partial response, for an overall response rate of 66%. The median time to response was 12 weeks, and as of the data cutoff 17 of 19 patients had ongoing responses. The median response duration has not yet been reached. An additional 6 patients (21%) had stable disease, leading to an overall clinical benefit rate (responses plus stable disease) of 86%.

The patients generally tolerated the drug well. There were 4 treatment-related adverse events in 3 patients, including axillary pain, hypoxia, joint swelling, and pneumonitis. There were no grade 4 treatment-related events or deaths.

Of the tumor samples evaluable, all expressed PD-L1, supporting the rationale for PD-1 blockade in this population, Dr. Moskowitz said.

The results of both his and Dr. Armand’s study support the continued development of PD-1 inhibitors in various subsets of patients with classical Hodgkin’s lymphoma, he said.

Time to progression was inferior in patients with advanced-stage nodular lymphocyte-predominant Hodgkin’s lymphoma, compared with patients with classical Hodgkin’s lymphoma, in a study that compared outcomes between the two groups of Hodgkin’s lymphoma patients enrolled in the British Columbia Cancer Agency database.

Over 10 years, time to progression was 63% in the nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) group, vs. 73% in the classical Hodgkin’s lymphoma (CHL) group (P =.040), reported Dr. Katharine Xing of the Centre for Lymphoid Cancer at the BCCA and the University of British Columbia, Vancouver, and her associates.

Transformation to an aggressive non–Hodgkin’s lymphoma (NHL) over 15 years occurred in 24% of those with NLPHL, but in none of those with CHL (P = .00018), and the median time to transformation among those with NLPHL was 5.45 years (Blood 2014;123:3567-73).

The study compared 42 patients with advanced-stage NLPHL to 84 controls with advanced CHL, matched for age, sex, decade of diagnosis, stage, and chemotherapy type; all had been diagnosed between 1970 and 2011. Their mean age was 37 years, about two-thirds were men, most in both groups had stage III disease, and they were followed up for a median of about 11 years. Treatments included standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and most received standard ABVD or ABVD-equivalent chemotherapy. The study was conducted to "highlight the distinct natural history of this rare HL subtype," which accounts for 5% of HL cases, the authors noted.

Over 10 years, "HL freedom from treatment failure," which reflects only relapses from HL, was 75% among those with NLPHL and 73% among those with CHL. Overall survival was also similar between the two groups (83.5% among those with NLPHL and 81% among those with CHL at 10 years).

Among their other findings was a significantly higher incidence of transformation over 10 years among those who had splenic involvement at the time of NLPHL diagnosis, compared with those who did not have splenic involvement (29% vs. 7.8%). When they looked at only those NLPHL patients who had received ABVD-like treatment, the incidence of transformation over 10 years was 34% among those with splenic involvement at diagnosis, vs. 9% among those who did not have splenic involvement (P = .014).

Since NLPHL is rare, information on the optimal treatment is limited, particularly for those with advanced disease, the authors pointed out. The analysis "highlights the distinct disease behavior of NLPHL, compared with CHL, and the need for repeat biopsy at relapse as well as long-term surveillance," the authors concluded. "Given the strong expression of CD20" on the lymphocyte predominant cells that distinguishes NLPHL from CHL, the results also provide "a rationale for further evaluation" of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with rituximab, they added.

emechcatie@frontlinemedcom.com

Time to progression was inferior in patients with advanced-stage nodular lymphocyte-predominant Hodgkin’s lymphoma, compared with patients with classical Hodgkin’s lymphoma, in a study that compared outcomes between the two groups of Hodgkin’s lymphoma patients enrolled in the British Columbia Cancer Agency database.

Over 10 years, time to progression was 63% in the nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) group, vs. 73% in the classical Hodgkin’s lymphoma (CHL) group (P =.040), reported Dr. Katharine Xing of the Centre for Lymphoid Cancer at the BCCA and the University of British Columbia, Vancouver, and her associates.

Transformation to an aggressive non–Hodgkin’s lymphoma (NHL) over 15 years occurred in 24% of those with NLPHL, but in none of those with CHL (P = .00018), and the median time to transformation among those with NLPHL was 5.45 years (Blood 2014;123:3567-73).

