T Cell Lymphomas

The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

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.

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The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

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.

[email protected]

The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

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.

[email protected]

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.

copyright varaphoto/Thinkstock

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.

copyright varaphoto/Thinkstock

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.

copyright varaphoto/Thinkstock

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 (ZV_IN) 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 ZV_IN consistency lot, ZV_IN high-antigen lot, or placebo. A group of 106 patients who received the ZV_IN high-antigen lot were included in the safety analysis only. The first ZV_IN 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 ZV_IN 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.

[email protected]

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 (ZV_IN) 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 ZV_IN consistency lot, ZV_IN high-antigen lot, or placebo. A group of 106 patients who received the ZV_IN high-antigen lot were included in the safety analysis only. The first ZV_IN 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 ZV_IN 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.

[email protected]

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 (ZV_IN) 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 ZV_IN consistency lot, ZV_IN high-antigen lot, or placebo. A group of 106 patients who received the ZV_IN high-antigen lot were included in the safety analysis only. The first ZV_IN 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 ZV_IN 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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

SAN DIEGO – For patients with CD30 expressing cutaneous T-cell lymphoma, antibody-drug conjugate therapy with brentuximab vedotin significantly outperformed two standard regimens in the phase III ALCANZA trial.

After a median of 17.5 months of follow-up, 56% of patients receiving brentuximab vedotin had an objective response lasting at least 4 months, versus 13% of patients treated with physician’s choice of methotrexate or bexarotene (P less than .0001), Youn H. Kim, MD, said during an oral presentation at the annual meeting of the American Society of Hematology.

As in past studies, brentuximab vedotin caused high rates of peripheral neuropathy, but more than 80% of cases improved or resolved over time, she said.

This is the first reported phase III trial to convincingly show that a new systemic agent outperformed standard therapies for cutaneous T-cell lymphoma (CTCL), which tend to have inadequate and short-lived efficacy, stated Dr. Kim, of Stanford (Calif.) University. Brentuximab vedotin not only met the primary endpoint, but all other predefined endpoints, including progression-free survival and a quality-of-life measure, she said.

“These compelling results have potential practice-changing implications,” she concluded.

Brentuximab vedotin (Adcetris) targets CD30, which is expressed in skin lesions of about half of patients with CTCL. A protease-cleavable linker attaches an anti-CD30 monoclonal antibody to monomethyl auristatin E, which disrupts microtubules when released into CD30-positive tumor cells (Blood. 2013;122:367). The agent showed clinical activity against CTCL in two previous phase II trials of CTCL.

Accordingly, the international, open-label phase III ALCANZA study enrolled 128 treatment-experienced patients with CD30-expressing mycosis fungoides or primary cutaneous anaplastic large cell lymphoma. Patients were randomly assigned to receive brentuximab vedotin (1.8 mg/kg once every 3 weeks) or physician’s choice of either methotrexate (5 to 50 mg once weekly) or bexarotene (300 mg/m² once daily) for up to 16 3-week cycles, or until disease progression or unacceptable toxicity. Methotrexate or bexarotene were designated “physician’s choice” because they are used worldwide for treating CTCL, according to Dr. Kim.

To capture both the rate and duration of response, researchers defined objective response lasting at least 4 months as the primary endpoint. Brentuximab vedotin more than quadrupled the likelihood of this outcome when compared with the standard CTCL regimens, a trend that spanned key demographic and clinical subgroups, Dr. Kim said.

“All endpoints were highly [statistically] significant,” she further reported. For example, the objective response rate with brentuximab vedotin was 67%, versus 20% for methotrexate or bexarotene. Respective rates of complete response were 16% and 2%, and median durations of progression-free survival were 17 and 4 months, translating to a 73% lower risk of progression or death with brentuximab vedotin (95% confidence interval, 57%-83%). Patients who received brentuximab vedotin also reported about a three-fold greater improvement on the Skindex-29 symptom domain, compared with the physician’s choice group (–29 vs. –9 points; P less than .0001).

The safety profile of brentuximab vedotin resembled that seen in previous studies, Dr. Kim said. Most notably, 67% of patients developed peripheral neuropathy, and 9% developed grade 3 peripheral neuropathy. This usually improved or resolved over about the next 22 months. Diarrhea, fatigue, and vomiting affected about a third of patients on brentuximab vedotin, and about one in four stopped treatment because of adverse events, compared with 8% of the physician’s choice arm. Rates of serious adverse events were 41% and 47%, respectively. One brentuximab vedotin recipient died of multiple organ dysfunction syndrome that investigators attributed to treatment-associated necrosis of peripheral tumors. They identified no other treatment-related deaths.

Seattle Genetics and Takeda funded the trial. Dr. Kim disclosed ties to Takeda and Seattle Genetics, as well as several other pharmaceutical companies.

