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JULIET: CAR T cells keep trucking against DLBCL
SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.
After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.
“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.
The updated study results were published simultaneously online in the New England Journal of Medicine.
JULIET then
In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.
Interim results of the study were previously reported at the European Hematology Association Congress in 2017.
At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.
JULIET now
In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.
The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.
Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.
The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.
Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.
There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.
“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.
The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.
SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.
After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.
“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.
The updated study results were published simultaneously online in the New England Journal of Medicine.
JULIET then
In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.
Interim results of the study were previously reported at the European Hematology Association Congress in 2017.
At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.
JULIET now
In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.
The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.
Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.
The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.
Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.
There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.
“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.
The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.
SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.
After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.
“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.
The updated study results were published simultaneously online in the New England Journal of Medicine.
JULIET then
In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.
Interim results of the study were previously reported at the European Hematology Association Congress in 2017.
At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.
JULIET now
In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.
The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.
Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.
The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.
Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.
There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.
“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.
The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.
SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
REPORTING FROM ASH 2018
Key clinical point: Chimeric antigen receptor T-cell therapy produced durable responses in patients with heavily pretreated diffuse large B-cell lymphoma.
Major finding: The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses.
Study details: A single-arm, open-label study of tisagenlecleucel in adults with relapsed or refractory diffuse large B-cell lymphoma.
Disclosures: The JULIET trial is supported by Novartis. Dr. Maziarz reported personal fees from Incyte, Kite Therapeutics, and Athersys.
Source: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
FLYER: Four cycles of R-CHOP as good as six in low-risk DLBCL
SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in the FLYER trial reported.
Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.
“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.
For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.
The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (Lancet Oncol. 2006 May;7[5]379-91). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.
At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.
“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.
Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.
R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.
Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.
Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.
As noted before, the total number of nonhematologic adverse events was reduced by about one-third.
“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented David Steensma, MD, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.
Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.
“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.
The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.
SOURCE: Poeschel V et al. ASH 2018, Abstract 781.
SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in the FLYER trial reported.
Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.
“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.
For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.
The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (Lancet Oncol. 2006 May;7[5]379-91). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.
At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.
“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.
Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.
R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.
Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.
Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.
As noted before, the total number of nonhematologic adverse events was reduced by about one-third.
“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented David Steensma, MD, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.
Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.
“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.
The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.
SOURCE: Poeschel V et al. ASH 2018, Abstract 781.
SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in the FLYER trial reported.
Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.
“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.
For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.
The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (Lancet Oncol. 2006 May;7[5]379-91). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.
At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.
“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.
Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.
R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.
Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.
Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.
As noted before, the total number of nonhematologic adverse events was reduced by about one-third.
“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented David Steensma, MD, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.
Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.
“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.
The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.
SOURCE: Poeschel V et al. ASH 2018, Abstract 781.
REPORTING FROM ASH 2018
Key clinical point: Four cycles of R-CHOP was noninferior to six cycles in younger patients with favorable-prognosis diffuse large B-cell lymphoma.
Major finding: R-CHOP 4 was noninferior to R-CHOP 6 for the primary progression-free survival endpoint.
Study details: A randomized trial in 588 patients with favorable-prognosis diffuse large B-cell lymphoma.
Disclosures: The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.
Source: Poeschel V et al. ASH 2018, Abstract 781.
FLYER: R-CHOP 4 safer, as effective for low-risk DLBCL patients under 60
SAN DIEGO – Patients aged younger than 60 years with favorable-prognosis diffuse large B-cell lymphoma who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) had progression-free, event-free, and overall survival rates comparable with those of patients assigned to six cycles, investigators in the FLYER trial reported.
The four-cycle regimen was associated with a marked reduction in adverse events, with an overall drop in nonhematologic malignancies of approximately one-third compared with the six-cycle regimen.
For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care.
In this video interview at the annual meeting of the American Society of Hematology, Viola Poeschel, MD, of Saarland University in Homburg, Germany, describes the patient population who may benefit from shorter duration therapy.
SAN DIEGO – Patients aged younger than 60 years with favorable-prognosis diffuse large B-cell lymphoma who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) had progression-free, event-free, and overall survival rates comparable with those of patients assigned to six cycles, investigators in the FLYER trial reported.
The four-cycle regimen was associated with a marked reduction in adverse events, with an overall drop in nonhematologic malignancies of approximately one-third compared with the six-cycle regimen.
For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care.
In this video interview at the annual meeting of the American Society of Hematology, Viola Poeschel, MD, of Saarland University in Homburg, Germany, describes the patient population who may benefit from shorter duration therapy.
SAN DIEGO – Patients aged younger than 60 years with favorable-prognosis diffuse large B-cell lymphoma who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) had progression-free, event-free, and overall survival rates comparable with those of patients assigned to six cycles, investigators in the FLYER trial reported.