The study compared 42 patients with advanced-stage NLPHL to 84 controls with advanced CHL, matched for age, sex, decade of diagnosis, stage, and chemotherapy type; all had been diagnosed between 1970 and 2011. Their mean age was 37 years, about two-thirds were men, most in both groups had stage III disease, and they were followed up for a median of about 11 years. Treatments included standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and most received standard ABVD or ABVD-equivalent chemotherapy. The study was conducted to "highlight the distinct natural history of this rare HL subtype," which accounts for 5% of HL cases, the authors noted.

Over 10 years, "HL freedom from treatment failure," which reflects only relapses from HL, was 75% among those with NLPHL and 73% among those with CHL. Overall survival was also similar between the two groups (83.5% among those with NLPHL and 81% among those with CHL at 10 years).

Among their other findings was a significantly higher incidence of transformation over 10 years among those who had splenic involvement at the time of NLPHL diagnosis, compared with those who did not have splenic involvement (29% vs. 7.8%). When they looked at only those NLPHL patients who had received ABVD-like treatment, the incidence of transformation over 10 years was 34% among those with splenic involvement at diagnosis, vs. 9% among those who did not have splenic involvement (P = .014).

Since NLPHL is rare, information on the optimal treatment is limited, particularly for those with advanced disease, the authors pointed out. The analysis "highlights the distinct disease behavior of NLPHL, compared with CHL, and the need for repeat biopsy at relapse as well as long-term surveillance," the authors concluded. "Given the strong expression of CD20" on the lymphocyte predominant cells that distinguishes NLPHL from CHL, the results also provide "a rationale for further evaluation" of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with rituximab, they added.

emechcatie@frontlinemedcom.com

Time to progression was inferior in patients with advanced-stage nodular lymphocyte-predominant Hodgkin’s lymphoma, compared with patients with classical Hodgkin’s lymphoma, in a study that compared outcomes between the two groups of Hodgkin’s lymphoma patients enrolled in the British Columbia Cancer Agency database.

Over 10 years, time to progression was 63% in the nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) group, vs. 73% in the classical Hodgkin’s lymphoma (CHL) group (P =.040), reported Dr. Katharine Xing of the Centre for Lymphoid Cancer at the BCCA and the University of British Columbia, Vancouver, and her associates.

Transformation to an aggressive non–Hodgkin’s lymphoma (NHL) over 15 years occurred in 24% of those with NLPHL, but in none of those with CHL (P = .00018), and the median time to transformation among those with NLPHL was 5.45 years (Blood 2014;123:3567-73).

The study compared 42 patients with advanced-stage NLPHL to 84 controls with advanced CHL, matched for age, sex, decade of diagnosis, stage, and chemotherapy type; all had been diagnosed between 1970 and 2011. Their mean age was 37 years, about two-thirds were men, most in both groups had stage III disease, and they were followed up for a median of about 11 years. Treatments included standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and most received standard ABVD or ABVD-equivalent chemotherapy. The study was conducted to "highlight the distinct natural history of this rare HL subtype," which accounts for 5% of HL cases, the authors noted.

Over 10 years, "HL freedom from treatment failure," which reflects only relapses from HL, was 75% among those with NLPHL and 73% among those with CHL. Overall survival was also similar between the two groups (83.5% among those with NLPHL and 81% among those with CHL at 10 years).

Among their other findings was a significantly higher incidence of transformation over 10 years among those who had splenic involvement at the time of NLPHL diagnosis, compared with those who did not have splenic involvement (29% vs. 7.8%). When they looked at only those NLPHL patients who had received ABVD-like treatment, the incidence of transformation over 10 years was 34% among those with splenic involvement at diagnosis, vs. 9% among those who did not have splenic involvement (P = .014).

Since NLPHL is rare, information on the optimal treatment is limited, particularly for those with advanced disease, the authors pointed out. The analysis "highlights the distinct disease behavior of NLPHL, compared with CHL, and the need for repeat biopsy at relapse as well as long-term surveillance," the authors concluded. "Given the strong expression of CD20" on the lymphocyte predominant cells that distinguishes NLPHL from CHL, the results also provide "a rationale for further evaluation" of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with rituximab, they added.

emechcatie@frontlinemedcom.com

Diffuse large B-cell lymphoma of the lung is a rare entity, and although the prognosis is favorable, its biological features, clinical presentation, prognostic markers, and treatment have not been well defined.^1,2 It is the second most common primary pulmonary lymphoma after mucosa-associated lymphoid tissue. PPL itself is very rare; it represents 3%-4% of extranodal non-Hodgkin lymphoma, less than 1% of NHL, and 0.5%-1.0% of primary pulmonary malignancies.^2,3 A review of the literature indicates a lack of data on pulmonary DLBCL. The objective of this case report is to highlight areas in which further research may be pursued to better understand this disease.
 

