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Basiliximab/BEAM may improve post-ASCT outcomes in PTCL
LA JOLLA, CALIF. – Combining a radio-labeled, anti-CD25, monoclonal antibody with BEAM chemotherapy appears to be an effective and safe conditioning regimen prior to autologous stem cell transplant in patients with peripheral T-cell lymphoma (PTCL), investigators report.
In a phase 1 trial, median progression-free survival (PFS) was 10.6 months for patients treated with the yttrium-90–labeled, chimeric, anti-CD25 antibody basiliximab (Simulect) at one of three dose levels plus standard dose BEAM (carmustine, etoposide, cytarabine, and melphalan), said Jasmine Zain, MD, of the City of Hope Medical Center in Duarte, Calif.
There have been no significant cases of delayed transplant engraftment or unexpected increases in either mucositis or infectious complications, she said at the annual T-cell Lymphoma Forum.
“With standard conditioning, I think the best outcome we have seen is that at 5 years we have about 45% to 50% event-free survival, depending on the histology,” she said. “So we’re hoping we will surpass that.”
The first patient to receive a transplant in the study was treated in July 2015, and since most relapses in this patient population tend to occur within 2 years of transplant, the investigators expect that they will get a better idea of the results in the near future, Dr. Zain said.
PTCL generally has a poor prognosis, and many centers have turned to high-dose therapy followed by autologous stem cell transplant as a consolidation strategy for patients who are in their first or subsequent complete remissions, as well as for patients with relapsed or refractory disease.
“We in this field consider autologous stem cell transplant to be not curative for PTCL. It is true that some patients will achieve long-term remission and even long-term survival,” she said. ”But overall, even with long-term data, it seems like most patients will eventually relapse.”
The goal of the ongoing study is to determine whether adding basiliximab to BEAM could improve outcomes in the long run.
Unlike ibritumomab tiuxetan (Zevalin) – an yttrium-90–labeled antibody that’s been combined with rituximab to target CD20 in relapsed or refractory low-grade follicular B-cell non-Hodgkin lymphoma – basiliximab is targeted to CD25, which is preferentially expressed on T cells.
Basiliximab has been shown to inhibit growth of human anaplastic large cell lymphoma (ALCL) tumors and improve survival in mice bearing human tumor xenografts.
Because the beta particles that basiliximab emits cannot be detected on conventional scans, the antibody is also labeled with an indium-111 radiotracer for purposes of tracking.
At the time of Dr. Zain’s presentation, 13 patients ranging from 19 to 77 years of age were enrolled in the phase 1 trial. The patients were assigned to receive basiliximab at a dose of either 0.4, 0.5, or 0.6 mCi/kg in combination with standard dose BEAM.
The first patient treated had delayed engraftment of platelets; all subsequent patients had engraftment as expected.
There were no grade 3 or 4 toxicities at any dose level and no treatment-related mortality. The most frequent toxicity was grade 2 stomatitis, which occurred in three patients each in the 0.4 and 0.6 miC/kg levels and in four patients at the 0.5 miC/kg level of basiliximab. There were no dose-limiting toxicities.
As of the data cutoff, three patients have experienced relapses, and two of those patients died from disease progression. The times from transplant to relapse were 301 days and 218 days in the two patients who died, and it was 108 days in the third patient.
Dose expansion is continuing in the study, with an additional seven patients scheduled for treatment at the 0.6 miC/kg dose, Dr. Zain said.
Dr. Zain did not report information on conflicts of interest. The study is supported by City of Hope Medical Center and the National Cancer Institute. The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
SOURCE: Zain J et al. TCLF 2018.
LA JOLLA, CALIF. – Combining a radio-labeled, anti-CD25, monoclonal antibody with BEAM chemotherapy appears to be an effective and safe conditioning regimen prior to autologous stem cell transplant in patients with peripheral T-cell lymphoma (PTCL), investigators report.
In a phase 1 trial, median progression-free survival (PFS) was 10.6 months for patients treated with the yttrium-90–labeled, chimeric, anti-CD25 antibody basiliximab (Simulect) at one of three dose levels plus standard dose BEAM (carmustine, etoposide, cytarabine, and melphalan), said Jasmine Zain, MD, of the City of Hope Medical Center in Duarte, Calif.
There have been no significant cases of delayed transplant engraftment or unexpected increases in either mucositis or infectious complications, she said at the annual T-cell Lymphoma Forum.
“With standard conditioning, I think the best outcome we have seen is that at 5 years we have about 45% to 50% event-free survival, depending on the histology,” she said. “So we’re hoping we will surpass that.”
The first patient to receive a transplant in the study was treated in July 2015, and since most relapses in this patient population tend to occur within 2 years of transplant, the investigators expect that they will get a better idea of the results in the near future, Dr. Zain said.
PTCL generally has a poor prognosis, and many centers have turned to high-dose therapy followed by autologous stem cell transplant as a consolidation strategy for patients who are in their first or subsequent complete remissions, as well as for patients with relapsed or refractory disease.
“We in this field consider autologous stem cell transplant to be not curative for PTCL. It is true that some patients will achieve long-term remission and even long-term survival,” she said. ”But overall, even with long-term data, it seems like most patients will eventually relapse.”
The goal of the ongoing study is to determine whether adding basiliximab to BEAM could improve outcomes in the long run.
Unlike ibritumomab tiuxetan (Zevalin) – an yttrium-90–labeled antibody that’s been combined with rituximab to target CD20 in relapsed or refractory low-grade follicular B-cell non-Hodgkin lymphoma – basiliximab is targeted to CD25, which is preferentially expressed on T cells.
Basiliximab has been shown to inhibit growth of human anaplastic large cell lymphoma (ALCL) tumors and improve survival in mice bearing human tumor xenografts.
Because the beta particles that basiliximab emits cannot be detected on conventional scans, the antibody is also labeled with an indium-111 radiotracer for purposes of tracking.
At the time of Dr. Zain’s presentation, 13 patients ranging from 19 to 77 years of age were enrolled in the phase 1 trial. The patients were assigned to receive basiliximab at a dose of either 0.4, 0.5, or 0.6 mCi/kg in combination with standard dose BEAM.
The first patient treated had delayed engraftment of platelets; all subsequent patients had engraftment as expected.
There were no grade 3 or 4 toxicities at any dose level and no treatment-related mortality. The most frequent toxicity was grade 2 stomatitis, which occurred in three patients each in the 0.4 and 0.6 miC/kg levels and in four patients at the 0.5 miC/kg level of basiliximab. There were no dose-limiting toxicities.
As of the data cutoff, three patients have experienced relapses, and two of those patients died from disease progression. The times from transplant to relapse were 301 days and 218 days in the two patients who died, and it was 108 days in the third patient.
Dose expansion is continuing in the study, with an additional seven patients scheduled for treatment at the 0.6 miC/kg dose, Dr. Zain said.
Dr. Zain did not report information on conflicts of interest. The study is supported by City of Hope Medical Center and the National Cancer Institute. The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
SOURCE: Zain J et al. TCLF 2018.
LA JOLLA, CALIF. – Combining a radio-labeled, anti-CD25, monoclonal antibody with BEAM chemotherapy appears to be an effective and safe conditioning regimen prior to autologous stem cell transplant in patients with peripheral T-cell lymphoma (PTCL), investigators report.
In a phase 1 trial, median progression-free survival (PFS) was 10.6 months for patients treated with the yttrium-90–labeled, chimeric, anti-CD25 antibody basiliximab (Simulect) at one of three dose levels plus standard dose BEAM (carmustine, etoposide, cytarabine, and melphalan), said Jasmine Zain, MD, of the City of Hope Medical Center in Duarte, Calif.
There have been no significant cases of delayed transplant engraftment or unexpected increases in either mucositis or infectious complications, she said at the annual T-cell Lymphoma Forum.
“With standard conditioning, I think the best outcome we have seen is that at 5 years we have about 45% to 50% event-free survival, depending on the histology,” she said. “So we’re hoping we will surpass that.”
The first patient to receive a transplant in the study was treated in July 2015, and since most relapses in this patient population tend to occur within 2 years of transplant, the investigators expect that they will get a better idea of the results in the near future, Dr. Zain said.
PTCL generally has a poor prognosis, and many centers have turned to high-dose therapy followed by autologous stem cell transplant as a consolidation strategy for patients who are in their first or subsequent complete remissions, as well as for patients with relapsed or refractory disease.
“We in this field consider autologous stem cell transplant to be not curative for PTCL. It is true that some patients will achieve long-term remission and even long-term survival,” she said. ”But overall, even with long-term data, it seems like most patients will eventually relapse.”
The goal of the ongoing study is to determine whether adding basiliximab to BEAM could improve outcomes in the long run.
Unlike ibritumomab tiuxetan (Zevalin) – an yttrium-90–labeled antibody that’s been combined with rituximab to target CD20 in relapsed or refractory low-grade follicular B-cell non-Hodgkin lymphoma – basiliximab is targeted to CD25, which is preferentially expressed on T cells.
Basiliximab has been shown to inhibit growth of human anaplastic large cell lymphoma (ALCL) tumors and improve survival in mice bearing human tumor xenografts.
Because the beta particles that basiliximab emits cannot be detected on conventional scans, the antibody is also labeled with an indium-111 radiotracer for purposes of tracking.
At the time of Dr. Zain’s presentation, 13 patients ranging from 19 to 77 years of age were enrolled in the phase 1 trial. The patients were assigned to receive basiliximab at a dose of either 0.4, 0.5, or 0.6 mCi/kg in combination with standard dose BEAM.
The first patient treated had delayed engraftment of platelets; all subsequent patients had engraftment as expected.
There were no grade 3 or 4 toxicities at any dose level and no treatment-related mortality. The most frequent toxicity was grade 2 stomatitis, which occurred in three patients each in the 0.4 and 0.6 miC/kg levels and in four patients at the 0.5 miC/kg level of basiliximab. There were no dose-limiting toxicities.
As of the data cutoff, three patients have experienced relapses, and two of those patients died from disease progression. The times from transplant to relapse were 301 days and 218 days in the two patients who died, and it was 108 days in the third patient.
Dose expansion is continuing in the study, with an additional seven patients scheduled for treatment at the 0.6 miC/kg dose, Dr. Zain said.
Dr. Zain did not report information on conflicts of interest. The study is supported by City of Hope Medical Center and the National Cancer Institute. The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
SOURCE: Zain J et al. TCLF 2018.
REPORTING FROM TLCF 2018
Key clinical point:
Major finding: Median progression-free survival posttransplant was 10.6 months.
Study details: A phase 1, dose-finding trial in 13 patients with PTCL.
Disclosures: Dr. Zain did not report information on conflicts of interest. The study is supported by City of Hope Medical Center, Duarte, Calif., and the National Cancer Institute.
Source: Zain J et al. TLCF 2018.
A view from the bridge to transplant for PTCL
LA JOLLA, CALIF. – For patients with relapsed peripheral T-cell lymphoma, allogeneic stem cell transplants offer the best chance for achieving remission or even a cure, making the choice of therapies as bridges to transplant essential for getting there.
“The goal is to get to transplant with a curative intent. In our hands, that’s mostly allo[geneic] and mostly in the relapsed setting,” Steven M. Horwitz, MD, from the lymphoma service at Memorial Sloan Kettering Cancer Center, New York, said at the annual T-cell Lymphoma Forum. “The best bridge to transplant is the one that gets you across safely.”
“They’d finish ICE, get a 3- or 4-week break, get a transplant, leave the hospital 3 or 4 weeks later, and then usually by their first repeat scan, at least on average, those patients had already progressed, so we sort of cooled to the idea of auto transplant and started preferentially looking at allo if we were going to treat with curative intent in the relapsed setting,” he said.
In contrast to autologous SCT, the Memorial Sloan Kettering experience with allogeneic SCT for 65 patients with relapsed PTCL showed a 2-year overall survival rate of 59%, 2-year PFS rate of 48%, and a median PFS of 20.3 months. However, the rate of 1-year transplant-related mortality was still relatively high, at 17%, Dr. Horwitz acknowledged (ASH 2015. Abstract 4392).
An updated retrospective analysis of the center’s experience treating mature T-cell lymphoma patients with allogeneic SCT, also presented at the 2018 T-cell Lymphoma Forum, showed that disease status at transplant was one of the most important predictors of outcome. Median posttransplant PFS for patients in complete remission (CR) at the time of transplant was 61.3 months, compared with 11.4 months for patients in partial remission, 14 months for patients with stable disease, and 6.4 months for patients with disease progression (TCLF 2018. Abstract TM18_9).