SAN DIEGO – For patients with CD30 expressing cutaneous T-cell lymphoma, antibody-drug conjugate therapy with brentuximab vedotin significantly outperformed two standard regimens in the phase III ALCANZA trial.

After a median of 17.5 months of follow-up, 56% of patients receiving brentuximab vedotin had an objective response lasting at least 4 months, versus 13% of patients treated with physician’s choice of methotrexate or bexarotene (P less than .0001), Youn H. Kim, MD, said during an oral presentation at the annual meeting of the American Society of Hematology.

As in past studies, brentuximab vedotin caused high rates of peripheral neuropathy, but more than 80% of cases improved or resolved over time, she said.

This is the first reported phase III trial to convincingly show that a new systemic agent outperformed standard therapies for cutaneous T-cell lymphoma (CTCL), which tend to have inadequate and short-lived efficacy, stated Dr. Kim, of Stanford (Calif.) University. Brentuximab vedotin not only met the primary endpoint, but all other predefined endpoints, including progression-free survival and a quality-of-life measure, she said.

“These compelling results have potential practice-changing implications,” she concluded.

Brentuximab vedotin (Adcetris) targets CD30, which is expressed in skin lesions of about half of patients with CTCL. A protease-cleavable linker attaches an anti-CD30 monoclonal antibody to monomethyl auristatin E, which disrupts microtubules when released into CD30-positive tumor cells (Blood. 2013;122:367). The agent showed clinical activity against CTCL in two previous phase II trials of CTCL.

Accordingly, the international, open-label phase III ALCANZA study enrolled 128 treatment-experienced patients with CD30-expressing mycosis fungoides or primary cutaneous anaplastic large cell lymphoma. Patients were randomly assigned to receive brentuximab vedotin (1.8 mg/kg once every 3 weeks) or physician’s choice of either methotrexate (5 to 50 mg once weekly) or bexarotene (300 mg/m² once daily) for up to 16 3-week cycles, or until disease progression or unacceptable toxicity. Methotrexate or bexarotene were designated “physician’s choice” because they are used worldwide for treating CTCL, according to Dr. Kim.

To capture both the rate and duration of response, researchers defined objective response lasting at least 4 months as the primary endpoint. Brentuximab vedotin more than quadrupled the likelihood of this outcome when compared with the standard CTCL regimens, a trend that spanned key demographic and clinical subgroups, Dr. Kim said.

“All endpoints were highly [statistically] significant,” she further reported. For example, the objective response rate with brentuximab vedotin was 67%, versus 20% for methotrexate or bexarotene. Respective rates of complete response were 16% and 2%, and median durations of progression-free survival were 17 and 4 months, translating to a 73% lower risk of progression or death with brentuximab vedotin (95% confidence interval, 57%-83%). Patients who received brentuximab vedotin also reported about a three-fold greater improvement on the Skindex-29 symptom domain, compared with the physician’s choice group (–29 vs. –9 points; P less than .0001).

The safety profile of brentuximab vedotin resembled that seen in previous studies, Dr. Kim said. Most notably, 67% of patients developed peripheral neuropathy, and 9% developed grade 3 peripheral neuropathy. This usually improved or resolved over about the next 22 months. Diarrhea, fatigue, and vomiting affected about a third of patients on brentuximab vedotin, and about one in four stopped treatment because of adverse events, compared with 8% of the physician’s choice arm. Rates of serious adverse events were 41% and 47%, respectively. One brentuximab vedotin recipient died of multiple organ dysfunction syndrome that investigators attributed to treatment-associated necrosis of peripheral tumors. They identified no other treatment-related deaths.

Seattle Genetics and Takeda funded the trial. Dr. Kim disclosed ties to Takeda and Seattle Genetics, as well as several other pharmaceutical companies.

SAN DIEGO – For patients with CD30 expressing cutaneous T-cell lymphoma, antibody-drug conjugate therapy with brentuximab vedotin significantly outperformed two standard regimens in the phase III ALCANZA trial.

After a median of 17.5 months of follow-up, 56% of patients receiving brentuximab vedotin had an objective response lasting at least 4 months, versus 13% of patients treated with physician’s choice of methotrexate or bexarotene (P less than .0001), Youn H. Kim, MD, said during an oral presentation at the annual meeting of the American Society of Hematology.

As in past studies, brentuximab vedotin caused high rates of peripheral neuropathy, but more than 80% of cases improved or resolved over time, she said.

This is the first reported phase III trial to convincingly show that a new systemic agent outperformed standard therapies for cutaneous T-cell lymphoma (CTCL), which tend to have inadequate and short-lived efficacy, stated Dr. Kim, of Stanford (Calif.) University. Brentuximab vedotin not only met the primary endpoint, but all other predefined endpoints, including progression-free survival and a quality-of-life measure, she said.

“These compelling results have potential practice-changing implications,” she concluded.