The four-cycle regimen was associated with a marked reduction in adverse events, with an overall drop in nonhematologic malignancies of approximately one-third compared with the six-cycle regimen.
For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care.
In this video interview at the annual meeting of the American Society of Hematology, Viola Poeschel, MD, of Saarland University in Homburg, Germany, describes the patient population who may benefit from shorter duration therapy.
REPORTING FROM ASH 2018
CNS lymphoma guidelines stress patient fitness, not age, in choosing treatment
for the diagnosis and management of primary central nervous system diffuse large B‐cell lymphoma.
PCNSL, implicated in some 3% of all brain tumors, is complex to diagnose and treat. People with suspected PCNSL must receive quick and coordinated attention from a multidisciplinary team of neurologists, hematologist-oncologists, and ocular specialists, according to the guidelines, published in the British Journal of Haematology.
Christopher P. Fox, MD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues, stress the importance of early multidisciplinary attention, aggressive induction treatment, helping patients into trials, universal screening for eye involvement, attaining histological diagnoses in addition to imaging findings, and avoidance or discontinuation of any corticosteroids before biopsy, as even a short course of steroids can impede diagnosis.
The guidelines incorporate findings from studies published since the society’s last comprehensive PCNSL guideline was issued more than a decade ago.
Dr. Fox and his colleagues say definitive treatment for PCNSL – induction of remission followed by consolidation – should start within 2 weeks of diagnosis and that a treatment regimen should be chosen according to a patient’s physiological fitness, not age. The fittest patients, who have better organ function and fewer comorbidities, should be eligible for intensive combination immunochemotherapy incorporating high-dose methotrexate (optimally four cycles of HD-MTX, cytarabine, thiotepa, and rituximab). Those deemed unfit for this regimen should be offered induction treatment with HD-MTX, rituximab and procarbazine, the guidelines’ authors say.
If patients cannot tolerate HD-MTX, oral chemotherapy and/or whole-brain radiotherapy may be offered. Response should be assessed with contrast-enhanced magnetic resonance imaging.
Consolidation therapy should be initiated after induction for all patients with nonprogressive disease, and high-dose thiotepa-based chemotherapy with autologous stem cell transplant is the recommended first-line option for consolidation. Response to consolidation, again measured with contrast-enhanced MRI, should be carried out at between 1 and 2 months after therapy is completed, and patients should be referred for neuropsychological testing to assess cognitive function.
Patients with relapsed or refractory disease should be approached with maximum urgency – the guidelines offer an algorithm for retreatment options – and offered clinical trial entry wherever possible.
The PCNSL guideline writing process was sponsored by the British Society for Haematology, and some coauthors, including the lead author, disclosed receiving fees from pharmaceutical manufacturers Adienne or F. Hoffman-La Roche.
SOURCE: Fox et al. Br J Haematol. 2018 Nov 23 doi: 10.1111/bjh.15661.
for the diagnosis and management of primary central nervous system diffuse large B‐cell lymphoma.
PCNSL, implicated in some 3% of all brain tumors, is complex to diagnose and treat. People with suspected PCNSL must receive quick and coordinated attention from a multidisciplinary team of neurologists, hematologist-oncologists, and ocular specialists, according to the guidelines, published in the British Journal of Haematology.
Christopher P. Fox, MD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues, stress the importance of early multidisciplinary attention, aggressive induction treatment, helping patients into trials, universal screening for eye involvement, attaining histological diagnoses in addition to imaging findings, and avoidance or discontinuation of any corticosteroids before biopsy, as even a short course of steroids can impede diagnosis.
The guidelines incorporate findings from studies published since the society’s last comprehensive PCNSL guideline was issued more than a decade ago.
Dr. Fox and his colleagues say definitive treatment for PCNSL – induction of remission followed by consolidation – should start within 2 weeks of diagnosis and that a treatment regimen should be chosen according to a patient’s physiological fitness, not age. The fittest patients, who have better organ function and fewer comorbidities, should be eligible for intensive combination immunochemotherapy incorporating high-dose methotrexate (optimally four cycles of HD-MTX, cytarabine, thiotepa, and rituximab). Those deemed unfit for this regimen should be offered induction treatment with HD-MTX, rituximab and procarbazine, the guidelines’ authors say.
If patients cannot tolerate HD-MTX, oral chemotherapy and/or whole-brain radiotherapy may be offered. Response should be assessed with contrast-enhanced magnetic resonance imaging.
Consolidation therapy should be initiated after induction for all patients with nonprogressive disease, and high-dose thiotepa-based chemotherapy with autologous stem cell transplant is the recommended first-line option for consolidation. Response to consolidation, again measured with contrast-enhanced MRI, should be carried out at between 1 and 2 months after therapy is completed, and patients should be referred for neuropsychological testing to assess cognitive function.
Patients with relapsed or refractory disease should be approached with maximum urgency – the guidelines offer an algorithm for retreatment options – and offered clinical trial entry wherever possible.