“I think we can probably infer from [this] that CR not only gives you a better outcome with allo, but probably increases your chance that you get to an allo,” he said.
In the randomized phase 3 Lumiere study comparing the Aurora A kinase inhibitor alisertib with investigators’ choice of therapy in relapsed/refractory PTCL, alisertib was associated with a CR rate of 19%, whereas pralatrexate, gemcitabine, and romidepsin were associated with CR rates of 29%, 23%, and 33%, respectively, putting them on par with combination chemotherapy.
“I think many of us prefer some of the newer single agents because we’re really going for a durable maintenance of disease control rather than short-term bridge to transplant, but these drugs can provide adequate responses to transition over,” he said.
Better approaches by subtype?
The subtype of PTCL also appears to matter. Three approved agents for relapsed/refractory PTCL – belinostat (Beleodaq), romidepsin (Istodax), and pralatrexate (Folotyn) – are associated with CR rates of 11%, 15%, and 11%, respectively. But one PTCL subtype, anaplastic large cell lymphoma, appears particularly sensitive to treatment with brentuximab vedotin (Adcetris), with CR rates of 59%, Dr. Horwitz noted.
In a 2014 study, investigators reported that of the nine patients with anaplastic large cell lymphoma positive for anaplastic lymphoma kinase and treated with the anaplastic lymphoma kinase inhibitor crizotinib (Xalkori), all had a CR, with response durations stretching pasting 40 months in one patient, and past 30 months in two others (J Natl Cancer Inst. 2014 Feb;106[2]:djt378).
A different subtype, natural killer/T-cell lymphoma, was shown to be responsive to immunotherapy with pembrolizumab (Keytruda) in seven patients, with CRs in five and partial remissions in two. Responses to pembrolizumab in this PTCL subtype may be adequately long for getting patients to transplant, Dr. Horwitz said.
For some patients with angioimmunoblastic T-cell lymphoma, therapy with epigenetic modifying agents, such as decitabine or a combination of romidepsin and lenalidomide (Revlimid), with or without carfilzomib (Kyprolis), may also be effective bridges to transplant, based on the best available evidence.
Timing may also matter
Dr. Horwitz cautioned that for patients with cutaneous T-cell lymphoma, the investigational agent mogamulizumab, which was shown in the MAVORIC (Study of KW-0761 versus Vorinostat in Relapsed/Refractory CTCL) trial to offer significantly better PFS compared with vorinostat (Zolinza), also appears to increase the chance that patients will develop high-risk, potentially fatal graft vs. host disease posttransplant.
The risk appears to be slightly lower among patients who received the last dose of mogamulizumab more than 50 days before undergoing SCT, he noted.
Although there is no strong evidence to support it, Dr. Horwitz noted that the timing of most other therapies may also be important to the success of SCT. “I think we have seen that when patients have a big [long] break before transplant, the relapse rate is high, and I have a personal preference for using regimens that you can continue up close to transplant, because I think we lose [fewer] patients getting ready for that,” he said.
Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – For patients with relapsed peripheral T-cell lymphoma, allogeneic stem cell transplants offer the best chance for achieving remission or even a cure, making the choice of therapies as bridges to transplant essential for getting there.
“The goal is to get to transplant with a curative intent. In our hands, that’s mostly allo[geneic] and mostly in the relapsed setting,” Steven M. Horwitz, MD, from the lymphoma service at Memorial Sloan Kettering Cancer Center, New York, said at the annual T-cell Lymphoma Forum. “The best bridge to transplant is the one that gets you across safely.”
“They’d finish ICE, get a 3- or 4-week break, get a transplant, leave the hospital 3 or 4 weeks later, and then usually by their first repeat scan, at least on average, those patients had already progressed, so we sort of cooled to the idea of auto transplant and started preferentially looking at allo if we were going to treat with curative intent in the relapsed setting,” he said.
In contrast to autologous SCT, the Memorial Sloan Kettering experience with allogeneic SCT for 65 patients with relapsed PTCL showed a 2-year overall survival rate of 59%, 2-year PFS rate of 48%, and a median PFS of 20.3 months. However, the rate of 1-year transplant-related mortality was still relatively high, at 17%, Dr. Horwitz acknowledged (ASH 2015. Abstract 4392).
An updated retrospective analysis of the center’s experience treating mature T-cell lymphoma patients with allogeneic SCT, also presented at the 2018 T-cell Lymphoma Forum, showed that disease status at transplant was one of the most important predictors of outcome. Median posttransplant PFS for patients in complete remission (CR) at the time of transplant was 61.3 months, compared with 11.4 months for patients in partial remission, 14 months for patients with stable disease, and 6.4 months for patients with disease progression (TCLF 2018. Abstract TM18_9).
“I think we can probably infer from [this] that CR not only gives you a better outcome with allo, but probably increases your chance that you get to an allo,” he said.
In the randomized phase 3 Lumiere study comparing the Aurora A kinase inhibitor alisertib with investigators’ choice of therapy in relapsed/refractory PTCL, alisertib was associated with a CR rate of 19%, whereas pralatrexate, gemcitabine, and romidepsin were associated with CR rates of 29%, 23%, and 33%, respectively, putting them on par with combination chemotherapy.
“I think many of us prefer some of the newer single agents because we’re really going for a durable maintenance of disease control rather than short-term bridge to transplant, but these drugs can provide adequate responses to transition over,” he said.
Better approaches by subtype?
The subtype of PTCL also appears to matter. Three approved agents for relapsed/refractory PTCL – belinostat (Beleodaq), romidepsin (Istodax), and pralatrexate (Folotyn) – are associated with CR rates of 11%, 15%, and 11%, respectively. But one PTCL subtype, anaplastic large cell lymphoma, appears particularly sensitive to treatment with brentuximab vedotin (Adcetris), with CR rates of 59%, Dr. Horwitz noted.
In a 2014 study, investigators reported that of the nine patients with anaplastic large cell lymphoma positive for anaplastic lymphoma kinase and treated with the anaplastic lymphoma kinase inhibitor crizotinib (Xalkori), all had a CR, with response durations stretching pasting 40 months in one patient, and past 30 months in two others (J Natl Cancer Inst. 2014 Feb;106[2]:djt378).
A different subtype, natural killer/T-cell lymphoma, was shown to be responsive to immunotherapy with pembrolizumab (Keytruda) in seven patients, with CRs in five and partial remissions in two. Responses to pembrolizumab in this PTCL subtype may be adequately long for getting patients to transplant, Dr. Horwitz said.
For some patients with angioimmunoblastic T-cell lymphoma, therapy with epigenetic modifying agents, such as decitabine or a combination of romidepsin and lenalidomide (Revlimid), with or without carfilzomib (Kyprolis), may also be effective bridges to transplant, based on the best available evidence.
Timing may also matter
Dr. Horwitz cautioned that for patients with cutaneous T-cell lymphoma, the investigational agent mogamulizumab, which was shown in the MAVORIC (Study of KW-0761 versus Vorinostat in Relapsed/Refractory CTCL) trial to offer significantly better PFS compared with vorinostat (Zolinza), also appears to increase the chance that patients will develop high-risk, potentially fatal graft vs. host disease posttransplant.
The risk appears to be slightly lower among patients who received the last dose of mogamulizumab more than 50 days before undergoing SCT, he noted.
Although there is no strong evidence to support it, Dr. Horwitz noted that the timing of most other therapies may also be important to the success of SCT. “I think we have seen that when patients have a big [long] break before transplant, the relapse rate is high, and I have a personal preference for using regimens that you can continue up close to transplant, because I think we lose [fewer] patients getting ready for that,” he said.
Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – For patients with relapsed peripheral T-cell lymphoma, allogeneic stem cell transplants offer the best chance for achieving remission or even a cure, making the choice of therapies as bridges to transplant essential for getting there.
“The goal is to get to transplant with a curative intent. In our hands, that’s mostly allo[geneic] and mostly in the relapsed setting,” Steven M. Horwitz, MD, from the lymphoma service at Memorial Sloan Kettering Cancer Center, New York, said at the annual T-cell Lymphoma Forum. “The best bridge to transplant is the one that gets you across safely.”
“They’d finish ICE, get a 3- or 4-week break, get a transplant, leave the hospital 3 or 4 weeks later, and then usually by their first repeat scan, at least on average, those patients had already progressed, so we sort of cooled to the idea of auto transplant and started preferentially looking at allo if we were going to treat with curative intent in the relapsed setting,” he said.
In contrast to autologous SCT, the Memorial Sloan Kettering experience with allogeneic SCT for 65 patients with relapsed PTCL showed a 2-year overall survival rate of 59%, 2-year PFS rate of 48%, and a median PFS of 20.3 months. However, the rate of 1-year transplant-related mortality was still relatively high, at 17%, Dr. Horwitz acknowledged (ASH 2015. Abstract 4392).
An updated retrospective analysis of the center’s experience treating mature T-cell lymphoma patients with allogeneic SCT, also presented at the 2018 T-cell Lymphoma Forum, showed that disease status at transplant was one of the most important predictors of outcome. Median posttransplant PFS for patients in complete remission (CR) at the time of transplant was 61.3 months, compared with 11.4 months for patients in partial remission, 14 months for patients with stable disease, and 6.4 months for patients with disease progression (TCLF 2018. Abstract TM18_9).
“I think we can probably infer from [this] that CR not only gives you a better outcome with allo, but probably increases your chance that you get to an allo,” he said.
In the randomized phase 3 Lumiere study comparing the Aurora A kinase inhibitor alisertib with investigators’ choice of therapy in relapsed/refractory PTCL, alisertib was associated with a CR rate of 19%, whereas pralatrexate, gemcitabine, and romidepsin were associated with CR rates of 29%, 23%, and 33%, respectively, putting them on par with combination chemotherapy.
“I think many of us prefer some of the newer single agents because we’re really going for a durable maintenance of disease control rather than short-term bridge to transplant, but these drugs can provide adequate responses to transition over,” he said.
Better approaches by subtype?
The subtype of PTCL also appears to matter. Three approved agents for relapsed/refractory PTCL – belinostat (Beleodaq), romidepsin (Istodax), and pralatrexate (Folotyn) – are associated with CR rates of 11%, 15%, and 11%, respectively. But one PTCL subtype, anaplastic large cell lymphoma, appears particularly sensitive to treatment with brentuximab vedotin (Adcetris), with CR rates of 59%, Dr. Horwitz noted.
In a 2014 study, investigators reported that of the nine patients with anaplastic large cell lymphoma positive for anaplastic lymphoma kinase and treated with the anaplastic lymphoma kinase inhibitor crizotinib (Xalkori), all had a CR, with response durations stretching pasting 40 months in one patient, and past 30 months in two others (J Natl Cancer Inst. 2014 Feb;106[2]:djt378).
A different subtype, natural killer/T-cell lymphoma, was shown to be responsive to immunotherapy with pembrolizumab (Keytruda) in seven patients, with CRs in five and partial remissions in two. Responses to pembrolizumab in this PTCL subtype may be adequately long for getting patients to transplant, Dr. Horwitz said.
For some patients with angioimmunoblastic T-cell lymphoma, therapy with epigenetic modifying agents, such as decitabine or a combination of romidepsin and lenalidomide (Revlimid), with or without carfilzomib (Kyprolis), may also be effective bridges to transplant, based on the best available evidence.
Timing may also matter
Dr. Horwitz cautioned that for patients with cutaneous T-cell lymphoma, the investigational agent mogamulizumab, which was shown in the MAVORIC (Study of KW-0761 versus Vorinostat in Relapsed/Refractory CTCL) trial to offer significantly better PFS compared with vorinostat (Zolinza), also appears to increase the chance that patients will develop high-risk, potentially fatal graft vs. host disease posttransplant.
The risk appears to be slightly lower among patients who received the last dose of mogamulizumab more than 50 days before undergoing SCT, he noted.
Although there is no strong evidence to support it, Dr. Horwitz noted that the timing of most other therapies may also be important to the success of SCT. “I think we have seen that when patients have a big [long] break before transplant, the relapse rate is high, and I have a personal preference for using regimens that you can continue up close to transplant, because I think we lose [fewer] patients getting ready for that,” he said.
Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
EXPERT ANALYSIS FROM TCLF 2018
Getting hematologic cancer drugs on the fast track
LA JOLLA, CALIF. – The words “rapid approval” and “Food and Drug Administration” rarely appear in the same sentence. But despite that perception, the pace of hematologic drug development has been accelerating over the last several years, according to an agency staffer.
“FDA is committed toward the expedited development of safe and effective therapies for serious and life-threatening diseases,” R. Angelo de Claro, MD, of the FDA’s Office of Hematology and Oncology Products said at the annual T-cell Lymphoma Forum. Dr. de Claro outlined his agency’s efforts to accelerate approval of drugs for treatment of T-cell malignancies.
Hematologic drug bonanza
In 2017 alone, the FDA approved 17 agents for new or expanded indications for hematologic malignancies, including brentuximab vedotin (Adcetris) for anaplastic large cell lymphoma (ALCL) and CD30-positive mycosis fungoides (MF).
Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or primary cutaneous ALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.
Dr. de Claro noted that in the ALCANZA trial, patients were required to have one or more biopsy samples with at least 10% CD30 expression, but among 184 patients with MF screened for the trial, 32% were ineligible because of less than 10% CD30 expression. The FDA therefore requested additional efficacy data for patients with MF with less than 10% CD30 expression and accepted data from two investigator-sponsored trials showing that 35 patients with MF expressing CD30 on 1%-9% of cells had a 31% overall response rate, whereas two patients with no CD30 expression did not have responses.
Who minds the store
Hematology products are under the aegis of the FDA’s Oncology Center of Excellence. Oversight includes benign hematology products, as well as products for hematologic cancers and hematologic support. Hematology and oncology toxicology is monitored by pharmacologists and toxicologists in a separate division, he explained.
“The Oncology Center of Excellence was formally launched in 2017 as part of the 21st century CURES Act. The mission of the Oncology Center of Excellence is to achieve patient-centered regulatory decision making through innovation and collaboration,” he said.
Getting the nod
To get approved, a new therapy requires “substantial” evidence of efficacy and safety. Regular approvals are based on either direct measures of clinical benefits – how a patient “feels, functions, or survives” – or a measure of the effect of a drug on an established surrogate endpoint.
For an accelerated approval, developers must be able to show evidence on either a surrogate or intermediate clinical endpoint that the agent is reasonably likely to offer a benefit and be a meaningful improvement over available therapies. Postapproval trials may be needed to verify the proposed benefits.
FDA accelerated approval programs include:
- Fast track. The pathway requires nonclinical or clinical data demonstrating the potential for addressing an unmet need.
- Breakthrough therapy. This pathway requires preliminary clinical evidence demonstrating substantial improvement over existing available therapies.
- Priority review. These are agents that, if approved, would provide significant improvements in safety or effectiveness.
- Accelerated approval. The drug must demonstrate an effect on an “endpoint reasonably likely to predict clinical benefit over available therapies.”
Dr. de Claro is employed by the FDA. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – The words “rapid approval” and “Food and Drug Administration” rarely appear in the same sentence. But despite that perception, the pace of hematologic drug development has been accelerating over the last several years, according to an agency staffer.
“FDA is committed toward the expedited development of safe and effective therapies for serious and life-threatening diseases,” R. Angelo de Claro, MD, of the FDA’s Office of Hematology and Oncology Products said at the annual T-cell Lymphoma Forum. Dr. de Claro outlined his agency’s efforts to accelerate approval of drugs for treatment of T-cell malignancies.
Hematologic drug bonanza
In 2017 alone, the FDA approved 17 agents for new or expanded indications for hematologic malignancies, including brentuximab vedotin (Adcetris) for anaplastic large cell lymphoma (ALCL) and CD30-positive mycosis fungoides (MF).
Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or primary cutaneous ALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.
Dr. de Claro noted that in the ALCANZA trial, patients were required to have one or more biopsy samples with at least 10% CD30 expression, but among 184 patients with MF screened for the trial, 32% were ineligible because of less than 10% CD30 expression. The FDA therefore requested additional efficacy data for patients with MF with less than 10% CD30 expression and accepted data from two investigator-sponsored trials showing that 35 patients with MF expressing CD30 on 1%-9% of cells had a 31% overall response rate, whereas two patients with no CD30 expression did not have responses.
Who minds the store
Hematology products are under the aegis of the FDA’s Oncology Center of Excellence. Oversight includes benign hematology products, as well as products for hematologic cancers and hematologic support. Hematology and oncology toxicology is monitored by pharmacologists and toxicologists in a separate division, he explained.
“The Oncology Center of Excellence was formally launched in 2017 as part of the 21st century CURES Act. The mission of the Oncology Center of Excellence is to achieve patient-centered regulatory decision making through innovation and collaboration,” he said.
Getting the nod
To get approved, a new therapy requires “substantial” evidence of efficacy and safety. Regular approvals are based on either direct measures of clinical benefits – how a patient “feels, functions, or survives” – or a measure of the effect of a drug on an established surrogate endpoint.
For an accelerated approval, developers must be able to show evidence on either a surrogate or intermediate clinical endpoint that the agent is reasonably likely to offer a benefit and be a meaningful improvement over available therapies. Postapproval trials may be needed to verify the proposed benefits.
FDA accelerated approval programs include:
- Fast track. The pathway requires nonclinical or clinical data demonstrating the potential for addressing an unmet need.
- Breakthrough therapy. This pathway requires preliminary clinical evidence demonstrating substantial improvement over existing available therapies.
- Priority review. These are agents that, if approved, would provide significant improvements in safety or effectiveness.
- Accelerated approval. The drug must demonstrate an effect on an “endpoint reasonably likely to predict clinical benefit over available therapies.”
Dr. de Claro is employed by the FDA. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – The words “rapid approval” and “Food and Drug Administration” rarely appear in the same sentence. But despite that perception, the pace of hematologic drug development has been accelerating over the last several years, according to an agency staffer.
“FDA is committed toward the expedited development of safe and effective therapies for serious and life-threatening diseases,” R. Angelo de Claro, MD, of the FDA’s Office of Hematology and Oncology Products said at the annual T-cell Lymphoma Forum. Dr. de Claro outlined his agency’s efforts to accelerate approval of drugs for treatment of T-cell malignancies.
Hematologic drug bonanza
In 2017 alone, the FDA approved 17 agents for new or expanded indications for hematologic malignancies, including brentuximab vedotin (Adcetris) for anaplastic large cell lymphoma (ALCL) and CD30-positive mycosis fungoides (MF).
Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or primary cutaneous ALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.
Dr. de Claro noted that in the ALCANZA trial, patients were required to have one or more biopsy samples with at least 10% CD30 expression, but among 184 patients with MF screened for the trial, 32% were ineligible because of less than 10% CD30 expression. The FDA therefore requested additional efficacy data for patients with MF with less than 10% CD30 expression and accepted data from two investigator-sponsored trials showing that 35 patients with MF expressing CD30 on 1%-9% of cells had a 31% overall response rate, whereas two patients with no CD30 expression did not have responses.
Who minds the store
Hematology products are under the aegis of the FDA’s Oncology Center of Excellence. Oversight includes benign hematology products, as well as products for hematologic cancers and hematologic support. Hematology and oncology toxicology is monitored by pharmacologists and toxicologists in a separate division, he explained.
“The Oncology Center of Excellence was formally launched in 2017 as part of the 21st century CURES Act. The mission of the Oncology Center of Excellence is to achieve patient-centered regulatory decision making through innovation and collaboration,” he said.
Getting the nod
To get approved, a new therapy requires “substantial” evidence of efficacy and safety. Regular approvals are based on either direct measures of clinical benefits – how a patient “feels, functions, or survives” – or a measure of the effect of a drug on an established surrogate endpoint.
For an accelerated approval, developers must be able to show evidence on either a surrogate or intermediate clinical endpoint that the agent is reasonably likely to offer a benefit and be a meaningful improvement over available therapies. Postapproval trials may be needed to verify the proposed benefits.
FDA accelerated approval programs include:
- Fast track. The pathway requires nonclinical or clinical data demonstrating the potential for addressing an unmet need.
- Breakthrough therapy. This pathway requires preliminary clinical evidence demonstrating substantial improvement over existing available therapies.
- Priority review. These are agents that, if approved, would provide significant improvements in safety or effectiveness.
- Accelerated approval. The drug must demonstrate an effect on an “endpoint reasonably likely to predict clinical benefit over available therapies.”
Dr. de Claro is employed by the FDA. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
EXPERT ANALYSIS FROM TCLF 2018
T-cell lymphoma therapies on the horizon
LA JOLLA, CALIF. – There are several biologic compounds in early clinical development for treatment of patients with T-cell lymphomas, including an antibody-drug conjugate, novel immune checkpoint inhibitor, and bi-specific antibody.
These investigational agents show promising single-agent activity and have the potential to improve clinical responses when combined with combination chemotherapy regimens or other treatments, Ahmed Sawas, MD, of the Center for Lymphoid Malignancies at Columbia University, New York, said at the annual T-cell Lymphoma Forum.
AGS67E: Antibody-drug conjugate
AGS67E is an antibody-drug conjugate targeted against CD37, a transmembrane protein preferentially expressed on malignant B cells, T cells, and acute myeloid leukemia cells. In a study published in 2015 in Molecular Cancer Therapeutics, investigators from Agensys (an affiliate of Astellas Pharma) reported that this compound bound to more than 80% of patient-derived T cells in vitro (Mol Cancer Ther. 2015;14[7]:1650-60).
In a phase 1 dose-escalation study reported at the 2017 International Conference on Malignant Lymphoma in Lugano, Switzerland, Dr. Sawas and his colleagues found that patients with B-cell and T-cell malignancies, including cutaneous T-cell lymphoma and peripheral T-cell lymphoma, tolerated the drug well when it was delivered both with or without growth factor. Neutropenia was the most frequent adverse event and dose-limiting toxicity.
The drug showed single-agent activity in 16 of 53 patients with heavily pretreated non-Hodgkin lymphoma, including a partial response in one of two patients with cutaneous T-cell lymphoma, and partial responses in two of four patients with peripheral T-cell lymphoma. There were no complete responses at any of three dose levels of the drug, with or without growth factor.
One patient, a 75-year-old man with stage IVB mycosis fungoides who had disease progression on prior therapy with methotrexate, romidepsin, bendamustine, whole-body irradiation, liposomal doxorubicin, pralatrexate, and pembrolizumab experienced significant reduction in tumor burden and resolution of lymph node involvement after three 3-week cycles of therapy with AGS67E. The patient had a deepening of the response with additional cycles, and remained on therapy for 30 cycles until he experienced disease progression.
TTI-621: Tuck in, macrophages
TT1-621 is a molecule with two functions: It acts as an immune checkpoint inhibitor by blocking CD47, which binds to signal-regulatory protein alpha to produce an antiphagocytic or “do not eat” signal. TTI-621 does not, however, bind to CD47-positive erythrocytes.
In addition to blocking CD47 and the do-not-eat signal, TTI-621 delivers an activating signal to macrophages through Fc gamma receptors, telling them, in effect, “bon appétit.”
In a study presented at the 2017 annual meeting of the American Society of Hematology (Abstract 4076), investigators from City of Hope in Duarte, Calif., and other centers reported that a single direct intratumoral injection of TTI-621 was associated with significant antitumor activity in patients with relapsed or refractory mycosis fungoides and Sézary syndrome, with one of nine patients having a complete response in the injected lesion, and five having decreases in tumor size and/or circulating Sézary cells.
Patients appeared to tolerate this agent very well, with 1 of 18 having a grade 3 increase in white blood cell count. The most commonly reported side effects were fatigue, chills, decreased appetite, headache, injection site pain, and generalized pruritus, each occurring in 3 of the 18 patients.
TTI-621 injection was associated with rapid declines in Composite Assessment of Index Lesion Severity scores in dose-finding studies in patients with heavily pretreated cutaneous T-cell lymphoma, Dr. Sawas said.
AFM13: Two for the price of one
AFM13 is a bi-specific antibody that binds to CD30, which is expressed on anaplastic large cell lymphoma cells, as well as Reed-Sternberg cells of classical Hodgkin lymphoma. This antibody also engages CD16A-positive cells, resulting in lysis of CD30-positive tumor cells. It is a specific recruiter of natural killer cells, and does not bind to neutrophils.