Brentuximab vedotin (Adcetris) targets CD30, which is expressed in skin lesions of about half of patients with CTCL. A protease-cleavable linker attaches an anti-CD30 monoclonal antibody to monomethyl auristatin E, which disrupts microtubules when released into CD30-positive tumor cells (Blood. 2013;122:367). The agent showed clinical activity against CTCL in two previous phase II trials of CTCL.

Accordingly, the international, open-label phase III ALCANZA study enrolled 128 treatment-experienced patients with CD30-expressing mycosis fungoides or primary cutaneous anaplastic large cell lymphoma. Patients were randomly assigned to receive brentuximab vedotin (1.8 mg/kg once every 3 weeks) or physician’s choice of either methotrexate (5 to 50 mg once weekly) or bexarotene (300 mg/m² once daily) for up to 16 3-week cycles, or until disease progression or unacceptable toxicity. Methotrexate or bexarotene were designated “physician’s choice” because they are used worldwide for treating CTCL, according to Dr. Kim.

To capture both the rate and duration of response, researchers defined objective response lasting at least 4 months as the primary endpoint. Brentuximab vedotin more than quadrupled the likelihood of this outcome when compared with the standard CTCL regimens, a trend that spanned key demographic and clinical subgroups, Dr. Kim said.

“All endpoints were highly [statistically] significant,” she further reported. For example, the objective response rate with brentuximab vedotin was 67%, versus 20% for methotrexate or bexarotene. Respective rates of complete response were 16% and 2%, and median durations of progression-free survival were 17 and 4 months, translating to a 73% lower risk of progression or death with brentuximab vedotin (95% confidence interval, 57%-83%). Patients who received brentuximab vedotin also reported about a three-fold greater improvement on the Skindex-29 symptom domain, compared with the physician’s choice group (–29 vs. –9 points; P less than .0001).

The safety profile of brentuximab vedotin resembled that seen in previous studies, Dr. Kim said. Most notably, 67% of patients developed peripheral neuropathy, and 9% developed grade 3 peripheral neuropathy. This usually improved or resolved over about the next 22 months. Diarrhea, fatigue, and vomiting affected about a third of patients on brentuximab vedotin, and about one in four stopped treatment because of adverse events, compared with 8% of the physician’s choice arm. Rates of serious adverse events were 41% and 47%, respectively. One brentuximab vedotin recipient died of multiple organ dysfunction syndrome that investigators attributed to treatment-associated necrosis of peripheral tumors. They identified no other treatment-related deaths.

Seattle Genetics and Takeda funded the trial. Dr. Kim disclosed ties to Takeda and Seattle Genetics, as well as several other pharmaceutical companies.

Lenalidomide monotherapy demonstrated “meaningful” antitumor activity in patients with relapsed or recurrent aggressive adult T-cell leukemia/lymphoma (ATL), according to new findings.

Among 26 patients enrolled in the study, 11 responses were observed, for an overall response rate of 42% (95% CI, 23%-63%). This included four complete responses and one unconfirmed complete response.

The tumor control rate was 73%, achieved in 19 patients, and the toxicity profile was manageable. Overall, these findings hint at the potential of lenalidomide to “become a treatment option in this patient population,” wrote Takashi Ishida, MD, of Nagoya City University Graduate School of Medical Sciences, Aichi, Japan, and his colleagues (J Clin Oncol. 2016 Sep 12. doi: 10.1200/JCO.2016.67.7732).

ATL is a difficult disease to treat, and it has a poor prognosis, as it is resistant to conventional chemotherapeutic agents and treatment options are currently limited. Lenalidomide, an oral immunomodulatory agent, has demonstrated both antiproliferative and antineoplastic activity in B-cell lymphomas in preclinical studies, and a previous phase I trial established a maximum tolerated dosage (25 mg/d) in a small cohort of Japanese patients with relapsed ATL or other peripheral T-cell lymphomas (PTCL).

Based on these preliminary results, Dr. Ishida and his coauthors designed the current multicenter phase II study, to evaluate the efficacy and safety of lenalidomide monotherapy in 26 patients with relapsed or recurrent ATL.­­­

At a median follow-up of 3.9 months, responses were observed in 33% of patients (5 of 15) with acute disease, 57% (4 of 7) with lymphoma, and 50% (2 of 4) for unfavorable chronic ATL. Patient responses according to disease site were 31% for target (nodal and extranodal) lesions, 75% for cutaneous lesions, and 60% for peripheral blood. 

The median time to relapse was 1.9 months (range, 1.8-3.7 months), while the median time to progression was 3.8 months (95% CI, 1.9 to not estimable [NE]). The median and mean duration of response for the entire cohort were NE (95% CI, 0.5 months to NE) and 5.2 months (range, 0 to 16.6 months), respectively.

Progression-free survival was 3.8 months (95% CI, 1.9 months to NE) and for overall survival, it was 20.3 months (95% CI, 9.1 months to NE).