Click on the PDF icon at the top of this introduction to read the full article.

Diffuse large B-cell lymphoma of the lung is a rare entity, and although the prognosis is favorable, its biological features, clinical presentation, prognostic markers, and treatment have not been well defined.^1,2 It is the second most common primary pulmonary lymphoma after mucosa-associated lymphoid tissue. PPL itself is very rare; it represents 3%-4% of extranodal non-Hodgkin lymphoma, less than 1% of NHL, and 0.5%-1.0% of primary pulmonary malignancies.^2,3 A review of the literature indicates a lack of data on pulmonary DLBCL. The objective of this case report is to highlight areas in which further research may be pursued to better understand this disease.
 

Click on the PDF icon at the top of this introduction to read the full article.

Diffuse large B-cell lymphoma of the lung is a rare entity, and although the prognosis is favorable, its biological features, clinical presentation, prognostic markers, and treatment have not been well defined.^1,2 It is the second most common primary pulmonary lymphoma after mucosa-associated lymphoid tissue. PPL itself is very rare; it represents 3%-4% of extranodal non-Hodgkin lymphoma, less than 1% of NHL, and 0.5%-1.0% of primary pulmonary malignancies.^2,3 A review of the literature indicates a lack of data on pulmonary DLBCL. The objective of this case report is to highlight areas in which further research may be pursued to better understand this disease.
 

Click on the PDF icon at the top of this introduction to read the full article.

NEW ORLEANS – When indolent B-cell non-Hodgkin lymphoma becomes refractory to rituximab and alkylating agents, few therapeutic options remain. But the PI3kd inhibitor idelalisib may someday offer a new treatment choice. Dr. Ajay Gopal discusses the promising findings from a phase II trial of idelalisib, including a 57% response rate.

NEW ORLEANS – When indolent B-cell non-Hodgkin lymphoma becomes refractory to rituximab and alkylating agents, few therapeutic options remain. But the PI3kd inhibitor idelalisib may someday offer a new treatment choice. Dr. Ajay Gopal discusses the promising findings from a phase II trial of idelalisib, including a 57% response rate.

NEW ORLEANS – When indolent B-cell non-Hodgkin lymphoma becomes refractory to rituximab and alkylating agents, few therapeutic options remain. But the PI3kd inhibitor idelalisib may someday offer a new treatment choice. Dr. Ajay Gopal discusses the promising findings from a phase II trial of idelalisib, including a 57% response rate.

CHICAGO – Routine surveillance imaging does not improve clinical outcomes in patients with classic Hodgkin disease who are in first complete remission and it sharply increases costs, researchers reported at the annual meeting of the American Society of Clinical Oncology.

The team, led by Dr. Sai Ravi Pingali, retrospectively reviewed the charts of 241 adult patients who achieved a complete remission after first-line therapy.

In 68%, the treating physicians’ planned approach was routine surveillance imaging, which consisted of radiologic imaging with scans every few months, plus clinical exams and laboratory testing. In the other 32%, the planned approach was clinical surveillance, meaning that radiologic imaging was performed only if concerning signs or symptoms occurred.

The two groups had statistically indistinguishable overall survival, and in both groups, all patients experiencing relapse successfully achieved a second complete remission with salvage therapy.

In the routinely imaged group, scanning increased costs by nearly $20,000 per patient and by almost $600,000 per each relapse detected. In addition, patients were exposed to the associated radiation.

"We were unable to detect an overall survival benefit associated with routine surveillance imaging, although I have to acknowledge that our study was limited in power given the small number of deaths and relapses," commented Dr. Pingali, an oncologist with the Medical College of Wisconsin Affiliated Hospitals in Milwaukee.

"Relapses in both ... groups were effectively salvaged with autologous stem cell transplantation, arguing against a critical advantage of detection of asymptomatic relapse. Also, we need to keep in mind that the costs associated with routine surveillance imaging are significant, and it is also associated with potential risks, both in terms of radiation exposure and unnecessary work-up," he added.

"We do not feel that potential risks and costs without overall survival benefit or any other clinical benefit justify the practice of routine surveillance imaging in classical Hodgkin lymphoma patients who have achieved a complete remission after first-line therapy. We recommend that such patients be followed clinically," Dr. Pingali concluded.