In an early biologic effects study of this agent in CD30-positive lymphoid malignancies with cutaneous presentation, Dr. Sawas and his colleagues observed an early response and regression of cutaneous anaplastic large cell lymphoma lesions in a heavily pretreated patient, with progression occurring when the patient went off therapy, and tumors that diminished on reinitiation of therapy that sustained beyond a second discontinuation of therapy. This patient had measurable reductions in lymphoma burden on PET CT scans and improvements in cutaneous lesions. Dr. Sawas did not present safety data for this agent.
AGS67E studies are supported by Agensys. TTI-621 studies are supported by Trillium Therapeutics. The AFM13 study is supported by Columbia University, with Dr. Sawas listed as the sponsor. He did not report potential conflicts of interests. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – There are several biologic compounds in early clinical development for treatment of patients with T-cell lymphomas, including an antibody-drug conjugate, novel immune checkpoint inhibitor, and bi-specific antibody.
These investigational agents show promising single-agent activity and have the potential to improve clinical responses when combined with combination chemotherapy regimens or other treatments, Ahmed Sawas, MD, of the Center for Lymphoid Malignancies at Columbia University, New York, said at the annual T-cell Lymphoma Forum.
AGS67E: Antibody-drug conjugate
AGS67E is an antibody-drug conjugate targeted against CD37, a transmembrane protein preferentially expressed on malignant B cells, T cells, and acute myeloid leukemia cells. In a study published in 2015 in Molecular Cancer Therapeutics, investigators from Agensys (an affiliate of Astellas Pharma) reported that this compound bound to more than 80% of patient-derived T cells in vitro (Mol Cancer Ther. 2015;14[7]:1650-60).
In a phase 1 dose-escalation study reported at the 2017 International Conference on Malignant Lymphoma in Lugano, Switzerland, Dr. Sawas and his colleagues found that patients with B-cell and T-cell malignancies, including cutaneous T-cell lymphoma and peripheral T-cell lymphoma, tolerated the drug well when it was delivered both with or without growth factor. Neutropenia was the most frequent adverse event and dose-limiting toxicity.
The drug showed single-agent activity in 16 of 53 patients with heavily pretreated non-Hodgkin lymphoma, including a partial response in one of two patients with cutaneous T-cell lymphoma, and partial responses in two of four patients with peripheral T-cell lymphoma. There were no complete responses at any of three dose levels of the drug, with or without growth factor.
One patient, a 75-year-old man with stage IVB mycosis fungoides who had disease progression on prior therapy with methotrexate, romidepsin, bendamustine, whole-body irradiation, liposomal doxorubicin, pralatrexate, and pembrolizumab experienced significant reduction in tumor burden and resolution of lymph node involvement after three 3-week cycles of therapy with AGS67E. The patient had a deepening of the response with additional cycles, and remained on therapy for 30 cycles until he experienced disease progression.
TTI-621: Tuck in, macrophages
TT1-621 is a molecule with two functions: It acts as an immune checkpoint inhibitor by blocking CD47, which binds to signal-regulatory protein alpha to produce an antiphagocytic or “do not eat” signal. TTI-621 does not, however, bind to CD47-positive erythrocytes.
In addition to blocking CD47 and the do-not-eat signal, TTI-621 delivers an activating signal to macrophages through Fc gamma receptors, telling them, in effect, “bon appétit.”
In a study presented at the 2017 annual meeting of the American Society of Hematology (Abstract 4076), investigators from City of Hope in Duarte, Calif., and other centers reported that a single direct intratumoral injection of TTI-621 was associated with significant antitumor activity in patients with relapsed or refractory mycosis fungoides and Sézary syndrome, with one of nine patients having a complete response in the injected lesion, and five having decreases in tumor size and/or circulating Sézary cells.
Patients appeared to tolerate this agent very well, with 1 of 18 having a grade 3 increase in white blood cell count. The most commonly reported side effects were fatigue, chills, decreased appetite, headache, injection site pain, and generalized pruritus, each occurring in 3 of the 18 patients.
TTI-621 injection was associated with rapid declines in Composite Assessment of Index Lesion Severity scores in dose-finding studies in patients with heavily pretreated cutaneous T-cell lymphoma, Dr. Sawas said.
AFM13: Two for the price of one
AFM13 is a bi-specific antibody that binds to CD30, which is expressed on anaplastic large cell lymphoma cells, as well as Reed-Sternberg cells of classical Hodgkin lymphoma. This antibody also engages CD16A-positive cells, resulting in lysis of CD30-positive tumor cells. It is a specific recruiter of natural killer cells, and does not bind to neutrophils.
In an early biologic effects study of this agent in CD30-positive lymphoid malignancies with cutaneous presentation, Dr. Sawas and his colleagues observed an early response and regression of cutaneous anaplastic large cell lymphoma lesions in a heavily pretreated patient, with progression occurring when the patient went off therapy, and tumors that diminished on reinitiation of therapy that sustained beyond a second discontinuation of therapy. This patient had measurable reductions in lymphoma burden on PET CT scans and improvements in cutaneous lesions. Dr. Sawas did not present safety data for this agent.
AGS67E studies are supported by Agensys. TTI-621 studies are supported by Trillium Therapeutics. The AFM13 study is supported by Columbia University, with Dr. Sawas listed as the sponsor. He did not report potential conflicts of interests. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – There are several biologic compounds in early clinical development for treatment of patients with T-cell lymphomas, including an antibody-drug conjugate, novel immune checkpoint inhibitor, and bi-specific antibody.
These investigational agents show promising single-agent activity and have the potential to improve clinical responses when combined with combination chemotherapy regimens or other treatments, Ahmed Sawas, MD, of the Center for Lymphoid Malignancies at Columbia University, New York, said at the annual T-cell Lymphoma Forum.
AGS67E: Antibody-drug conjugate
AGS67E is an antibody-drug conjugate targeted against CD37, a transmembrane protein preferentially expressed on malignant B cells, T cells, and acute myeloid leukemia cells. In a study published in 2015 in Molecular Cancer Therapeutics, investigators from Agensys (an affiliate of Astellas Pharma) reported that this compound bound to more than 80% of patient-derived T cells in vitro (Mol Cancer Ther. 2015;14[7]:1650-60).
In a phase 1 dose-escalation study reported at the 2017 International Conference on Malignant Lymphoma in Lugano, Switzerland, Dr. Sawas and his colleagues found that patients with B-cell and T-cell malignancies, including cutaneous T-cell lymphoma and peripheral T-cell lymphoma, tolerated the drug well when it was delivered both with or without growth factor. Neutropenia was the most frequent adverse event and dose-limiting toxicity.
The drug showed single-agent activity in 16 of 53 patients with heavily pretreated non-Hodgkin lymphoma, including a partial response in one of two patients with cutaneous T-cell lymphoma, and partial responses in two of four patients with peripheral T-cell lymphoma. There were no complete responses at any of three dose levels of the drug, with or without growth factor.
One patient, a 75-year-old man with stage IVB mycosis fungoides who had disease progression on prior therapy with methotrexate, romidepsin, bendamustine, whole-body irradiation, liposomal doxorubicin, pralatrexate, and pembrolizumab experienced significant reduction in tumor burden and resolution of lymph node involvement after three 3-week cycles of therapy with AGS67E. The patient had a deepening of the response with additional cycles, and remained on therapy for 30 cycles until he experienced disease progression.
TTI-621: Tuck in, macrophages
TT1-621 is a molecule with two functions: It acts as an immune checkpoint inhibitor by blocking CD47, which binds to signal-regulatory protein alpha to produce an antiphagocytic or “do not eat” signal. TTI-621 does not, however, bind to CD47-positive erythrocytes.
In addition to blocking CD47 and the do-not-eat signal, TTI-621 delivers an activating signal to macrophages through Fc gamma receptors, telling them, in effect, “bon appétit.”
In a study presented at the 2017 annual meeting of the American Society of Hematology (Abstract 4076), investigators from City of Hope in Duarte, Calif., and other centers reported that a single direct intratumoral injection of TTI-621 was associated with significant antitumor activity in patients with relapsed or refractory mycosis fungoides and Sézary syndrome, with one of nine patients having a complete response in the injected lesion, and five having decreases in tumor size and/or circulating Sézary cells.
Patients appeared to tolerate this agent very well, with 1 of 18 having a grade 3 increase in white blood cell count. The most commonly reported side effects were fatigue, chills, decreased appetite, headache, injection site pain, and generalized pruritus, each occurring in 3 of the 18 patients.
TTI-621 injection was associated with rapid declines in Composite Assessment of Index Lesion Severity scores in dose-finding studies in patients with heavily pretreated cutaneous T-cell lymphoma, Dr. Sawas said.
AFM13: Two for the price of one
AFM13 is a bi-specific antibody that binds to CD30, which is expressed on anaplastic large cell lymphoma cells, as well as Reed-Sternberg cells of classical Hodgkin lymphoma. This antibody also engages CD16A-positive cells, resulting in lysis of CD30-positive tumor cells. It is a specific recruiter of natural killer cells, and does not bind to neutrophils.
In an early biologic effects study of this agent in CD30-positive lymphoid malignancies with cutaneous presentation, Dr. Sawas and his colleagues observed an early response and regression of cutaneous anaplastic large cell lymphoma lesions in a heavily pretreated patient, with progression occurring when the patient went off therapy, and tumors that diminished on reinitiation of therapy that sustained beyond a second discontinuation of therapy. This patient had measurable reductions in lymphoma burden on PET CT scans and improvements in cutaneous lesions. Dr. Sawas did not present safety data for this agent.
AGS67E studies are supported by Agensys. TTI-621 studies are supported by Trillium Therapeutics. The AFM13 study is supported by Columbia University, with Dr. Sawas listed as the sponsor. He did not report potential conflicts of interests. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
EXPERT ANALYSIS FROM TCLF 2018
MAVORIC: Mogamulizumab tops vorinostat in pretreated CTCL
ATLANTA – Intravenous treatment with mogamulizumab, an investigational antibody targeting CC chemokine receptor 4, more than doubled progression-free survival (PFS), compared with oral vorinostat in a phase 3 trial of 372 patients with heavily pretreated cutaneous T-cell lymphoma (CTCL).
After a median of three treatment cycles, median PFS with mogamulizumab was 7.7 months vs. 3.1 months with vorinostat (hazard ratio, 0.53; 95% confidence interval, 0.41-0.69; P less than .0001), Youn H. Kim, MD, reported at the annual meeting of the American Society of Hematology.
, said Dr. Kim, the Joanne and Peter Haas, Jr. Professor for Cutaneous Lymphoma Research at Stanford (Calif.) University. Adverse effects, such as infusion reactions, were expected and manageable, she added.
Mogamulizumab is approved in Japan for treating CTCL and received an FDA breakthrough therapy designation in August 2017.
Based on audits so far, the agency might green-light mogamulizumab for previously treated CTCL by early 2018 – its first approval in the United States, Dr. Kim said in an interview.
Cutaneous T-cell lymphoma responds poorly to treatments that work in other, more common types of non-Hodgkin lymphoma. Moreover, extensive disease can destroy quality of life.
“There’s a major psychosocial impact because if you’re infected, you smell bad,” Dr. Kim said during a press briefing. “Itch is very severe – patients often cannot sleep because of it.”
Mogamulizumab is a humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4), which facilitates trafficking of lymphocytes to skin and other organs. It is defucosylated, augmenting its toxicity against malignant T cells. In a prior phase 1/2 study in the United States, mogamulizumab showed a tolerable safety profile and a 37% overall response rate – “a good response, considering that other CTCL drugs are usually in the 30% range,” Dr. Kim said.
For the phase 3 study (MAVORIC), 372 patients with previously treated stage IB to stage IVB CTCL (mycosis fungoides or Sézary syndrome) without large-cell transformation received mogamulizumab (1.0 mg/kg IV weekly for 28 days; days 1 and 15 of subsequent 28-day cycles) or vorinostat (400 mg per oral daily). Treatment continued until disease progression or intolerable toxicity. Researchers evaluated PFS based on a global composite response score that covers the skin, blood, lymph nodes, and viscera, in accordance with international consensus guidelines (J Clin Oncol. 2011 Jun 20;29(18):2598-607; doi: 10.1200/JCO.2010.32.0630).