The PCNSL guideline writing process was sponsored by the British Society for Haematology, and some coauthors, including the lead author, disclosed receiving fees from pharmaceutical manufacturers Adienne or F. Hoffman-La Roche.
SOURCE: Fox et al. Br J Haematol. 2018 Nov 23 doi: 10.1111/bjh.15661.
for the diagnosis and management of primary central nervous system diffuse large B‐cell lymphoma.
PCNSL, implicated in some 3% of all brain tumors, is complex to diagnose and treat. People with suspected PCNSL must receive quick and coordinated attention from a multidisciplinary team of neurologists, hematologist-oncologists, and ocular specialists, according to the guidelines, published in the British Journal of Haematology.
Christopher P. Fox, MD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues, stress the importance of early multidisciplinary attention, aggressive induction treatment, helping patients into trials, universal screening for eye involvement, attaining histological diagnoses in addition to imaging findings, and avoidance or discontinuation of any corticosteroids before biopsy, as even a short course of steroids can impede diagnosis.
The guidelines incorporate findings from studies published since the society’s last comprehensive PCNSL guideline was issued more than a decade ago.
Dr. Fox and his colleagues say definitive treatment for PCNSL – induction of remission followed by consolidation – should start within 2 weeks of diagnosis and that a treatment regimen should be chosen according to a patient’s physiological fitness, not age. The fittest patients, who have better organ function and fewer comorbidities, should be eligible for intensive combination immunochemotherapy incorporating high-dose methotrexate (optimally four cycles of HD-MTX, cytarabine, thiotepa, and rituximab). Those deemed unfit for this regimen should be offered induction treatment with HD-MTX, rituximab and procarbazine, the guidelines’ authors say.
If patients cannot tolerate HD-MTX, oral chemotherapy and/or whole-brain radiotherapy may be offered. Response should be assessed with contrast-enhanced magnetic resonance imaging.
Consolidation therapy should be initiated after induction for all patients with nonprogressive disease, and high-dose thiotepa-based chemotherapy with autologous stem cell transplant is the recommended first-line option for consolidation. Response to consolidation, again measured with contrast-enhanced MRI, should be carried out at between 1 and 2 months after therapy is completed, and patients should be referred for neuropsychological testing to assess cognitive function.
Patients with relapsed or refractory disease should be approached with maximum urgency – the guidelines offer an algorithm for retreatment options – and offered clinical trial entry wherever possible.
The PCNSL guideline writing process was sponsored by the British Society for Haematology, and some coauthors, including the lead author, disclosed receiving fees from pharmaceutical manufacturers Adienne or F. Hoffman-La Roche.
SOURCE: Fox et al. Br J Haematol. 2018 Nov 23 doi: 10.1111/bjh.15661.
FROM THE BRITISH JOURNAL OF HAEMATOLOGY
FDA approves rituximab biosimilar for lymphoma
(NHL).
Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan (rituximab) and the first biosimilar approved in the United States to treat NHL.
Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy. Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL. Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.
Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy. Truxima also is approved as a single agent to treat nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.
The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”
Findings from a phase 3 trial suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma (Lancet Haematol. 2018 Nov;5[11]:e543-53).
(NHL).
Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan (rituximab) and the first biosimilar approved in the United States to treat NHL.
Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy. Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL. Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.
Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy. Truxima also is approved as a single agent to treat nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.
The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”
Findings from a phase 3 trial suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma (Lancet Haematol. 2018 Nov;5[11]:e543-53).
(NHL).
Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan (rituximab) and the first biosimilar approved in the United States to treat NHL.
Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy. Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL. Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.
Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy. Truxima also is approved as a single agent to treat nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.
The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”
Findings from a phase 3 trial suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma (Lancet Haematol. 2018 Nov;5[11]:e543-53).
Cortactin expression aids in CLL-MCL differential
The presence or absence in tumor cells of cortactin, a cytoskeleton-remodeling adapter protein, may be a marker to help pathologists distinguish between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), investigators suggest.
A study of cortactin expression in tumor samples from patients with B-cell CLL, MCL, and other hematologic malignancies showed that while cortactin was present in 14 of 17 CLL samples, it was not expressed on any of 16 MCL samples, reported Marco Pizzi, MD, PhD, from the University of Padova (Italy) and his colleagues.
“In particular, cortactin may contribute to the differential diagnosis between CLL and MCL, two neoplasms with similar histological features but very different clinical outcome. Further studies are needed to clarify the molecular mechanisms of deranged cortactin expression in MCL and CLL and to investigate any possible relationship between cortactin status and the biological features of these lymphomas,” they wrote in Human Pathology.
Overexpression of cortactin has been reported in several solid tumors, and increased expression of CTTN, the gene encoding for cortactin, has been associated with aggressive, poor prognosis disease, the investigators noted.