Invited discussant Dr. Leo Gordon of Northwestern University in Chicago, agreed that accumulating data argue against routine imaging for surveillance in this context and noted that insurers will likely not continue to cover scans having no proven benefit. The data should prompt a revision of guidelines and reeducation of clinicians and patients, he said.

"For translational researchers and investigators and academics, I think we need to convince journal reviewers that a manuscript is acceptable if scans are not so frequent. And for industry trials, I think we need to discuss with the Food and Drug Administration the endpoint of progression-free survival and that those endpoints may not only be driven by scans but by more mundane parameters," he said—namely, the history and physical examination.

But session comoderator Dr. Gilles A. Salles of Hospices Civils de Lyon, Université Claude Bernard, France, expressed reservations, noting that the study did not provide information on how patients were allocated to groups and the time frame of relapse.

"It may be different whether relapses occur early, in the first year, or they occur later, and that may have some implications for the surveillance," he said. "I understand that you and many others jumped over the idea that we should immediately stop. A few people may think that we need more solid data, despite the provocative and quality data that were presented, to really make this jump in clinical practice. That’s my personal opinion."

Dr. Pingali and his team retrospectively reviewed the charts of adult patients who received a new diagnosis of classical Hodgkin lymphoma between 2000 and 2010 at three institutions, achieved complete remission after first-line therapy and had at least 2 years of follow-up.

The routine surveillance imaging and clinical surveillance groups had similar demographic and disease characteristics, Dr. Pingali reported. The former were significantly more likely to have received ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) and less likely to have received the Stanford V regimen as first-line therapy, and they were significantly less likely to have received radiation therapy.

With a median duration of follow-up of about 4 years, the groups did not differ significantly with respect to overall survival. "When we look at the 5-year time point, when typically the surveillance CT scans are discontinued, the curves are pretty much superimposable," he pointed out.

There were five deaths in the routine surveillance imaging group, one of which was from relapsed disease; the other deaths were from cancer, heart failure, hip fracture, and myelodysplastic syndrome. There were four deaths in the clinical surveillance group: two were from non-Hodgkin lymphoma and two from unknown causes while the patient was in confirmed remission.

All of the six patients in the routinely imaged group and all of the five patients in the clinically followed group experiencing a relapse achieved another complete remission with second-line therapy.

The mean number of scans received was 1.14 in the clinical surveillance group – usually the scan performed after first-line treatment to confirm remission, according to Dr. Pingali – and 4.25 in the routine surveillance imaging group. The ratio of scans to detected relapses was 18 vs. 124.

The extra charges incurred from scans using the routine surveillance imaging approach were $18,896/patient and $593,698/relapse.

"It is important to note that this does not include additional costs from the work-up of the false-positive scans and also the wages lost," he noted.

Dr. Pingali disclosed no relevant conflicts of interest. Dr. Gordon disclosed that he receives honoraria from Genentech and research funding from Millennium and Pharmacyclics. Dr. Salles disclosed serving as an advisor or consultant for Calistoga Pharmaceuticals, Celgene; Genentech, Janssen Pharmaceutica, and Roche. He has served as a speaker or a member of a speakers bureau and has received grants for clinical research from Celgene and Roche.

CHICAGO – Routine surveillance imaging does not improve clinical outcomes in patients with classic Hodgkin disease who are in first complete remission and it sharply increases costs, researchers reported at the annual meeting of the American Society of Clinical Oncology.

The team, led by Dr. Sai Ravi Pingali, retrospectively reviewed the charts of 241 adult patients who achieved a complete remission after first-line therapy.

In 68%, the treating physicians’ planned approach was routine surveillance imaging, which consisted of radiologic imaging with scans every few months, plus clinical exams and laboratory testing. In the other 32%, the planned approach was clinical surveillance, meaning that radiologic imaging was performed only if concerning signs or symptoms occurred.

The two groups had statistically indistinguishable overall survival, and in both groups, all patients experiencing relapse successfully achieved a second complete remission with salvage therapy.

In the routinely imaged group, scanning increased costs by nearly $20,000 per patient and by almost $600,000 per each relapse detected. In addition, patients were exposed to the associated radiation.

"We were unable to detect an overall survival benefit associated with routine surveillance imaging, although I have to acknowledge that our study was limited in power given the small number of deaths and relapses," commented Dr. Pingali, an oncologist with the Medical College of Wisconsin Affiliated Hospitals in Milwaukee.