Treatment groups resembled each other at baseline. Most had received three systemic therapies for CTCL, and some had received as many as 18. Median duration of response was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. Patients tended to respond to mogamulizumab 2 months sooner than to vorinostat (3.3 vs. 5.1 months), Dr. Kim said.
Mogamulizumab also significantly improved quality of life on the Skindex-29 Symptoms (P less than .05), Skindex-29 Function (P less than 05), and FACT-G Functional Well-Being (P less than .05) quality of life scales, which is part of what earned it a breakthrough therapy designation, Dr. Kim said.
MAVORIC is the largest randomized study to compare systemic therapies in CTCL and the first to use PFS as the primary endpoint, Dr. Kim noted. Patients’ level of CCR4 expression was not a criterion for enrollment because CCR4 is consistently and highly expressed in this disease, she noted. Thus, using mogamulizumab to treat CTCL in the United States would not require CCR4 testing.
Joseph M. Connors, MD, who specializes in lymphoid cancers at the BC Cancer Agency, a division of the British Columbia Provincial Health Services Authority, and who was not involved in the study, agreed that these data represent real headway in treating CTCL.
“I can state unequivocally that we just haven’t had effective therapy for CTCL,” he said at the press briefing. “We’ve had treatments that might help patients feel somewhat better, but we’ve had no consensus on a treatment that is right for this disease. These data provide an opportunity to have that consensus. They could create a platform for making further progress.”
Kyowa Kirin Pharmaceutical Development provided funding. Dr. Kim disclosed research and advisory relationships with Kyowa Kirin and ties to Millennium Pharmaceuticals, Seattle Genetics, Soligenix, and other companies.
SOURCE: Kim YH et al. ASH 2017 Abstract 817.
ATLANTA – Intravenous treatment with mogamulizumab, an investigational antibody targeting CC chemokine receptor 4, more than doubled progression-free survival (PFS), compared with oral vorinostat in a phase 3 trial of 372 patients with heavily pretreated cutaneous T-cell lymphoma (CTCL).
After a median of three treatment cycles, median PFS with mogamulizumab was 7.7 months vs. 3.1 months with vorinostat (hazard ratio, 0.53; 95% confidence interval, 0.41-0.69; P less than .0001), Youn H. Kim, MD, reported at the annual meeting of the American Society of Hematology.
, said Dr. Kim, the Joanne and Peter Haas, Jr. Professor for Cutaneous Lymphoma Research at Stanford (Calif.) University. Adverse effects, such as infusion reactions, were expected and manageable, she added.
Mogamulizumab is approved in Japan for treating CTCL and received an FDA breakthrough therapy designation in August 2017.
Based on audits so far, the agency might green-light mogamulizumab for previously treated CTCL by early 2018 – its first approval in the United States, Dr. Kim said in an interview.
Cutaneous T-cell lymphoma responds poorly to treatments that work in other, more common types of non-Hodgkin lymphoma. Moreover, extensive disease can destroy quality of life.
“There’s a major psychosocial impact because if you’re infected, you smell bad,” Dr. Kim said during a press briefing. “Itch is very severe – patients often cannot sleep because of it.”
Mogamulizumab is a humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4), which facilitates trafficking of lymphocytes to skin and other organs. It is defucosylated, augmenting its toxicity against malignant T cells. In a prior phase 1/2 study in the United States, mogamulizumab showed a tolerable safety profile and a 37% overall response rate – “a good response, considering that other CTCL drugs are usually in the 30% range,” Dr. Kim said.
For the phase 3 study (MAVORIC), 372 patients with previously treated stage IB to stage IVB CTCL (mycosis fungoides or Sézary syndrome) without large-cell transformation received mogamulizumab (1.0 mg/kg IV weekly for 28 days; days 1 and 15 of subsequent 28-day cycles) or vorinostat (400 mg per oral daily). Treatment continued until disease progression or intolerable toxicity. Researchers evaluated PFS based on a global composite response score that covers the skin, blood, lymph nodes, and viscera, in accordance with international consensus guidelines (J Clin Oncol. 2011 Jun 20;29(18):2598-607; doi: 10.1200/JCO.2010.32.0630).
Treatment groups resembled each other at baseline. Most had received three systemic therapies for CTCL, and some had received as many as 18. Median duration of response was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. Patients tended to respond to mogamulizumab 2 months sooner than to vorinostat (3.3 vs. 5.1 months), Dr. Kim said.
Mogamulizumab also significantly improved quality of life on the Skindex-29 Symptoms (P less than .05), Skindex-29 Function (P less than 05), and FACT-G Functional Well-Being (P less than .05) quality of life scales, which is part of what earned it a breakthrough therapy designation, Dr. Kim said.
MAVORIC is the largest randomized study to compare systemic therapies in CTCL and the first to use PFS as the primary endpoint, Dr. Kim noted. Patients’ level of CCR4 expression was not a criterion for enrollment because CCR4 is consistently and highly expressed in this disease, she noted. Thus, using mogamulizumab to treat CTCL in the United States would not require CCR4 testing.
Joseph M. Connors, MD, who specializes in lymphoid cancers at the BC Cancer Agency, a division of the British Columbia Provincial Health Services Authority, and who was not involved in the study, agreed that these data represent real headway in treating CTCL.
“I can state unequivocally that we just haven’t had effective therapy for CTCL,” he said at the press briefing. “We’ve had treatments that might help patients feel somewhat better, but we’ve had no consensus on a treatment that is right for this disease. These data provide an opportunity to have that consensus. They could create a platform for making further progress.”
Kyowa Kirin Pharmaceutical Development provided funding. Dr. Kim disclosed research and advisory relationships with Kyowa Kirin and ties to Millennium Pharmaceuticals, Seattle Genetics, Soligenix, and other companies.
SOURCE: Kim YH et al. ASH 2017 Abstract 817.
ATLANTA – Intravenous treatment with mogamulizumab, an investigational antibody targeting CC chemokine receptor 4, more than doubled progression-free survival (PFS), compared with oral vorinostat in a phase 3 trial of 372 patients with heavily pretreated cutaneous T-cell lymphoma (CTCL).
After a median of three treatment cycles, median PFS with mogamulizumab was 7.7 months vs. 3.1 months with vorinostat (hazard ratio, 0.53; 95% confidence interval, 0.41-0.69; P less than .0001), Youn H. Kim, MD, reported at the annual meeting of the American Society of Hematology.
, said Dr. Kim, the Joanne and Peter Haas, Jr. Professor for Cutaneous Lymphoma Research at Stanford (Calif.) University. Adverse effects, such as infusion reactions, were expected and manageable, she added.
Mogamulizumab is approved in Japan for treating CTCL and received an FDA breakthrough therapy designation in August 2017.
Based on audits so far, the agency might green-light mogamulizumab for previously treated CTCL by early 2018 – its first approval in the United States, Dr. Kim said in an interview.
Cutaneous T-cell lymphoma responds poorly to treatments that work in other, more common types of non-Hodgkin lymphoma. Moreover, extensive disease can destroy quality of life.
“There’s a major psychosocial impact because if you’re infected, you smell bad,” Dr. Kim said during a press briefing. “Itch is very severe – patients often cannot sleep because of it.”
Mogamulizumab is a humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4), which facilitates trafficking of lymphocytes to skin and other organs. It is defucosylated, augmenting its toxicity against malignant T cells. In a prior phase 1/2 study in the United States, mogamulizumab showed a tolerable safety profile and a 37% overall response rate – “a good response, considering that other CTCL drugs are usually in the 30% range,” Dr. Kim said.
For the phase 3 study (MAVORIC), 372 patients with previously treated stage IB to stage IVB CTCL (mycosis fungoides or Sézary syndrome) without large-cell transformation received mogamulizumab (1.0 mg/kg IV weekly for 28 days; days 1 and 15 of subsequent 28-day cycles) or vorinostat (400 mg per oral daily). Treatment continued until disease progression or intolerable toxicity. Researchers evaluated PFS based on a global composite response score that covers the skin, blood, lymph nodes, and viscera, in accordance with international consensus guidelines (J Clin Oncol. 2011 Jun 20;29(18):2598-607; doi: 10.1200/JCO.2010.32.0630).
Treatment groups resembled each other at baseline. Most had received three systemic therapies for CTCL, and some had received as many as 18. Median duration of response was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. Patients tended to respond to mogamulizumab 2 months sooner than to vorinostat (3.3 vs. 5.1 months), Dr. Kim said.
Mogamulizumab also significantly improved quality of life on the Skindex-29 Symptoms (P less than .05), Skindex-29 Function (P less than 05), and FACT-G Functional Well-Being (P less than .05) quality of life scales, which is part of what earned it a breakthrough therapy designation, Dr. Kim said.
MAVORIC is the largest randomized study to compare systemic therapies in CTCL and the first to use PFS as the primary endpoint, Dr. Kim noted. Patients’ level of CCR4 expression was not a criterion for enrollment because CCR4 is consistently and highly expressed in this disease, she noted. Thus, using mogamulizumab to treat CTCL in the United States would not require CCR4 testing.
Joseph M. Connors, MD, who specializes in lymphoid cancers at the BC Cancer Agency, a division of the British Columbia Provincial Health Services Authority, and who was not involved in the study, agreed that these data represent real headway in treating CTCL.
“I can state unequivocally that we just haven’t had effective therapy for CTCL,” he said at the press briefing. “We’ve had treatments that might help patients feel somewhat better, but we’ve had no consensus on a treatment that is right for this disease. These data provide an opportunity to have that consensus. They could create a platform for making further progress.”
Kyowa Kirin Pharmaceutical Development provided funding. Dr. Kim disclosed research and advisory relationships with Kyowa Kirin and ties to Millennium Pharmaceuticals, Seattle Genetics, Soligenix, and other companies.
SOURCE: Kim YH et al. ASH 2017 Abstract 817.
REPORTING FROM ASH 2017
Key clinical point: Mogamulizumab more than doubled median progression-free survival, compared with vorinostat in patients with previously treated cutaneous T-cell lymphoma.
Major finding: Median progression-free survival was 7.7 months vs. 3.1 months (HR, 0.53; 95% CI, 0.41 to 0.69; P less than .0001).
Data source: An open-label phase 3 trial of 372 patients with previously treated cutaneous T-cell lymphoma (MAVORIC).
Disclosures: Kyowa Kirin Pharmaceutical Development provided funding. Dr. Kim disclosed research and advisory relationships with Kyowa Kirin and ties to Millennium Pharmaceuticals, Seattle Genetics, Soligenix, and other companies.
Source: Kim YH et al. ASH 2017 Abstract 817.
FDA approves brentuximab vedotin for primary cutaneous anaplastic large cell lymphoma
Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.
The most common adverse reactions for patients in the brentuximab vedotin arm were anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue, and neutropenia. The most common adverse event leading to discontinuation of brentuximab vedotin was peripheral neuropathy.
The recommended dose of brentuximab vedotin is 1.8 mg/kg up to a maximum of 180 mg/kg as an IV infusion over 30 minutes every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity, the FDA wrote.
Brentuximab vedotin is marketed as Adcetris by Seattle Genetics.
ALCANZA results were presented at ASH 2016 and published in the Lancet in Aug. 5, 2017.
Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.
The most common adverse reactions for patients in the brentuximab vedotin arm were anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue, and neutropenia. The most common adverse event leading to discontinuation of brentuximab vedotin was peripheral neuropathy.
The recommended dose of brentuximab vedotin is 1.8 mg/kg up to a maximum of 180 mg/kg as an IV infusion over 30 minutes every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity, the FDA wrote.
Brentuximab vedotin is marketed as Adcetris by Seattle Genetics.
ALCANZA results were presented at ASH 2016 and published in the Lancet in Aug. 5, 2017.
Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.
The most common adverse reactions for patients in the brentuximab vedotin arm were anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue, and neutropenia. The most common adverse event leading to discontinuation of brentuximab vedotin was peripheral neuropathy.
The recommended dose of brentuximab vedotin is 1.8 mg/kg up to a maximum of 180 mg/kg as an IV infusion over 30 minutes every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity, the FDA wrote.
Brentuximab vedotin is marketed as Adcetris by Seattle Genetics.
ALCANZA results were presented at ASH 2016 and published in the Lancet in Aug. 5, 2017.
Study shows childhood IBD increased cancer risk in adulthood
Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.
The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.
Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register (BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951).
Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.