Adverse events occurred in more than 20% of patients and the most common hematologic event was thrombocytopenia (77%). The most common nonhematologic event was increased C-reactive protein (42%), and hypoalbuminemia and hypoproteinemia were observed in about a third of patients, as were constipation, hyponatremia, and hypocalcemia (all 31%).

Dr. Ishida and several coauthors reported multiple relationships with industry, including Celgene K.K. (Tokyo), the study’s sponsor.

Lenalidomide monotherapy demonstrated “meaningful” antitumor activity in patients with relapsed or recurrent aggressive adult T-cell leukemia/lymphoma (ATL), according to new findings.

Among 26 patients enrolled in the study, 11 responses were observed, for an overall response rate of 42% (95% CI, 23%-63%). This included four complete responses and one unconfirmed complete response.

The tumor control rate was 73%, achieved in 19 patients, and the toxicity profile was manageable. Overall, these findings hint at the potential of lenalidomide to “become a treatment option in this patient population,” wrote Takashi Ishida, MD, of Nagoya City University Graduate School of Medical Sciences, Aichi, Japan, and his colleagues (J Clin Oncol. 2016 Sep 12. doi: 10.1200/JCO.2016.67.7732).

ATL is a difficult disease to treat, and it has a poor prognosis, as it is resistant to conventional chemotherapeutic agents and treatment options are currently limited. Lenalidomide, an oral immunomodulatory agent, has demonstrated both antiproliferative and antineoplastic activity in B-cell lymphomas in preclinical studies, and a previous phase I trial established a maximum tolerated dosage (25 mg/d) in a small cohort of Japanese patients with relapsed ATL or other peripheral T-cell lymphomas (PTCL).

Based on these preliminary results, Dr. Ishida and his coauthors designed the current multicenter phase II study, to evaluate the efficacy and safety of lenalidomide monotherapy in 26 patients with relapsed or recurrent ATL.­­­

At a median follow-up of 3.9 months, responses were observed in 33% of patients (5 of 15) with acute disease, 57% (4 of 7) with lymphoma, and 50% (2 of 4) for unfavorable chronic ATL. Patient responses according to disease site were 31% for target (nodal and extranodal) lesions, 75% for cutaneous lesions, and 60% for peripheral blood. 

The median time to relapse was 1.9 months (range, 1.8-3.7 months), while the median time to progression was 3.8 months (95% CI, 1.9 to not estimable [NE]). The median and mean duration of response for the entire cohort were NE (95% CI, 0.5 months to NE) and 5.2 months (range, 0 to 16.6 months), respectively.

Progression-free survival was 3.8 months (95% CI, 1.9 months to NE) and for overall survival, it was 20.3 months (95% CI, 9.1 months to NE).

Adverse events occurred in more than 20% of patients and the most common hematologic event was thrombocytopenia (77%). The most common nonhematologic event was increased C-reactive protein (42%), and hypoalbuminemia and hypoproteinemia were observed in about a third of patients, as were constipation, hyponatremia, and hypocalcemia (all 31%).

Dr. Ishida and several coauthors reported multiple relationships with industry, including Celgene K.K. (Tokyo), the study’s sponsor.

Lenalidomide monotherapy demonstrated “meaningful” antitumor activity in patients with relapsed or recurrent aggressive adult T-cell leukemia/lymphoma (ATL), according to new findings.

Among 26 patients enrolled in the study, 11 responses were observed, for an overall response rate of 42% (95% CI, 23%-63%). This included four complete responses and one unconfirmed complete response.

The tumor control rate was 73%, achieved in 19 patients, and the toxicity profile was manageable. Overall, these findings hint at the potential of lenalidomide to “become a treatment option in this patient population,” wrote Takashi Ishida, MD, of Nagoya City University Graduate School of Medical Sciences, Aichi, Japan, and his colleagues (J Clin Oncol. 2016 Sep 12. doi: 10.1200/JCO.2016.67.7732).

ATL is a difficult disease to treat, and it has a poor prognosis, as it is resistant to conventional chemotherapeutic agents and treatment options are currently limited. Lenalidomide, an oral immunomodulatory agent, has demonstrated both antiproliferative and antineoplastic activity in B-cell lymphomas in preclinical studies, and a previous phase I trial established a maximum tolerated dosage (25 mg/d) in a small cohort of Japanese patients with relapsed ATL or other peripheral T-cell lymphomas (PTCL).

Based on these preliminary results, Dr. Ishida and his coauthors designed the current multicenter phase II study, to evaluate the efficacy and safety of lenalidomide monotherapy in 26 patients with relapsed or recurrent ATL.­­­

At a median follow-up of 3.9 months, responses were observed in 33% of patients (5 of 15) with acute disease, 57% (4 of 7) with lymphoma, and 50% (2 of 4) for unfavorable chronic ATL. Patient responses according to disease site were 31% for target (nodal and extranodal) lesions, 75% for cutaneous lesions, and 60% for peripheral blood. 