To characterize cortactin expression in lymphoid and hematopoietic cells and detect potential associations between cortactin and virulence of hematologic malignancies, the investigators performed immunohistochemical analysis on samples from 131 patients treated at their center. The samples included 17 cases of CLL, 16 of MCL, 25 of follicular lymphoma (FL), 30 of marginal zone lymphoma (MZL), 10 of hairy cell leukemia, three of splenic diffuse red pulp small B-cell lymphomas (SDRPBL), and 30 of diffuse large B-cell lymphoma (DLBCL).
They found that cortactin was expressed in 14 of the 17 CLL samples, all 10 of the HCL samples, and 22 of the 30 DLBCL samples. In contrast, there was no cortactin expression detected in any of either 16 MCL or three SDRPBL samples. The researchers found that 13 of 30 MZL samples had low-level staining. In FL, cortactin was expressed in 2 of the samples but in the remaining 23 cases the researchers found only scattered cortactin-positive lymphoid elements of non–B-cell lineage.
The investigators also found that cortactin expression in CLL correlated with other CLL-specific markers, and found that expression of two or more of the markers had 89.1% sensitivity, 100% specificity, a 100% positive predictive value, and 90.5% negative predictive value for a diagnosis of CLL.
In addition, they saw that the immunohistochemical results were similar to those for CTTN gene expression assessed by in silico analysis.
The investigators noted that CLL and MCL are challenging to differentiate from one another because of morphologic similarities and partially overlapping immunophenotypes.
“In this context, cortactin expression would strongly sustain a diagnosis of CLL over MCL, particularly in association with other CLL markers (i.e., LEF1 and CD200),” they wrote.
The study was internally supported. The authors declared no conflicts of interest.
SOURCE: Pizzi M et al. Hum Pathol. 2018 Nov 17. doi: 10.1016/j.humpath.2018.10.038.
The presence or absence in tumor cells of cortactin, a cytoskeleton-remodeling adapter protein, may be a marker to help pathologists distinguish between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), investigators suggest.
A study of cortactin expression in tumor samples from patients with B-cell CLL, MCL, and other hematologic malignancies showed that while cortactin was present in 14 of 17 CLL samples, it was not expressed on any of 16 MCL samples, reported Marco Pizzi, MD, PhD, from the University of Padova (Italy) and his colleagues.
“In particular, cortactin may contribute to the differential diagnosis between CLL and MCL, two neoplasms with similar histological features but very different clinical outcome. Further studies are needed to clarify the molecular mechanisms of deranged cortactin expression in MCL and CLL and to investigate any possible relationship between cortactin status and the biological features of these lymphomas,” they wrote in Human Pathology.
Overexpression of cortactin has been reported in several solid tumors, and increased expression of CTTN, the gene encoding for cortactin, has been associated with aggressive, poor prognosis disease, the investigators noted.
To characterize cortactin expression in lymphoid and hematopoietic cells and detect potential associations between cortactin and virulence of hematologic malignancies, the investigators performed immunohistochemical analysis on samples from 131 patients treated at their center. The samples included 17 cases of CLL, 16 of MCL, 25 of follicular lymphoma (FL), 30 of marginal zone lymphoma (MZL), 10 of hairy cell leukemia, three of splenic diffuse red pulp small B-cell lymphomas (SDRPBL), and 30 of diffuse large B-cell lymphoma (DLBCL).
They found that cortactin was expressed in 14 of the 17 CLL samples, all 10 of the HCL samples, and 22 of the 30 DLBCL samples. In contrast, there was no cortactin expression detected in any of either 16 MCL or three SDRPBL samples. The researchers found that 13 of 30 MZL samples had low-level staining. In FL, cortactin was expressed in 2 of the samples but in the remaining 23 cases the researchers found only scattered cortactin-positive lymphoid elements of non–B-cell lineage.
The investigators also found that cortactin expression in CLL correlated with other CLL-specific markers, and found that expression of two or more of the markers had 89.1% sensitivity, 100% specificity, a 100% positive predictive value, and 90.5% negative predictive value for a diagnosis of CLL.
In addition, they saw that the immunohistochemical results were similar to those for CTTN gene expression assessed by in silico analysis.
The investigators noted that CLL and MCL are challenging to differentiate from one another because of morphologic similarities and partially overlapping immunophenotypes.
“In this context, cortactin expression would strongly sustain a diagnosis of CLL over MCL, particularly in association with other CLL markers (i.e., LEF1 and CD200),” they wrote.
The study was internally supported. The authors declared no conflicts of interest.
SOURCE: Pizzi M et al. Hum Pathol. 2018 Nov 17. doi: 10.1016/j.humpath.2018.10.038.
The presence or absence in tumor cells of cortactin, a cytoskeleton-remodeling adapter protein, may be a marker to help pathologists distinguish between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), investigators suggest.