Primary sclerosing cholangitis was associated with a sixfold greater risk of cancer, ulcerative colitis was associated with a 2.6-fold greater risk, and patients who had had colitis for 10 years or more had a nearly fourfold greater risk of cancer (HR, 3.9).
The study also found that childhood-onset inflammatory bowel disease was associated with an 18-fold greater risk of gastrointestinal cancer, compared with the general population, matched for age, sex, birth year, and county.
The risk was particularly high in patients with ulcerative colitis, who showed a 33-fold higher risk of colorectal cancer, while patients with Crohn’s disease had a nearly 6-fold higher risk.
“Colorectal cancer is a major cause of cancer mortality in the population, and even a moderately increased incidence is likely to have a large effect on patients with inflammatory bowel disease,” wrote Ola Olén, MD, of Karolinska Institutet, Stockholm, and coauthors.
When the researchers looked in more detail at the type of cancers, they saw the greatest increases in risk were for colorectal cancer (HR, 19.5) and small intestinal cancer (HR, 12.8), while the risk of liver cancer was 134 times higher (95% CI, 59.6-382).
The researchers also saw a 2.7-fold increased risk of lymphoid neoplasms associated with childhood inflammatory bowel disease, particularly in individuals with ulcerative colitis or Crohn’s disease. The most common lymphoid neoplasms were non-Hodgkin lymphomas, followed by Hodgkin lymphomas.
Commenting on possible explanations for the associations seen in the study, the authors said that patients with inflammatory bowel disease may have their gastrointestinal cancers diagnosed earlier than the general population because of regular endoscopies.
They also said that thiopurines and TNF inhibitors – both used to treat inflammatory bowel disease – could not be ruled out as a possible cause of the increase in cancer risk, but their study was not powered to pick up such an effect.
“Instead, we suggest that extent and duration of chronic inflammation might be the main driving mechanisms underlying the increased risk of cancer,” they wrote.
The authors noted that their study did not include data on the smoking status of individuals, which could be significant, because smoking is known to reduce the risk of ulcerative colitis and increase the risk of Crohn’s disease and cancer. However, they pointed out that the majority of patients would not have been smoking at the time of their initial inflammatory bowel disease diagnosis, and would have been unlikely to take up the habit after their diagnosis.
With the observation that the risk of cancer in inflammatory bowel disease was higher in patients who were younger when diagnosed with the disease, the authors suggested that age of onset be considered when designing surveillance strategies for cancer in this group.
The Stockholm County Council and the Karolinska Institutet, the Swedish Cancer Society, the Swedish Research Council, and the Swedish Foundation for Strategic Research supported the study. One author received grants from the Swedish Medical Society, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, the Bengt Ihre Research Fellowship in gastroenterology, and the Karolinska Institutet Foundations. No conflicts of interest were declared.
Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.
The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.
Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register (BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951).
Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.
Primary sclerosing cholangitis was associated with a sixfold greater risk of cancer, ulcerative colitis was associated with a 2.6-fold greater risk, and patients who had had colitis for 10 years or more had a nearly fourfold greater risk of cancer (HR, 3.9).
The study also found that childhood-onset inflammatory bowel disease was associated with an 18-fold greater risk of gastrointestinal cancer, compared with the general population, matched for age, sex, birth year, and county.
The risk was particularly high in patients with ulcerative colitis, who showed a 33-fold higher risk of colorectal cancer, while patients with Crohn’s disease had a nearly 6-fold higher risk.
“Colorectal cancer is a major cause of cancer mortality in the population, and even a moderately increased incidence is likely to have a large effect on patients with inflammatory bowel disease,” wrote Ola Olén, MD, of Karolinska Institutet, Stockholm, and coauthors.
When the researchers looked in more detail at the type of cancers, they saw the greatest increases in risk were for colorectal cancer (HR, 19.5) and small intestinal cancer (HR, 12.8), while the risk of liver cancer was 134 times higher (95% CI, 59.6-382).
The researchers also saw a 2.7-fold increased risk of lymphoid neoplasms associated with childhood inflammatory bowel disease, particularly in individuals with ulcerative colitis or Crohn’s disease. The most common lymphoid neoplasms were non-Hodgkin lymphomas, followed by Hodgkin lymphomas.
Commenting on possible explanations for the associations seen in the study, the authors said that patients with inflammatory bowel disease may have their gastrointestinal cancers diagnosed earlier than the general population because of regular endoscopies.
They also said that thiopurines and TNF inhibitors – both used to treat inflammatory bowel disease – could not be ruled out as a possible cause of the increase in cancer risk, but their study was not powered to pick up such an effect.
“Instead, we suggest that extent and duration of chronic inflammation might be the main driving mechanisms underlying the increased risk of cancer,” they wrote.
The authors noted that their study did not include data on the smoking status of individuals, which could be significant, because smoking is known to reduce the risk of ulcerative colitis and increase the risk of Crohn’s disease and cancer. However, they pointed out that the majority of patients would not have been smoking at the time of their initial inflammatory bowel disease diagnosis, and would have been unlikely to take up the habit after their diagnosis.
With the observation that the risk of cancer in inflammatory bowel disease was higher in patients who were younger when diagnosed with the disease, the authors suggested that age of onset be considered when designing surveillance strategies for cancer in this group.
The Stockholm County Council and the Karolinska Institutet, the Swedish Cancer Society, the Swedish Research Council, and the Swedish Foundation for Strategic Research supported the study. One author received grants from the Swedish Medical Society, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, the Bengt Ihre Research Fellowship in gastroenterology, and the Karolinska Institutet Foundations. No conflicts of interest were declared.
Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.
The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.
Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register (BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951).
Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.
Primary sclerosing cholangitis was associated with a sixfold greater risk of cancer, ulcerative colitis was associated with a 2.6-fold greater risk, and patients who had had colitis for 10 years or more had a nearly fourfold greater risk of cancer (HR, 3.9).
The study also found that childhood-onset inflammatory bowel disease was associated with an 18-fold greater risk of gastrointestinal cancer, compared with the general population, matched for age, sex, birth year, and county.
The risk was particularly high in patients with ulcerative colitis, who showed a 33-fold higher risk of colorectal cancer, while patients with Crohn’s disease had a nearly 6-fold higher risk.
“Colorectal cancer is a major cause of cancer mortality in the population, and even a moderately increased incidence is likely to have a large effect on patients with inflammatory bowel disease,” wrote Ola Olén, MD, of Karolinska Institutet, Stockholm, and coauthors.
When the researchers looked in more detail at the type of cancers, they saw the greatest increases in risk were for colorectal cancer (HR, 19.5) and small intestinal cancer (HR, 12.8), while the risk of liver cancer was 134 times higher (95% CI, 59.6-382).
The researchers also saw a 2.7-fold increased risk of lymphoid neoplasms associated with childhood inflammatory bowel disease, particularly in individuals with ulcerative colitis or Crohn’s disease. The most common lymphoid neoplasms were non-Hodgkin lymphomas, followed by Hodgkin lymphomas.
Commenting on possible explanations for the associations seen in the study, the authors said that patients with inflammatory bowel disease may have their gastrointestinal cancers diagnosed earlier than the general population because of regular endoscopies.
They also said that thiopurines and TNF inhibitors – both used to treat inflammatory bowel disease – could not be ruled out as a possible cause of the increase in cancer risk, but their study was not powered to pick up such an effect.
“Instead, we suggest that extent and duration of chronic inflammation might be the main driving mechanisms underlying the increased risk of cancer,” they wrote.
The authors noted that their study did not include data on the smoking status of individuals, which could be significant, because smoking is known to reduce the risk of ulcerative colitis and increase the risk of Crohn’s disease and cancer. However, they pointed out that the majority of patients would not have been smoking at the time of their initial inflammatory bowel disease diagnosis, and would have been unlikely to take up the habit after their diagnosis.
With the observation that the risk of cancer in inflammatory bowel disease was higher in patients who were younger when diagnosed with the disease, the authors suggested that age of onset be considered when designing surveillance strategies for cancer in this group.
The Stockholm County Council and the Karolinska Institutet, the Swedish Cancer Society, the Swedish Research Council, and the Swedish Foundation for Strategic Research supported the study. One author received grants from the Swedish Medical Society, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, the Bengt Ihre Research Fellowship in gastroenterology, and the Karolinska Institutet Foundations. No conflicts of interest were declared.
FROM BMJ
Key clinical point: Childhood inflammatory bowel disease was associated with significant increases in the risk of cancer – particularly gastrointestinal cancer – in later life.
Major finding: Individuals diagnosed with inflammatory bowel disease in childhood have an 18-fold greater risk of gastrointestinal cancer, and a twofold higher risk of any cancer, compared with the general population.
Data source: A cohort study of 9,405 patients with childhood-onset inflammatory bowel disease.
Disclosures: The Stockholm County Council and the Karolinska Institutet, the Swedish Cancer Society, the Swedish Research Council, and the Swedish Foundation for Strategic Research supported the study. One author received grants from the Swedish Medical Society, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, the Bengt Ihre Research Fellowship in gastroenterology, and the Karolinska Institutet Foundations. No conflicts of interest were declared.
Clinical Endpoints in PTCL: The Road Less Traveled
Release Date: August 1, 2017
Expiration Date: July 31, 2018
Note: This activity is no longer available for credit.
Agenda
Developing New Strategic Goals in PTCL (duration 27:00)
Andrei R. Shustov, MD
University of Washington School of Medicine
Fred Hutchinson Cancer Research Center
Seattle, WA, USA
PTCL as a Rare Disease: A Case of Overall Survival (duration 19:00)
Owen A. O’Connor, MD, PhD
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY, USA
Why Might Response Rates Differ Between the East and West? (duration 17:00)
Kensei Tobinai, MD, PhD
National Cancer Center Hospital
Tokyo, Japan
Provided by:
Original activity supported by an educational grant from:
Spectrum Pharmaceuticals
Learning Objectives
At the end of the activity, participants should be able to:
- Explain why progression-free survival is important when treating patients with PTCL
- Determine when overall survival is possible
- Describe the challenges of using matched control analysis in PTCL clinical trials
- Discuss why different response rates to therapy for PTCL may be seen in Asian patients versus North American or European patients and define the possible contributing factors
Target Audience
Hematologists, oncologists, and other clinicians and scientists with an interest in T-cell lymphoma
Statement of Need
This activity explores clinical endpoints in PTCL, the importance of choosing the appropriate ones and the possibility of achieving them. Global and regional differences in PTCL are also explored as they relate to response rates. The presentations highlight the challenges physicians face in treating PTCL patients and recent developments are discussed to help practitioners evaluate the utility of these endpoints in choosing appropriate treatments to improve outcomes in their patients with PTCL.
FACULTY
Faculty
Andrei R. Shustov, MD
Disclosures: Consulting fee: Celgene; BMS
Owen O’Connor, MD, PhD
Disclosures: Consulting fees: Mundipharma; Celgene; Contracted Research: Mundipharma; Spectrum; Celgene; Seattle Genetics; TG Therapeutics; ADCT; Trillium
Kensei Tobinai, MD, PhD
Disclosures: Honoraria: Eisai; HUYA Bioscience International; Janssen; Mundipharma; Takeda; Zenyaku Kogyo; Contracted research: Abbvie; Celgene; Chugai Pharma; Eisai; GlaxoSmithKline; Janssen; Kyowa Hakko Kirin; Mundipharma; Ono Pharmaceutical; SERVIER; Takeda
Permissions
Andrei Shustov presentation
- Slide 7: PTCL Prognosis Is Indicative of Diverse Biology
- Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
- Slide 8: PTCL: Global Epidemiology
- Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
- Slide 9: PTCL: USA Epidemiology (top half)
- Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
- Slide 9: PTCL: USA Epidemiology (bottom half)
- Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
- Slide 10: PTCL Prognosis: Histology x Race (USA)
- Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
- Slide 12: PTCL Prognosis: Clinical Features (top right side)
- Reprinted with permission. © 2013 American Society of Clinical Oncology. All rights reserved.
- Slide 14: PTCL Prognosis: Molecular Classifiers (left side)
- Republished with permission of the American Society of Hematology, from Parilla Castellar ER, et al. Blood 2014;124:1473-1480
- Slide 14: PTCL Prognosis: Molecular Classifiers (right side)
- Republished with permission of the American Society of Hematology, from Iqbal J, et al. Blood 2014;123:2915-2923
- Slide 17: US Epidemiology of PTCL
- Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
- Slides 18-19: Romidepsin in Relapsed/Refractory PTCL
- Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.