The median time to relapse was 1.9 months (range, 1.8-3.7 months), while the median time to progression was 3.8 months (95% CI, 1.9 to not estimable [NE]). The median and mean duration of response for the entire cohort were NE (95% CI, 0.5 months to NE) and 5.2 months (range, 0 to 16.6 months), respectively.

Progression-free survival was 3.8 months (95% CI, 1.9 months to NE) and for overall survival, it was 20.3 months (95% CI, 9.1 months to NE).

Adverse events occurred in more than 20% of patients and the most common hematologic event was thrombocytopenia (77%). The most common nonhematologic event was increased C-reactive protein (42%), and hypoalbuminemia and hypoproteinemia were observed in about a third of patients, as were constipation, hyponatremia, and hypocalcemia (all 31%).

Dr. Ishida and several coauthors reported multiple relationships with industry, including Celgene K.K. (Tokyo), the study’s sponsor.

The use of mogamulizumab before allogeneic hematopoietic stem-cell transplantation in aggressive adult T-cell leukemia/lymphoma is associated with an increased risk of acute graft-versus-host disease (GVHD), which leads to an inferior overall survival, investigators report in the Journal of Clinical Oncology.

Mogamulizumab is an anti-CCR4 monoclonal antibody that showed promise in small clinical studies when added to conventional chemotherapy as first-line treatment. It was recently approved for the treatment of adult T-cell leukemia/lymphoma in Japan, and eventually may be approved in the U.S. and other countries, said Shigeo Fuji, MD, of the department of hematopoietic stem-cell transplantation, National Cancer Center Hospital, Tokyo, and his associates.

The agent significantly depleted regulatory T cells for several months in animal models. This prompted concern regarding the possibility of exacerbating GVHD in human patients who don’t respond completely to first-line chemotherapy and then undergo stem-cell transplantation. “However, no direct evidence has demonstrated [regulatory T-cell] depletion in humans,” the investigators noted.

To examine this issue, they assessed clinical outcomes in a cohort of 996 patients across Japan who had aggressive adult T-cell leukemia/lymphoma, were aged 20-69 years, were diagnosed in 2000-2013, and received intensive, multiagent chemotherapy before undergoing allogeneic hematopoietic stem-cell transplantation.

Grade 2-4 acute GVHD developed in 381 of 873 patients who didn’t receive mogamulizumab (43.6%), compared with 47 of 81 patients who did receive the agent (58.0%), for a relative risk of 1.33 (P = .01). Grade 3-4 acute GVHD developed in 150 patients who didn’t receive mogamulizumab (17.2%), compared with 25 who did (30.9%), for an RR of 1.80 (P less than .01) .

The agent not only raised the rate of GVHD, it also increased the severity of the disorder. GVHD was refractory to systemic corticosteroids in 23.5% of patients who didn’t receive mogamulizumab, compared with 48.9% of those who did, for an RR of 2.09 (P less than .01), the investigators reported (J Clin Oncol. 2016. doi: 10.1200/JCO.2016.67.8250).

In addition, 1-year disease-free mortality was 25.1% without mogamulizumab, compared with 43.7% with it. The estimated 1-year overall survival was 49.4% without mogamulizumab, compared with 32.3% with it. And in multivariable analyses, receiving mogamulizumab before undergoing stem-cell transplantation was a significant risk factor for both disease-free mortality (hazard ratio, 1.93) and overall mortality (HR, 1.67).

“All hematologists should take the risks and benefits of mogamulizumab into consideration before they use [it] in transplantation-eligible patients,” Dr. Fuji and his associates said.

The use of mogamulizumab before allogeneic hematopoietic stem-cell transplantation in aggressive adult T-cell leukemia/lymphoma is associated with an increased risk of acute graft-versus-host disease (GVHD), which leads to an inferior overall survival, investigators report in the Journal of Clinical Oncology.

Mogamulizumab is an anti-CCR4 monoclonal antibody that showed promise in small clinical studies when added to conventional chemotherapy as first-line treatment. It was recently approved for the treatment of adult T-cell leukemia/lymphoma in Japan, and eventually may be approved in the U.S. and other countries, said Shigeo Fuji, MD, of the department of hematopoietic stem-cell transplantation, National Cancer Center Hospital, Tokyo, and his associates.

The agent significantly depleted regulatory T cells for several months in animal models. This prompted concern regarding the possibility of exacerbating GVHD in human patients who don’t respond completely to first-line chemotherapy and then undergo stem-cell transplantation. “However, no direct evidence has demonstrated [regulatory T-cell] depletion in humans,” the investigators noted.

To examine this issue, they assessed clinical outcomes in a cohort of 996 patients across Japan who had aggressive adult T-cell leukemia/lymphoma, were aged 20-69 years, were diagnosed in 2000-2013, and received intensive, multiagent chemotherapy before undergoing allogeneic hematopoietic stem-cell transplantation.