A study of cortactin expression in tumor samples from patients with B-cell CLL, MCL, and other hematologic malignancies showed that while cortactin was present in 14 of 17 CLL samples, it was not expressed on any of 16 MCL samples, reported Marco Pizzi, MD, PhD, from the University of Padova (Italy) and his colleagues.
“In particular, cortactin may contribute to the differential diagnosis between CLL and MCL, two neoplasms with similar histological features but very different clinical outcome. Further studies are needed to clarify the molecular mechanisms of deranged cortactin expression in MCL and CLL and to investigate any possible relationship between cortactin status and the biological features of these lymphomas,” they wrote in Human Pathology.
Overexpression of cortactin has been reported in several solid tumors, and increased expression of CTTN, the gene encoding for cortactin, has been associated with aggressive, poor prognosis disease, the investigators noted.
To characterize cortactin expression in lymphoid and hematopoietic cells and detect potential associations between cortactin and virulence of hematologic malignancies, the investigators performed immunohistochemical analysis on samples from 131 patients treated at their center. The samples included 17 cases of CLL, 16 of MCL, 25 of follicular lymphoma (FL), 30 of marginal zone lymphoma (MZL), 10 of hairy cell leukemia, three of splenic diffuse red pulp small B-cell lymphomas (SDRPBL), and 30 of diffuse large B-cell lymphoma (DLBCL).
They found that cortactin was expressed in 14 of the 17 CLL samples, all 10 of the HCL samples, and 22 of the 30 DLBCL samples. In contrast, there was no cortactin expression detected in any of either 16 MCL or three SDRPBL samples. The researchers found that 13 of 30 MZL samples had low-level staining. In FL, cortactin was expressed in 2 of the samples but in the remaining 23 cases the researchers found only scattered cortactin-positive lymphoid elements of non–B-cell lineage.
The investigators also found that cortactin expression in CLL correlated with other CLL-specific markers, and found that expression of two or more of the markers had 89.1% sensitivity, 100% specificity, a 100% positive predictive value, and 90.5% negative predictive value for a diagnosis of CLL.
In addition, they saw that the immunohistochemical results were similar to those for CTTN gene expression assessed by in silico analysis.
The investigators noted that CLL and MCL are challenging to differentiate from one another because of morphologic similarities and partially overlapping immunophenotypes.
“In this context, cortactin expression would strongly sustain a diagnosis of CLL over MCL, particularly in association with other CLL markers (i.e., LEF1 and CD200),” they wrote.
The study was internally supported. The authors declared no conflicts of interest.
SOURCE: Pizzi M et al. Hum Pathol. 2018 Nov 17. doi: 10.1016/j.humpath.2018.10.038.
FROM HUMAN PATHOLOGY
Key clinical point:
Major finding: Cortactin was expressed on 14 of 17 CLL samples vs. none of 16 MCL samples.
Study details: Immunohistochemistry analysis of samples from 131 patients with B-cell lineage non-Hodgkin lymphomas.
Disclosures: The study was internally supported. The authors reported having no conflicts of interest.
Source: Pizzi M et al. Hum Pathol. 2018 Nov 17. doi: 10.1016/j.humpath.2018.10.038.
ASH 2018 coming attractions look at the big picture
In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering
Shorter R-CHOP regimen for DLBCL
Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).
Ibrutinib mastery in CLL
Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).
The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.
Anemia support in beta-thalassemia, MDS
In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.
The investigators report that the experimental agent was “generally well tolerated” (abstract 163).
“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.
Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.
“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.
Worth the wait
The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.
Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.
The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).
Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).
“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.
On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).
“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.
Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).
The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6).
In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering
Shorter R-CHOP regimen for DLBCL
Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).
Ibrutinib mastery in CLL
Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).
The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.
Anemia support in beta-thalassemia, MDS
In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.
The investigators report that the experimental agent was “generally well tolerated” (abstract 163).
“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.
Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.
“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.
Worth the wait
The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.
Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.
The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).
Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).
“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.
On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).
“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.
Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).
The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6).
In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering
Shorter R-CHOP regimen for DLBCL
Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).
Ibrutinib mastery in CLL
Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).
The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.
Anemia support in beta-thalassemia, MDS
In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.
The investigators report that the experimental agent was “generally well tolerated” (abstract 163).
“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.
Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.
“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.
Worth the wait
The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.
Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.
The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).
Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).
“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.
On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).
“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.
Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).
The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6).
Rituximab biosimilar looks equivalent in follicular lymphoma
The rituximab biosimilar CT-P10 has equivalent efficacy, compared with rituximab, and is well tolerated in the treatment of low–tumor-burden follicular lymphoma, according to results from a multinational, randomized, phase 3 study.
Overall response after 7 months of treatment exceeded 80% for patients assigned to CT-P10 and for those assigned to rituximab, investigators reported in the Lancet Haematology.
Adverse event profiles were comparable for rituximab and the biosimilar over that time period, while pharmacokinetics, pharmacodynamics, and immunogenicity were likewise comparable between arms, according to investigators.