- Slides 20-22, 25: Romidepsin in Elderly Patients
- Shustov A, et al. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma 2017 [Epub ahead of print]. Reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com
- Slides 27-28: Belinostat in Relapsed/Refractory PTCL
- Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.
Kensei Tobinai presentation
- Slide 7: Overall Survival of ATL Pts in JCOG 9801
- Reprinted with permission. © 2007 American Society of Clinical Oncology. All rights reserved.
Disclaimer
The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Hemedicus, the supporter, or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.
Release Date: August 1, 2017
Expiration Date: July 31, 2018
Note: This activity is no longer available for credit.
Agenda
Developing New Strategic Goals in PTCL (duration 27:00)
Andrei R. Shustov, MD
University of Washington School of Medicine
Fred Hutchinson Cancer Research Center
Seattle, WA, USA
PTCL as a Rare Disease: A Case of Overall Survival (duration 19:00)
Owen A. O’Connor, MD, PhD
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY, USA
Why Might Response Rates Differ Between the East and West? (duration 17:00)
Kensei Tobinai, MD, PhD
National Cancer Center Hospital
Tokyo, Japan
Provided by:
Original activity supported by an educational grant from:
Spectrum Pharmaceuticals
Learning Objectives
At the end of the activity, participants should be able to:
- Explain why progression-free survival is important when treating patients with PTCL
- Determine when overall survival is possible
- Describe the challenges of using matched control analysis in PTCL clinical trials
- Discuss why different response rates to therapy for PTCL may be seen in Asian patients versus North American or European patients and define the possible contributing factors
Target Audience
Hematologists, oncologists, and other clinicians and scientists with an interest in T-cell lymphoma
Statement of Need
This activity explores clinical endpoints in PTCL, the importance of choosing the appropriate ones and the possibility of achieving them. Global and regional differences in PTCL are also explored as they relate to response rates. The presentations highlight the challenges physicians face in treating PTCL patients and recent developments are discussed to help practitioners evaluate the utility of these endpoints in choosing appropriate treatments to improve outcomes in their patients with PTCL.
FACULTY
Faculty
Andrei R. Shustov, MD
Disclosures: Consulting fee: Celgene; BMS
Owen O’Connor, MD, PhD
Disclosures: Consulting fees: Mundipharma; Celgene; Contracted Research: Mundipharma; Spectrum; Celgene; Seattle Genetics; TG Therapeutics; ADCT; Trillium
Kensei Tobinai, MD, PhD
Disclosures: Honoraria: Eisai; HUYA Bioscience International; Janssen; Mundipharma; Takeda; Zenyaku Kogyo; Contracted research: Abbvie; Celgene; Chugai Pharma; Eisai; GlaxoSmithKline; Janssen; Kyowa Hakko Kirin; Mundipharma; Ono Pharmaceutical; SERVIER; Takeda
Permissions
Andrei Shustov presentation
- Slide 7: PTCL Prognosis Is Indicative of Diverse Biology
- Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
- Slide 8: PTCL: Global Epidemiology
- Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
- Slide 9: PTCL: USA Epidemiology (top half)
- Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
- Slide 9: PTCL: USA Epidemiology (bottom half)
- Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
- Slide 10: PTCL Prognosis: Histology x Race (USA)
- Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
- Slide 12: PTCL Prognosis: Clinical Features (top right side)
- Reprinted with permission. © 2013 American Society of Clinical Oncology. All rights reserved.
- Slide 14: PTCL Prognosis: Molecular Classifiers (left side)
- Republished with permission of the American Society of Hematology, from Parilla Castellar ER, et al. Blood 2014;124:1473-1480
- Slide 14: PTCL Prognosis: Molecular Classifiers (right side)
- Republished with permission of the American Society of Hematology, from Iqbal J, et al. Blood 2014;123:2915-2923
- Slide 17: US Epidemiology of PTCL
- Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
- Slides 18-19: Romidepsin in Relapsed/Refractory PTCL
- Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.
- Slides 20-22, 25: Romidepsin in Elderly Patients
- Shustov A, et al. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma 2017 [Epub ahead of print]. Reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com
- Slides 27-28: Belinostat in Relapsed/Refractory PTCL
- Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.
Kensei Tobinai presentation
- Slide 7: Overall Survival of ATL Pts in JCOG 9801
- Reprinted with permission. © 2007 American Society of Clinical Oncology. All rights reserved.
Disclaimer
The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Hemedicus, the supporter, or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.
Release Date: August 1, 2017
Expiration Date: July 31, 2018
Note: This activity is no longer available for credit.
Agenda
Developing New Strategic Goals in PTCL (duration 27:00)
Andrei R. Shustov, MD
University of Washington School of Medicine
Fred Hutchinson Cancer Research Center
Seattle, WA, USA
PTCL as a Rare Disease: A Case of Overall Survival (duration 19:00)
Owen A. O’Connor, MD, PhD
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY, USA
Why Might Response Rates Differ Between the East and West? (duration 17:00)
Kensei Tobinai, MD, PhD
National Cancer Center Hospital
Tokyo, Japan
Provided by:
Original activity supported by an educational grant from:
Spectrum Pharmaceuticals
Learning Objectives
At the end of the activity, participants should be able to:
- Explain why progression-free survival is important when treating patients with PTCL
- Determine when overall survival is possible
- Describe the challenges of using matched control analysis in PTCL clinical trials
- Discuss why different response rates to therapy for PTCL may be seen in Asian patients versus North American or European patients and define the possible contributing factors
Target Audience
Hematologists, oncologists, and other clinicians and scientists with an interest in T-cell lymphoma
Statement of Need
This activity explores clinical endpoints in PTCL, the importance of choosing the appropriate ones and the possibility of achieving them. Global and regional differences in PTCL are also explored as they relate to response rates. The presentations highlight the challenges physicians face in treating PTCL patients and recent developments are discussed to help practitioners evaluate the utility of these endpoints in choosing appropriate treatments to improve outcomes in their patients with PTCL.
FACULTY
Faculty
Andrei R. Shustov, MD
Disclosures: Consulting fee: Celgene; BMS
Owen O’Connor, MD, PhD
Disclosures: Consulting fees: Mundipharma; Celgene; Contracted Research: Mundipharma; Spectrum; Celgene; Seattle Genetics; TG Therapeutics; ADCT; Trillium
Kensei Tobinai, MD, PhD
Disclosures: Honoraria: Eisai; HUYA Bioscience International; Janssen; Mundipharma; Takeda; Zenyaku Kogyo; Contracted research: Abbvie; Celgene; Chugai Pharma; Eisai; GlaxoSmithKline; Janssen; Kyowa Hakko Kirin; Mundipharma; Ono Pharmaceutical; SERVIER; Takeda
Permissions
Andrei Shustov presentation
- Slide 7: PTCL Prognosis Is Indicative of Diverse Biology
- Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
- Slide 8: PTCL: Global Epidemiology
- Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
- Slide 9: PTCL: USA Epidemiology (top half)
- Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
- Slide 9: PTCL: USA Epidemiology (bottom half)
- Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
- Slide 10: PTCL Prognosis: Histology x Race (USA)
- Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
- Slide 12: PTCL Prognosis: Clinical Features (top right side)
- Reprinted with permission. © 2013 American Society of Clinical Oncology. All rights reserved.
- Slide 14: PTCL Prognosis: Molecular Classifiers (left side)
- Republished with permission of the American Society of Hematology, from Parilla Castellar ER, et al. Blood 2014;124:1473-1480
- Slide 14: PTCL Prognosis: Molecular Classifiers (right side)
- Republished with permission of the American Society of Hematology, from Iqbal J, et al. Blood 2014;123:2915-2923
- Slide 17: US Epidemiology of PTCL
- Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
- Slides 18-19: Romidepsin in Relapsed/Refractory PTCL
- Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.
- Slides 20-22, 25: Romidepsin in Elderly Patients
- Shustov A, et al. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma 2017 [Epub ahead of print]. Reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com
- Slides 27-28: Belinostat in Relapsed/Refractory PTCL
- Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.
Kensei Tobinai presentation
- Slide 7: Overall Survival of ATL Pts in JCOG 9801
- Reprinted with permission. © 2007 American Society of Clinical Oncology. All rights reserved.
Disclaimer
The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Hemedicus, the supporter, or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.
Phase III trial: VZV protects auto-HCT patients
ORLANDO – An inactivated varicella zoster virus vaccine currently in development for adult patients undergoing autologous hematopoietic stem cell transplantation is efficacious and well tolerated, according to findings from a randomized, placebo-controlled, phase III trial.
During the course of the 2 1/2-year pivotal multicenter trial, confirmed herpes zoster infections occurred in 42 of 560 patients who were randomized to receive inactivated varicella zoster virus vaccine (ZVIN) consistency lot (overall incidence of 32.8 cases/1,000 patient-years), compared with 113 of 564 patients who received placebo (overall incidence of 91.8/1,000 patient-years). The estimated vaccine efficacy was 63.8% after adjusting for age and duration of antiviral prophylaxis, Drew J. Winston, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
The vaccine also was effective for reducing moderate and severe herpes zoster pain (estimated vaccine efficacy, 69.5%), for preventing postherpetic neuralgia (estimated vaccine efficacy, 83.7%), and for prevention of herpes zoster–related complications (estimated vaccine efficacy, 73.5%), he noted.
Study subjects were adults aged 18 years or older who were undergoing autologous hematopoietic stem cell transplantation (auto-HCT) for a malignancy or other indication. The most common underlying diseases were lymphoma and multiple myeloma. All patients had a history of varicella infection or were seropositive for varicella zoster virus (VZV) antibody, and had no history of VZV vaccine or herpes zoster infection within the prior year.
They were randomized to receive a four-dose regimen of either ZVIN consistency lot, ZVIN high-antigen lot, or placebo. A group of 106 patients who received the ZVIN high-antigen lot were included in the safety analysis only. The first ZVIN dose was administered about a month before transplantation, and doses two through four were administered about 30, 60, and 90 days after transplantation. About 90% in each group received antiviral agents after transplantation, and the duration of the use of antivirals also was similar in the groups. All patients were followed for the duration of the study, and those who developed herpes zoster were followed for 6 months after onset.
Herpes zoster cases were confirmed by polymerase chain reaction or by blinded endpoint committee adjudication.
Serious adverse events and vaccine-related serious adverse events occurred in a similar proportion of patients in the treatment and placebo groups (32.9% and 32.7%, and 0.8% and 0.9%, respectively). Vaccine-related events were primarily injection-site reactions. Systemic adverse events that occurred up to 28 days after vaccination were mainly gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Pyrexia, oral mucositis, thrombocytopenia, and febrile neutropenia also were reported.
The most common serious adverse events were infectious complications, such as febrile neutropenia and relapse of underlying disease.
The findings are notable, as patients undergoing auto-HCT have an increased risk of developing herpes zoster infection and its complications, including postherpetic neuralgia, secondary bacterial infections, and disseminated VZV infection, as well as an increased risk of hospitalization and mortality, Dr. Winston explained.
Herpes zoster infections are associated primarily with cell-mediated immunity, and in older studies done prior to the routine use of antiviral prophylaxis, the reported incidence in auto-HCT patients was between 16% and 25%. Because of this high risk, current guidelines call for antiviral prophylaxis during auto-HCT, but even in this current era of acyclovir or valacyclovir prophylaxis, infections occur at relatively high rates after auto-HCT, he noted.
“Now another approach to prevention of herpes zoster infection is vaccination,” he said.
The live attenuated vaccine currently on the market is generally contraindicated in immunocompromised patients – at least in early period after transplantation, but ZVIN showed promise with respect to safety in earlier studies, which led to the current trial.
“This study demonstrated that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr. Winston said, noting that efficacy was observed both in those younger than age 50 years and in those aged 50 and older, and also in those who received prophylaxis for less than 3 months and for 3-6 months.
“Finally!” said one audience member, who noted during a discussion of the findings that there has long been a need for a vaccine to prevent herpes zoster in auto-HCT patients.
Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.
ORLANDO – An inactivated varicella zoster virus vaccine currently in development for adult patients undergoing autologous hematopoietic stem cell transplantation is efficacious and well tolerated, according to findings from a randomized, placebo-controlled, phase III trial.