"Relapses in both ... groups were effectively salvaged with autologous stem cell transplantation, arguing against a critical advantage of detection of asymptomatic relapse. Also, we need to keep in mind that the costs associated with routine surveillance imaging are significant, and it is also associated with potential risks, both in terms of radiation exposure and unnecessary work-up," he added.

"We do not feel that potential risks and costs without overall survival benefit or any other clinical benefit justify the practice of routine surveillance imaging in classical Hodgkin lymphoma patients who have achieved a complete remission after first-line therapy. We recommend that such patients be followed clinically," Dr. Pingali concluded.

Invited discussant Dr. Leo Gordon of Northwestern University in Chicago, agreed that accumulating data argue against routine imaging for surveillance in this context and noted that insurers will likely not continue to cover scans having no proven benefit. The data should prompt a revision of guidelines and reeducation of clinicians and patients, he said.

"For translational researchers and investigators and academics, I think we need to convince journal reviewers that a manuscript is acceptable if scans are not so frequent. And for industry trials, I think we need to discuss with the Food and Drug Administration the endpoint of progression-free survival and that those endpoints may not only be driven by scans but by more mundane parameters," he said—namely, the history and physical examination.

But session comoderator Dr. Gilles A. Salles of Hospices Civils de Lyon, Université Claude Bernard, France, expressed reservations, noting that the study did not provide information on how patients were allocated to groups and the time frame of relapse.

"It may be different whether relapses occur early, in the first year, or they occur later, and that may have some implications for the surveillance," he said. "I understand that you and many others jumped over the idea that we should immediately stop. A few people may think that we need more solid data, despite the provocative and quality data that were presented, to really make this jump in clinical practice. That’s my personal opinion."

Dr. Pingali and his team retrospectively reviewed the charts of adult patients who received a new diagnosis of classical Hodgkin lymphoma between 2000 and 2010 at three institutions, achieved complete remission after first-line therapy and had at least 2 years of follow-up.

The routine surveillance imaging and clinical surveillance groups had similar demographic and disease characteristics, Dr. Pingali reported. The former were significantly more likely to have received ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) and less likely to have received the Stanford V regimen as first-line therapy, and they were significantly less likely to have received radiation therapy.

With a median duration of follow-up of about 4 years, the groups did not differ significantly with respect to overall survival. "When we look at the 5-year time point, when typically the surveillance CT scans are discontinued, the curves are pretty much superimposable," he pointed out.

There were five deaths in the routine surveillance imaging group, one of which was from relapsed disease; the other deaths were from cancer, heart failure, hip fracture, and myelodysplastic syndrome. There were four deaths in the clinical surveillance group: two were from non-Hodgkin lymphoma and two from unknown causes while the patient was in confirmed remission.

All of the six patients in the routinely imaged group and all of the five patients in the clinically followed group experiencing a relapse achieved another complete remission with second-line therapy.

The mean number of scans received was 1.14 in the clinical surveillance group – usually the scan performed after first-line treatment to confirm remission, according to Dr. Pingali – and 4.25 in the routine surveillance imaging group. The ratio of scans to detected relapses was 18 vs. 124.

The extra charges incurred from scans using the routine surveillance imaging approach were $18,896/patient and $593,698/relapse.

"It is important to note that this does not include additional costs from the work-up of the false-positive scans and also the wages lost," he noted.

Dr. Pingali disclosed no relevant conflicts of interest. Dr. Gordon disclosed that he receives honoraria from Genentech and research funding from Millennium and Pharmacyclics. Dr. Salles disclosed serving as an advisor or consultant for Calistoga Pharmaceuticals, Celgene; Genentech, Janssen Pharmaceutica, and Roche. He has served as a speaker or a member of a speakers bureau and has received grants for clinical research from Celgene and Roche.

CHICAGO – Routine surveillance imaging does not improve clinical outcomes in patients with classic Hodgkin disease who are in first complete remission and it sharply increases costs, researchers reported at the annual meeting of the American Society of Clinical Oncology.

The team, led by Dr. Sai Ravi Pingali, retrospectively reviewed the charts of 241 adult patients who achieved a complete remission after first-line therapy.

In 68%, the treating physicians’ planned approach was routine surveillance imaging, which consisted of radiologic imaging with scans every few months, plus clinical exams and laboratory testing. In the other 32%, the planned approach was clinical surveillance, meaning that radiologic imaging was performed only if concerning signs or symptoms occurred.