Grade 2-4 acute GVHD developed in 381 of 873 patients who didn’t receive mogamulizumab (43.6%), compared with 47 of 81 patients who did receive the agent (58.0%), for a relative risk of 1.33 (P = .01). Grade 3-4 acute GVHD developed in 150 patients who didn’t receive mogamulizumab (17.2%), compared with 25 who did (30.9%), for an RR of 1.80 (P less than .01) .

The agent not only raised the rate of GVHD, it also increased the severity of the disorder. GVHD was refractory to systemic corticosteroids in 23.5% of patients who didn’t receive mogamulizumab, compared with 48.9% of those who did, for an RR of 2.09 (P less than .01), the investigators reported (J Clin Oncol. 2016. doi: 10.1200/JCO.2016.67.8250).

In addition, 1-year disease-free mortality was 25.1% without mogamulizumab, compared with 43.7% with it. The estimated 1-year overall survival was 49.4% without mogamulizumab, compared with 32.3% with it. And in multivariable analyses, receiving mogamulizumab before undergoing stem-cell transplantation was a significant risk factor for both disease-free mortality (hazard ratio, 1.93) and overall mortality (HR, 1.67).

“All hematologists should take the risks and benefits of mogamulizumab into consideration before they use [it] in transplantation-eligible patients,” Dr. Fuji and his associates said.

The use of mogamulizumab before allogeneic hematopoietic stem-cell transplantation in aggressive adult T-cell leukemia/lymphoma is associated with an increased risk of acute graft-versus-host disease (GVHD), which leads to an inferior overall survival, investigators report in the Journal of Clinical Oncology.

Mogamulizumab is an anti-CCR4 monoclonal antibody that showed promise in small clinical studies when added to conventional chemotherapy as first-line treatment. It was recently approved for the treatment of adult T-cell leukemia/lymphoma in Japan, and eventually may be approved in the U.S. and other countries, said Shigeo Fuji, MD, of the department of hematopoietic stem-cell transplantation, National Cancer Center Hospital, Tokyo, and his associates.

The agent significantly depleted regulatory T cells for several months in animal models. This prompted concern regarding the possibility of exacerbating GVHD in human patients who don’t respond completely to first-line chemotherapy and then undergo stem-cell transplantation. “However, no direct evidence has demonstrated [regulatory T-cell] depletion in humans,” the investigators noted.

To examine this issue, they assessed clinical outcomes in a cohort of 996 patients across Japan who had aggressive adult T-cell leukemia/lymphoma, were aged 20-69 years, were diagnosed in 2000-2013, and received intensive, multiagent chemotherapy before undergoing allogeneic hematopoietic stem-cell transplantation.

Grade 2-4 acute GVHD developed in 381 of 873 patients who didn’t receive mogamulizumab (43.6%), compared with 47 of 81 patients who did receive the agent (58.0%), for a relative risk of 1.33 (P = .01). Grade 3-4 acute GVHD developed in 150 patients who didn’t receive mogamulizumab (17.2%), compared with 25 who did (30.9%), for an RR of 1.80 (P less than .01) .

The agent not only raised the rate of GVHD, it also increased the severity of the disorder. GVHD was refractory to systemic corticosteroids in 23.5% of patients who didn’t receive mogamulizumab, compared with 48.9% of those who did, for an RR of 2.09 (P less than .01), the investigators reported (J Clin Oncol. 2016. doi: 10.1200/JCO.2016.67.8250).

In addition, 1-year disease-free mortality was 25.1% without mogamulizumab, compared with 43.7% with it. The estimated 1-year overall survival was 49.4% without mogamulizumab, compared with 32.3% with it. And in multivariable analyses, receiving mogamulizumab before undergoing stem-cell transplantation was a significant risk factor for both disease-free mortality (hazard ratio, 1.93) and overall mortality (HR, 1.67).

“All hematologists should take the risks and benefits of mogamulizumab into consideration before they use [it] in transplantation-eligible patients,” Dr. Fuji and his associates said.

SCOTTSDALE, ARIZ. – Psoriasis of all severities was linked to a 3.5-fold increase in risk of cutaneous T-cell lymphoma, and severe psoriasis upped the associated risk of Hodgkin lymphoma by about 2.5 times, in a large, longitudinal, population-based cohort study.

Psoriasis also was tied to a smaller but statistically significant increase in the risk of non-Hodgkin lymphoma, said Zelma Chiesa Fuxench, MD, of the department of dermatology, the University of Pennsylvania, Philadelphia. Overall, lymphoma risk was highest in people with severe psoriasis, independent of traditional risk factors and exposure to immunosuppressive medications, Dr. Fuxench said at the annual meeting of the Society for Investigative Dermatology.