“Thus, CT-P10 monotherapy is suggested as a new therapeutic option for patients with low–tumor-burden follicular lymphoma,” wrote senior author Larry W Kwak, MD, PhD, of the Comprehensive Cancer Center, City of Hope, Duarte, Calif., and his colleagues.
CT-P10, the first rituximab biosimilar to be authorized by the European Medicines Agency, has been recommended for approval in the United States by the Food and Drug Administration’s Oncologic Drugs Advisory Committee.
If approved by the FDA, CT-P10 would be the first rituximab biosimilar available in the United States, according to the company, which noted three proposed indications in non-Hodgkin lymphoma.
In the current randomized, double-blind, parallel-group, phase 3 trial, 258 patients with stage II-IV low–tumor-burden follicular lymphoma were randomly assigned to CT-P10 (130 patients) or rituximab sourced in the United States (128 patients).
Treatment consisted of an induction period of intravenous CT-P10 or rituximab weekly for 4 weeks, while patients experiencing disease control went on to a maintenance phase with their assigned treatment given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
The primary endpoint of the study was overall response at 7 months, defined as a complete response, unconfirmed complete response, or partial response.
Overall response was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab at 7 months, Dr. Kwak and his colleagues reported.
The two treatments were deemed therapeutically equivalent, as illustrated by 90% confidence intervals within a prespecified equivalence margin of 17%, investigators said.
The most common treatment-emergent adverse events in either group were infusion-related reactions, which were of grade 1-2, except for one grade 3 reaction reported in the CT-P10 group, according to the report. Other common adverse events were upper respiratory tract infections and fatigue.
Serious adverse events were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
The availability of a rituximab biosimilar is anticipated to reduce the cost of treatment and improve patient access, according to investigators.
Introduction of CT-P10 in the European Union was projected to save between 90 and 150 million euros over a year, enabling more than 12,500 new patients to be treated with the biosimilar, according to results of a budget impact analysis investigators cited in their report.
“Widespread adoption of a rituximab biosimilar could have a substantial effect on health care budgets and might also have effects at a societal level,” Dr. Kwak and his coauthors said in the report.
The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Dr. Kwak and several other coinvestigators not employed by Celltrion reported disclosures related to the company. Other disclosures provided related to Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
SOURCE: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.
The rituximab biosimilar CT-P10 has equivalent efficacy, compared with rituximab, and is well tolerated in the treatment of low–tumor-burden follicular lymphoma, according to results from a multinational, randomized, phase 3 study.
Overall response after 7 months of treatment exceeded 80% for patients assigned to CT-P10 and for those assigned to rituximab, investigators reported in the Lancet Haematology.
Adverse event profiles were comparable for rituximab and the biosimilar over that time period, while pharmacokinetics, pharmacodynamics, and immunogenicity were likewise comparable between arms, according to investigators.
“Thus, CT-P10 monotherapy is suggested as a new therapeutic option for patients with low–tumor-burden follicular lymphoma,” wrote senior author Larry W Kwak, MD, PhD, of the Comprehensive Cancer Center, City of Hope, Duarte, Calif., and his colleagues.
CT-P10, the first rituximab biosimilar to be authorized by the European Medicines Agency, has been recommended for approval in the United States by the Food and Drug Administration’s Oncologic Drugs Advisory Committee.
If approved by the FDA, CT-P10 would be the first rituximab biosimilar available in the United States, according to the company, which noted three proposed indications in non-Hodgkin lymphoma.
In the current randomized, double-blind, parallel-group, phase 3 trial, 258 patients with stage II-IV low–tumor-burden follicular lymphoma were randomly assigned to CT-P10 (130 patients) or rituximab sourced in the United States (128 patients).
Treatment consisted of an induction period of intravenous CT-P10 or rituximab weekly for 4 weeks, while patients experiencing disease control went on to a maintenance phase with their assigned treatment given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
The primary endpoint of the study was overall response at 7 months, defined as a complete response, unconfirmed complete response, or partial response.
Overall response was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab at 7 months, Dr. Kwak and his colleagues reported.
The two treatments were deemed therapeutically equivalent, as illustrated by 90% confidence intervals within a prespecified equivalence margin of 17%, investigators said.
The most common treatment-emergent adverse events in either group were infusion-related reactions, which were of grade 1-2, except for one grade 3 reaction reported in the CT-P10 group, according to the report. Other common adverse events were upper respiratory tract infections and fatigue.
Serious adverse events were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
The availability of a rituximab biosimilar is anticipated to reduce the cost of treatment and improve patient access, according to investigators.
Introduction of CT-P10 in the European Union was projected to save between 90 and 150 million euros over a year, enabling more than 12,500 new patients to be treated with the biosimilar, according to results of a budget impact analysis investigators cited in their report.