The two groups had statistically indistinguishable overall survival, and in both groups, all patients experiencing relapse successfully achieved a second complete remission with salvage therapy.

In the routinely imaged group, scanning increased costs by nearly $20,000 per patient and by almost $600,000 per each relapse detected. In addition, patients were exposed to the associated radiation.

"We were unable to detect an overall survival benefit associated with routine surveillance imaging, although I have to acknowledge that our study was limited in power given the small number of deaths and relapses," commented Dr. Pingali, an oncologist with the Medical College of Wisconsin Affiliated Hospitals in Milwaukee.

"Relapses in both ... groups were effectively salvaged with autologous stem cell transplantation, arguing against a critical advantage of detection of asymptomatic relapse. Also, we need to keep in mind that the costs associated with routine surveillance imaging are significant, and it is also associated with potential risks, both in terms of radiation exposure and unnecessary work-up," he added.

"We do not feel that potential risks and costs without overall survival benefit or any other clinical benefit justify the practice of routine surveillance imaging in classical Hodgkin lymphoma patients who have achieved a complete remission after first-line therapy. We recommend that such patients be followed clinically," Dr. Pingali concluded.

Invited discussant Dr. Leo Gordon of Northwestern University in Chicago, agreed that accumulating data argue against routine imaging for surveillance in this context and noted that insurers will likely not continue to cover scans having no proven benefit. The data should prompt a revision of guidelines and reeducation of clinicians and patients, he said.

"For translational researchers and investigators and academics, I think we need to convince journal reviewers that a manuscript is acceptable if scans are not so frequent. And for industry trials, I think we need to discuss with the Food and Drug Administration the endpoint of progression-free survival and that those endpoints may not only be driven by scans but by more mundane parameters," he said—namely, the history and physical examination.

But session comoderator Dr. Gilles A. Salles of Hospices Civils de Lyon, Université Claude Bernard, France, expressed reservations, noting that the study did not provide information on how patients were allocated to groups and the time frame of relapse.

"It may be different whether relapses occur early, in the first year, or they occur later, and that may have some implications for the surveillance," he said. "I understand that you and many others jumped over the idea that we should immediately stop. A few people may think that we need more solid data, despite the provocative and quality data that were presented, to really make this jump in clinical practice. That’s my personal opinion."

Dr. Pingali and his team retrospectively reviewed the charts of adult patients who received a new diagnosis of classical Hodgkin lymphoma between 2000 and 2010 at three institutions, achieved complete remission after first-line therapy and had at least 2 years of follow-up.

The routine surveillance imaging and clinical surveillance groups had similar demographic and disease characteristics, Dr. Pingali reported. The former were significantly more likely to have received ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) and less likely to have received the Stanford V regimen as first-line therapy, and they were significantly less likely to have received radiation therapy.

With a median duration of follow-up of about 4 years, the groups did not differ significantly with respect to overall survival. "When we look at the 5-year time point, when typically the surveillance CT scans are discontinued, the curves are pretty much superimposable," he pointed out.

There were five deaths in the routine surveillance imaging group, one of which was from relapsed disease; the other deaths were from cancer, heart failure, hip fracture, and myelodysplastic syndrome. There were four deaths in the clinical surveillance group: two were from non-Hodgkin lymphoma and two from unknown causes while the patient was in confirmed remission.

All of the six patients in the routinely imaged group and all of the five patients in the clinically followed group experiencing a relapse achieved another complete remission with second-line therapy.

The mean number of scans received was 1.14 in the clinical surveillance group – usually the scan performed after first-line treatment to confirm remission, according to Dr. Pingali – and 4.25 in the routine surveillance imaging group. The ratio of scans to detected relapses was 18 vs. 124.

The extra charges incurred from scans using the routine surveillance imaging approach were $18,896/patient and $593,698/relapse.

"It is important to note that this does not include additional costs from the work-up of the false-positive scans and also the wages lost," he noted.

Dr. Pingali disclosed no relevant conflicts of interest. Dr. Gordon disclosed that he receives honoraria from Genentech and research funding from Millennium and Pharmacyclics. Dr. Salles disclosed serving as an advisor or consultant for Calistoga Pharmaceuticals, Celgene; Genentech, Janssen Pharmaceutica, and Roche. He has served as a speaker or a member of a speakers bureau and has received grants for clinical research from Celgene and Roche.