Courtesy of the Centers for Disease Control and Prevention (CDC)

Psoriasis affects more than 125 million people worldwide, and severe cases are a major cause of cancer-related mortality. “Prior studies have suggested an increased risk of lymphoma in psoriasis patients, but it is unclear if this due to chronic inflammation, exposure to immunosuppressive therapies, or a combination of both factors,” Dr. Fuxench said.

To further explore these links, she and her associates analyzed electronic medical records from THIN (The Health Information Network), which includes about 12 million patients across the United Kingdom. Adults with psoriasis were matched to up to five nonpsoriatic controls based on date and clinic location. Patients who needed systemic medications or phototherapy were categorized as having severe psoriasis. The final dataset included more than 12,000 such patients, as well as 184,000 patients with mild psoriasis and more than 965,000 patients without psoriasis.

Psoriasis patients were younger and more likely to be overweight, male, and smoke and drink alcohol than patients without psoriasis, Dr. Fuxench said. Almost 80% of patients with severe disease had received systemic therapies, most often methotrexate (70% of systemic treatments) or cyclosporine (10%), while only 1% had received biologics.

Patients with severe psoriasis were more likely to be diagnosed with Hodgkin disease, non-Hodgkin lymphoma, and cutaneous T-cell lymphoma than were patients with mild psoriasis or controls. Over a median follow-up of 5.3 years, 34 patients with severe psoriasis were diagnosed with any type of lymphoma, for an incidence of 5.2 cases per 10,000 person-years (95% confidence interval, 3.7-7.3). In contrast, incidence rates for patients with mild psoriasis and controls were 3.3 and 3.2 cases per 10,000 person-years, respectively, Dr. Fuxench said.

In the multivariable analysis, patients with psoriasis were about 18% more likely to develop any type of lymphoma than were controls, an association that reached statistical significance (adjusted hazard ratio, 1.18; 95% CI, 1.06-1.31). Mild psoriasis increased lymphoma risk by 14%, and severe psoriasis upped it by about 83%, and both associations were statistically significant.

The increase in risk of non-Hodgkin lymphoma was 13% greater with mild psoriasis and 56% greater with severe disease, compared with controls, and these associations also reached statistical significance. Mild psoriasis was not linked to Hodgkin lymphoma, but patients with severe psoriasis were about 250% more likely to develop it than controls, with a trend toward statistical significance (aHR, 2.54; 95% CI, 0.94-6.87).

Finally, severe psoriasis was linked to a more than ninefold increase in risk of cutaneous T-cell lymphoma (aHR, 9.3; 95% CI, 4.1-21.4), while mild psoriasis was linked to about a threefold increase in risk.

“These results were robust in multiple sensitivity analyses, including analyses that excluded patients with rheumatoid arthritis, psoriatic arthritis, or a history of exposure to methotrexate, cyclosporine, or biologics,” Dr. Fuxench said. Future studies should explore the effect of treatment timing and selection on cancer risk, she added. “For those of us who care for these patients, we are increasingly using systemic agents that selectively target the immune system, and these questions will arise in clinics.”

The study’s design made it possible to pinpoint dates of diagnosis more effectively than investigators could estimate disease duration or confirm whether patients initially diagnosed with psoriasis actually had cutaneous T-cell lymphoma, Dr. Fuxench noted. “Ideally, we could have another cohort study of incident psoriasis with prospective follow-up, but lymphoma is so rare that there is currently not enough power [in the THIN database] to determine associations.”

The study was funded by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Fuxench disclosed unrestricted research funding from Pfizer outside the submitted work.

SCOTTSDALE, ARIZ. – Psoriasis of all severities was linked to a 3.5-fold increase in risk of cutaneous T-cell lymphoma, and severe psoriasis upped the associated risk of Hodgkin lymphoma by about 2.5 times, in a large, longitudinal, population-based cohort study.

Psoriasis also was tied to a smaller but statistically significant increase in the risk of non-Hodgkin lymphoma, said Zelma Chiesa Fuxench, MD, of the department of dermatology, the University of Pennsylvania, Philadelphia. Overall, lymphoma risk was highest in people with severe psoriasis, independent of traditional risk factors and exposure to immunosuppressive medications, Dr. Fuxench said at the annual meeting of the Society for Investigative Dermatology.

Courtesy of the Centers for Disease Control and Prevention (CDC)

Psoriasis affects more than 125 million people worldwide, and severe cases are a major cause of cancer-related mortality. “Prior studies have suggested an increased risk of lymphoma in psoriasis patients, but it is unclear if this due to chronic inflammation, exposure to immunosuppressive therapies, or a combination of both factors,” Dr. Fuxench said.

To further explore these links, she and her associates analyzed electronic medical records from THIN (The Health Information Network), which includes about 12 million patients across the United Kingdom. Adults with psoriasis were matched to up to five nonpsoriatic controls based on date and clinic location. Patients who needed systemic medications or phototherapy were categorized as having severe psoriasis. The final dataset included more than 12,000 such patients, as well as 184,000 patients with mild psoriasis and more than 965,000 patients without psoriasis.