“Widespread adoption of a rituximab biosimilar could have a substantial effect on health care budgets and might also have effects at a societal level,” Dr. Kwak and his coauthors said in the report.
The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Dr. Kwak and several other coinvestigators not employed by Celltrion reported disclosures related to the company. Other disclosures provided related to Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
SOURCE: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.
The rituximab biosimilar CT-P10 has equivalent efficacy, compared with rituximab, and is well tolerated in the treatment of low–tumor-burden follicular lymphoma, according to results from a multinational, randomized, phase 3 study.
Overall response after 7 months of treatment exceeded 80% for patients assigned to CT-P10 and for those assigned to rituximab, investigators reported in the Lancet Haematology.
Adverse event profiles were comparable for rituximab and the biosimilar over that time period, while pharmacokinetics, pharmacodynamics, and immunogenicity were likewise comparable between arms, according to investigators.
“Thus, CT-P10 monotherapy is suggested as a new therapeutic option for patients with low–tumor-burden follicular lymphoma,” wrote senior author Larry W Kwak, MD, PhD, of the Comprehensive Cancer Center, City of Hope, Duarte, Calif., and his colleagues.
CT-P10, the first rituximab biosimilar to be authorized by the European Medicines Agency, has been recommended for approval in the United States by the Food and Drug Administration’s Oncologic Drugs Advisory Committee.
If approved by the FDA, CT-P10 would be the first rituximab biosimilar available in the United States, according to the company, which noted three proposed indications in non-Hodgkin lymphoma.
In the current randomized, double-blind, parallel-group, phase 3 trial, 258 patients with stage II-IV low–tumor-burden follicular lymphoma were randomly assigned to CT-P10 (130 patients) or rituximab sourced in the United States (128 patients).
Treatment consisted of an induction period of intravenous CT-P10 or rituximab weekly for 4 weeks, while patients experiencing disease control went on to a maintenance phase with their assigned treatment given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
The primary endpoint of the study was overall response at 7 months, defined as a complete response, unconfirmed complete response, or partial response.
Overall response was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab at 7 months, Dr. Kwak and his colleagues reported.
The two treatments were deemed therapeutically equivalent, as illustrated by 90% confidence intervals within a prespecified equivalence margin of 17%, investigators said.
The most common treatment-emergent adverse events in either group were infusion-related reactions, which were of grade 1-2, except for one grade 3 reaction reported in the CT-P10 group, according to the report. Other common adverse events were upper respiratory tract infections and fatigue.
Serious adverse events were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
The availability of a rituximab biosimilar is anticipated to reduce the cost of treatment and improve patient access, according to investigators.
Introduction of CT-P10 in the European Union was projected to save between 90 and 150 million euros over a year, enabling more than 12,500 new patients to be treated with the biosimilar, according to results of a budget impact analysis investigators cited in their report.
“Widespread adoption of a rituximab biosimilar could have a substantial effect on health care budgets and might also have effects at a societal level,” Dr. Kwak and his coauthors said in the report.
The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Dr. Kwak and several other coinvestigators not employed by Celltrion reported disclosures related to the company. Other disclosures provided related to Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
SOURCE: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.
FROM LANCET HAEMATOLOGY
Key clinical point:
Major finding: Overall response after 7 months of treatment was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab.
Study details: Analysis of 258 patients randomized to CT-P10 or rituximab in a phase 3, double-blind, parallel-group trial.
Disclosures: The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Other study coauthors reported disclosures related to Celltrion, Novartis, Roche, AbbVie, Celgene, and Takeda, among other companies.
Source: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.
FDA expands approval of brentuximab vedotin to PTCL
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
NHL patients report fear, isolation during chemo
Patients undergoing chemotherapy for non-Hodgkin lymphoma (NHL) report feeling isolated and uncertain, and in some cases suicidal, according to a small qualitative study.
Daren Chircop, MS, and Josianne Scerri, PhD, of the University of Malta performed in-depth interviews with four men and two women with aggressive NHL who were midway through CHOP chemotherapy at a cancer center in Malta.
The findings, which were published in the European Journal of Oncology Nursing, highlight three overarching themes. Patients reported that they felt like they were living on an “emotional roller coaster, they were becoming dependent on others, and they were facing an uncertain future.
Specifically, being admitted to a hospital for chemotherapy brought on a fear of the unknown. While being released from the hospital caused anxiety about what would happen once they left the around-the-clock care of doctors and nurses.
The side effects of the chemotherapy – particularly fatigue – led to feelings of being dependent of others and a fear of becoming a burden to families, and even to nurses.
For four of the patients, who were not allowed to leave their hospital rooms during treatment, they reported feeling “imprisoned” and isolated.
Uncertainty was another common theme, with all of the patients reporting that they did not know if they would recover from their cancer and feeling that they had no control over the future.
Additionally, two of the patients experienced suicidal thoughts related to the side effects of treatment.