During the course of the 2 1/2-year pivotal multicenter trial, confirmed herpes zoster infections occurred in 42 of 560 patients who were randomized to receive inactivated varicella zoster virus vaccine (ZVIN) consistency lot (overall incidence of 32.8 cases/1,000 patient-years), compared with 113 of 564 patients who received placebo (overall incidence of 91.8/1,000 patient-years). The estimated vaccine efficacy was 63.8% after adjusting for age and duration of antiviral prophylaxis, Drew J. Winston, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
The vaccine also was effective for reducing moderate and severe herpes zoster pain (estimated vaccine efficacy, 69.5%), for preventing postherpetic neuralgia (estimated vaccine efficacy, 83.7%), and for prevention of herpes zoster–related complications (estimated vaccine efficacy, 73.5%), he noted.
Study subjects were adults aged 18 years or older who were undergoing autologous hematopoietic stem cell transplantation (auto-HCT) for a malignancy or other indication. The most common underlying diseases were lymphoma and multiple myeloma. All patients had a history of varicella infection or were seropositive for varicella zoster virus (VZV) antibody, and had no history of VZV vaccine or herpes zoster infection within the prior year.
They were randomized to receive a four-dose regimen of either ZVIN consistency lot, ZVIN high-antigen lot, or placebo. A group of 106 patients who received the ZVIN high-antigen lot were included in the safety analysis only. The first ZVIN dose was administered about a month before transplantation, and doses two through four were administered about 30, 60, and 90 days after transplantation. About 90% in each group received antiviral agents after transplantation, and the duration of the use of antivirals also was similar in the groups. All patients were followed for the duration of the study, and those who developed herpes zoster were followed for 6 months after onset.
Herpes zoster cases were confirmed by polymerase chain reaction or by blinded endpoint committee adjudication.
Serious adverse events and vaccine-related serious adverse events occurred in a similar proportion of patients in the treatment and placebo groups (32.9% and 32.7%, and 0.8% and 0.9%, respectively). Vaccine-related events were primarily injection-site reactions. Systemic adverse events that occurred up to 28 days after vaccination were mainly gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Pyrexia, oral mucositis, thrombocytopenia, and febrile neutropenia also were reported.
The most common serious adverse events were infectious complications, such as febrile neutropenia and relapse of underlying disease.
The findings are notable, as patients undergoing auto-HCT have an increased risk of developing herpes zoster infection and its complications, including postherpetic neuralgia, secondary bacterial infections, and disseminated VZV infection, as well as an increased risk of hospitalization and mortality, Dr. Winston explained.
Herpes zoster infections are associated primarily with cell-mediated immunity, and in older studies done prior to the routine use of antiviral prophylaxis, the reported incidence in auto-HCT patients was between 16% and 25%. Because of this high risk, current guidelines call for antiviral prophylaxis during auto-HCT, but even in this current era of acyclovir or valacyclovir prophylaxis, infections occur at relatively high rates after auto-HCT, he noted.
“Now another approach to prevention of herpes zoster infection is vaccination,” he said.
The live attenuated vaccine currently on the market is generally contraindicated in immunocompromised patients – at least in early period after transplantation, but ZVIN showed promise with respect to safety in earlier studies, which led to the current trial.
“This study demonstrated that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr. Winston said, noting that efficacy was observed both in those younger than age 50 years and in those aged 50 and older, and also in those who received prophylaxis for less than 3 months and for 3-6 months.
“Finally!” said one audience member, who noted during a discussion of the findings that there has long been a need for a vaccine to prevent herpes zoster in auto-HCT patients.
Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.
ORLANDO – An inactivated varicella zoster virus vaccine currently in development for adult patients undergoing autologous hematopoietic stem cell transplantation is efficacious and well tolerated, according to findings from a randomized, placebo-controlled, phase III trial.
During the course of the 2 1/2-year pivotal multicenter trial, confirmed herpes zoster infections occurred in 42 of 560 patients who were randomized to receive inactivated varicella zoster virus vaccine (ZVIN) consistency lot (overall incidence of 32.8 cases/1,000 patient-years), compared with 113 of 564 patients who received placebo (overall incidence of 91.8/1,000 patient-years). The estimated vaccine efficacy was 63.8% after adjusting for age and duration of antiviral prophylaxis, Drew J. Winston, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
The vaccine also was effective for reducing moderate and severe herpes zoster pain (estimated vaccine efficacy, 69.5%), for preventing postherpetic neuralgia (estimated vaccine efficacy, 83.7%), and for prevention of herpes zoster–related complications (estimated vaccine efficacy, 73.5%), he noted.
Study subjects were adults aged 18 years or older who were undergoing autologous hematopoietic stem cell transplantation (auto-HCT) for a malignancy or other indication. The most common underlying diseases were lymphoma and multiple myeloma. All patients had a history of varicella infection or were seropositive for varicella zoster virus (VZV) antibody, and had no history of VZV vaccine or herpes zoster infection within the prior year.
They were randomized to receive a four-dose regimen of either ZVIN consistency lot, ZVIN high-antigen lot, or placebo. A group of 106 patients who received the ZVIN high-antigen lot were included in the safety analysis only. The first ZVIN dose was administered about a month before transplantation, and doses two through four were administered about 30, 60, and 90 days after transplantation. About 90% in each group received antiviral agents after transplantation, and the duration of the use of antivirals also was similar in the groups. All patients were followed for the duration of the study, and those who developed herpes zoster were followed for 6 months after onset.
Herpes zoster cases were confirmed by polymerase chain reaction or by blinded endpoint committee adjudication.
Serious adverse events and vaccine-related serious adverse events occurred in a similar proportion of patients in the treatment and placebo groups (32.9% and 32.7%, and 0.8% and 0.9%, respectively). Vaccine-related events were primarily injection-site reactions. Systemic adverse events that occurred up to 28 days after vaccination were mainly gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Pyrexia, oral mucositis, thrombocytopenia, and febrile neutropenia also were reported.
The most common serious adverse events were infectious complications, such as febrile neutropenia and relapse of underlying disease.
The findings are notable, as patients undergoing auto-HCT have an increased risk of developing herpes zoster infection and its complications, including postherpetic neuralgia, secondary bacterial infections, and disseminated VZV infection, as well as an increased risk of hospitalization and mortality, Dr. Winston explained.
Herpes zoster infections are associated primarily with cell-mediated immunity, and in older studies done prior to the routine use of antiviral prophylaxis, the reported incidence in auto-HCT patients was between 16% and 25%. Because of this high risk, current guidelines call for antiviral prophylaxis during auto-HCT, but even in this current era of acyclovir or valacyclovir prophylaxis, infections occur at relatively high rates after auto-HCT, he noted.
“Now another approach to prevention of herpes zoster infection is vaccination,” he said.
The live attenuated vaccine currently on the market is generally contraindicated in immunocompromised patients – at least in early period after transplantation, but ZVIN showed promise with respect to safety in earlier studies, which led to the current trial.
“This study demonstrated that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr. Winston said, noting that efficacy was observed both in those younger than age 50 years and in those aged 50 and older, and also in those who received prophylaxis for less than 3 months and for 3-6 months.
“Finally!” said one audience member, who noted during a discussion of the findings that there has long been a need for a vaccine to prevent herpes zoster in auto-HCT patients.
Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.
AT THE 2017 BMT TANDEM MEETINGS
Key clinical point:
Major finding: Overall incidence of herpes zoster was 32.8 cases/1,000 patient-years vs. 91.8/1,000 patient-years in patients in the vaccine and placebo groups, respectively.
Data source: A randomized, placebo-controlled phase III trial involving 1,230 patients.
Disclosures: Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.
Neuropathic pain puts cancer survivors out of work
AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.
“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.
Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.
Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.
To assess CNP, the researchers used data from a seven-item questionnaire designed to identify neuropathic characteristics of pain experienced by patients in the 2 weeks prior to a comprehensive patient interview.
Of the 982 patients who were working at the time of diagnosis, 36% reported pain within the previous 2 weeks, and of this group, 79% had chronic pain of neuropathic origin. CNP was more common in women than in men (P less than .01); in college-educated people, compared with less-educated people (P less than .001); those who had undergone chemotherapy, compared with no chemotherapy (P less than .001); and those who had radiotherapy vs. no radiotherapy (P less than .001).
For each cancer site, the prevalence of CNP among 5-year cancer survivors was substantially higher than the overall prevalence in France of 7%. For example, 34% of patients with cancers of the cervix and endometrium reported CNP, as did 29.9% of patients who survived cancers of the lip, oral cavity, and pharynx, 32.1% of lung cancer survivors, and 32.7% of breast cancer survivors.
Five years after diagnosis, 22.6% of patients who had been employed in 2010 were out of work in 2015.
The presence of CNP was associated with a nearly twofold greater risk of unemployment (adjusted odds ratio, 1.96; P less than .001) in a multivariate logistic regression analysis comparing employed and unemployed patients and controlling for social and demographic characteristics, job characteristics at diagnosis, and medical factors such as tumor site, prognosis, and treatment type.
The French National Cancer Institute and INSERM, the National Institute for Research in Health and Medicine, supported the study. The investigators reported no conflicts of interest.
AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.
“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.
Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.
Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.
To assess CNP, the researchers used data from a seven-item questionnaire designed to identify neuropathic characteristics of pain experienced by patients in the 2 weeks prior to a comprehensive patient interview.
Of the 982 patients who were working at the time of diagnosis, 36% reported pain within the previous 2 weeks, and of this group, 79% had chronic pain of neuropathic origin. CNP was more common in women than in men (P less than .01); in college-educated people, compared with less-educated people (P less than .001); those who had undergone chemotherapy, compared with no chemotherapy (P less than .001); and those who had radiotherapy vs. no radiotherapy (P less than .001).
For each cancer site, the prevalence of CNP among 5-year cancer survivors was substantially higher than the overall prevalence in France of 7%. For example, 34% of patients with cancers of the cervix and endometrium reported CNP, as did 29.9% of patients who survived cancers of the lip, oral cavity, and pharynx, 32.1% of lung cancer survivors, and 32.7% of breast cancer survivors.
Five years after diagnosis, 22.6% of patients who had been employed in 2010 were out of work in 2015.
The presence of CNP was associated with a nearly twofold greater risk of unemployment (adjusted odds ratio, 1.96; P less than .001) in a multivariate logistic regression analysis comparing employed and unemployed patients and controlling for social and demographic characteristics, job characteristics at diagnosis, and medical factors such as tumor site, prognosis, and treatment type.
The French National Cancer Institute and INSERM, the National Institute for Research in Health and Medicine, supported the study. The investigators reported no conflicts of interest.
AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.
“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.
Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.
Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.
To assess CNP, the researchers used data from a seven-item questionnaire designed to identify neuropathic characteristics of pain experienced by patients in the 2 weeks prior to a comprehensive patient interview.
Of the 982 patients who were working at the time of diagnosis, 36% reported pain within the previous 2 weeks, and of this group, 79% had chronic pain of neuropathic origin. CNP was more common in women than in men (P less than .01); in college-educated people, compared with less-educated people (P less than .001); those who had undergone chemotherapy, compared with no chemotherapy (P less than .001); and those who had radiotherapy vs. no radiotherapy (P less than .001).
For each cancer site, the prevalence of CNP among 5-year cancer survivors was substantially higher than the overall prevalence in France of 7%. For example, 34% of patients with cancers of the cervix and endometrium reported CNP, as did 29.9% of patients who survived cancers of the lip, oral cavity, and pharynx, 32.1% of lung cancer survivors, and 32.7% of breast cancer survivors.
Five years after diagnosis, 22.6% of patients who had been employed in 2010 were out of work in 2015.
The presence of CNP was associated with a nearly twofold greater risk of unemployment (adjusted odds ratio, 1.96; P less than .001) in a multivariate logistic regression analysis comparing employed and unemployed patients and controlling for social and demographic characteristics, job characteristics at diagnosis, and medical factors such as tumor site, prognosis, and treatment type.
The French National Cancer Institute and INSERM, the National Institute for Research in Health and Medicine, supported the study. The investigators reported no conflicts of interest.
Key clinical point: Chronic neuropathic pain is a barrier to employment for many cancer survivors.
Major finding: Cancer survivors with chronic neuropathic pain were twice as likely to be unemployed 5 years after diagnosis as patients with no pain.
Data source: Longitudinal study of French cancer survivors.
Disclosures: The French National Cancer Institute and INSERM, the National Institute for Research in Health and Medicine, supported the study. The investigators reported no conflicts of interest.