While many of these feelings are similar to reports by patients with other types of cancer, the researchers suggested that NHL patients experience a greater sense of isolation because they may not be able to leave their hospital rooms while undergoing chemotherapy due to a higher risk of infection.
“There is the need for ongoing psychological support to be available throughout the treatment period,” the researchers wrote. “Moreover, as NHL patients are affected both physically and emotionally whilst undergoing chemotherapy, the engagement of these individuals in some physical activity could be of benefit to them.”
There was no outside funding for the study and the researchers reported having no financial disclosures.
SOURCE: Chircop D et al. Eur J Oncol Nurs. 2018 Aug;35:117-21.
Patients undergoing chemotherapy for non-Hodgkin lymphoma (NHL) report feeling isolated and uncertain, and in some cases suicidal, according to a small qualitative study.
Daren Chircop, MS, and Josianne Scerri, PhD, of the University of Malta performed in-depth interviews with four men and two women with aggressive NHL who were midway through CHOP chemotherapy at a cancer center in Malta.
The findings, which were published in the European Journal of Oncology Nursing, highlight three overarching themes. Patients reported that they felt like they were living on an “emotional roller coaster, they were becoming dependent on others, and they were facing an uncertain future.
Specifically, being admitted to a hospital for chemotherapy brought on a fear of the unknown. While being released from the hospital caused anxiety about what would happen once they left the around-the-clock care of doctors and nurses.
The side effects of the chemotherapy – particularly fatigue – led to feelings of being dependent of others and a fear of becoming a burden to families, and even to nurses.
For four of the patients, who were not allowed to leave their hospital rooms during treatment, they reported feeling “imprisoned” and isolated.
Uncertainty was another common theme, with all of the patients reporting that they did not know if they would recover from their cancer and feeling that they had no control over the future.
Additionally, two of the patients experienced suicidal thoughts related to the side effects of treatment.
While many of these feelings are similar to reports by patients with other types of cancer, the researchers suggested that NHL patients experience a greater sense of isolation because they may not be able to leave their hospital rooms while undergoing chemotherapy due to a higher risk of infection.
“There is the need for ongoing psychological support to be available throughout the treatment period,” the researchers wrote. “Moreover, as NHL patients are affected both physically and emotionally whilst undergoing chemotherapy, the engagement of these individuals in some physical activity could be of benefit to them.”
There was no outside funding for the study and the researchers reported having no financial disclosures.
SOURCE: Chircop D et al. Eur J Oncol Nurs. 2018 Aug;35:117-21.
Patients undergoing chemotherapy for non-Hodgkin lymphoma (NHL) report feeling isolated and uncertain, and in some cases suicidal, according to a small qualitative study.
Daren Chircop, MS, and Josianne Scerri, PhD, of the University of Malta performed in-depth interviews with four men and two women with aggressive NHL who were midway through CHOP chemotherapy at a cancer center in Malta.
The findings, which were published in the European Journal of Oncology Nursing, highlight three overarching themes. Patients reported that they felt like they were living on an “emotional roller coaster, they were becoming dependent on others, and they were facing an uncertain future.
Specifically, being admitted to a hospital for chemotherapy brought on a fear of the unknown. While being released from the hospital caused anxiety about what would happen once they left the around-the-clock care of doctors and nurses.
The side effects of the chemotherapy – particularly fatigue – led to feelings of being dependent of others and a fear of becoming a burden to families, and even to nurses.
For four of the patients, who were not allowed to leave their hospital rooms during treatment, they reported feeling “imprisoned” and isolated.
Uncertainty was another common theme, with all of the patients reporting that they did not know if they would recover from their cancer and feeling that they had no control over the future.
Additionally, two of the patients experienced suicidal thoughts related to the side effects of treatment.
While many of these feelings are similar to reports by patients with other types of cancer, the researchers suggested that NHL patients experience a greater sense of isolation because they may not be able to leave their hospital rooms while undergoing chemotherapy due to a higher risk of infection.
“There is the need for ongoing psychological support to be available throughout the treatment period,” the researchers wrote. “Moreover, as NHL patients are affected both physically and emotionally whilst undergoing chemotherapy, the engagement of these individuals in some physical activity could be of benefit to them.”
There was no outside funding for the study and the researchers reported having no financial disclosures.
SOURCE: Chircop D et al. Eur J Oncol Nurs. 2018 Aug;35:117-21.
FROM EUROPEAN JOURNAL OF ONCOLOGY NURSING
Key clinical point:
Major finding: Patients reported three themes while undergoing chemotherapy: living an emotional roller coaster, becoming dependent on others, and facing an uncertain future.
Study details: A qualitative study of six adults patients with non-Hodgkin lymphoma who were undergoing chemotherapy.
Disclosures: There was no outside funding for the study and the researchers reported having no financial disclosures.
Source: Chircop D et al. Eur J Oncol Nurs. 2018 Aug;35:117-21.