Psoriasis patients were younger and more likely to be overweight, male, and smoke and drink alcohol than patients without psoriasis, Dr. Fuxench said. Almost 80% of patients with severe disease had received systemic therapies, most often methotrexate (70% of systemic treatments) or cyclosporine (10%), while only 1% had received biologics.

Patients with severe psoriasis were more likely to be diagnosed with Hodgkin disease, non-Hodgkin lymphoma, and cutaneous T-cell lymphoma than were patients with mild psoriasis or controls. Over a median follow-up of 5.3 years, 34 patients with severe psoriasis were diagnosed with any type of lymphoma, for an incidence of 5.2 cases per 10,000 person-years (95% confidence interval, 3.7-7.3). In contrast, incidence rates for patients with mild psoriasis and controls were 3.3 and 3.2 cases per 10,000 person-years, respectively, Dr. Fuxench said.

In the multivariable analysis, patients with psoriasis were about 18% more likely to develop any type of lymphoma than were controls, an association that reached statistical significance (adjusted hazard ratio, 1.18; 95% CI, 1.06-1.31). Mild psoriasis increased lymphoma risk by 14%, and severe psoriasis upped it by about 83%, and both associations were statistically significant.

The increase in risk of non-Hodgkin lymphoma was 13% greater with mild psoriasis and 56% greater with severe disease, compared with controls, and these associations also reached statistical significance. Mild psoriasis was not linked to Hodgkin lymphoma, but patients with severe psoriasis were about 250% more likely to develop it than controls, with a trend toward statistical significance (aHR, 2.54; 95% CI, 0.94-6.87).

Finally, severe psoriasis was linked to a more than ninefold increase in risk of cutaneous T-cell lymphoma (aHR, 9.3; 95% CI, 4.1-21.4), while mild psoriasis was linked to about a threefold increase in risk.

“These results were robust in multiple sensitivity analyses, including analyses that excluded patients with rheumatoid arthritis, psoriatic arthritis, or a history of exposure to methotrexate, cyclosporine, or biologics,” Dr. Fuxench said. Future studies should explore the effect of treatment timing and selection on cancer risk, she added. “For those of us who care for these patients, we are increasingly using systemic agents that selectively target the immune system, and these questions will arise in clinics.”

The study’s design made it possible to pinpoint dates of diagnosis more effectively than investigators could estimate disease duration or confirm whether patients initially diagnosed with psoriasis actually had cutaneous T-cell lymphoma, Dr. Fuxench noted. “Ideally, we could have another cohort study of incident psoriasis with prospective follow-up, but lymphoma is so rare that there is currently not enough power [in the THIN database] to determine associations.”

The study was funded by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Fuxench disclosed unrestricted research funding from Pfizer outside the submitted work.

SCOTTSDALE, ARIZ. – Psoriasis of all severities was linked to a 3.5-fold increase in risk of cutaneous T-cell lymphoma, and severe psoriasis upped the associated risk of Hodgkin lymphoma by about 2.5 times, in a large, longitudinal, population-based cohort study.

Psoriasis also was tied to a smaller but statistically significant increase in the risk of non-Hodgkin lymphoma, said Zelma Chiesa Fuxench, MD, of the department of dermatology, the University of Pennsylvania, Philadelphia. Overall, lymphoma risk was highest in people with severe psoriasis, independent of traditional risk factors and exposure to immunosuppressive medications, Dr. Fuxench said at the annual meeting of the Society for Investigative Dermatology.

Courtesy of the Centers for Disease Control and Prevention (CDC)

Psoriasis affects more than 125 million people worldwide, and severe cases are a major cause of cancer-related mortality. “Prior studies have suggested an increased risk of lymphoma in psoriasis patients, but it is unclear if this due to chronic inflammation, exposure to immunosuppressive therapies, or a combination of both factors,” Dr. Fuxench said.

To further explore these links, she and her associates analyzed electronic medical records from THIN (The Health Information Network), which includes about 12 million patients across the United Kingdom. Adults with psoriasis were matched to up to five nonpsoriatic controls based on date and clinic location. Patients who needed systemic medications or phototherapy were categorized as having severe psoriasis. The final dataset included more than 12,000 such patients, as well as 184,000 patients with mild psoriasis and more than 965,000 patients without psoriasis.

Psoriasis patients were younger and more likely to be overweight, male, and smoke and drink alcohol than patients without psoriasis, Dr. Fuxench said. Almost 80% of patients with severe disease had received systemic therapies, most often methotrexate (70% of systemic treatments) or cyclosporine (10%), while only 1% had received biologics.

Patients with severe psoriasis were more likely to be diagnosed with Hodgkin disease, non-Hodgkin lymphoma, and cutaneous T-cell lymphoma than were patients with mild psoriasis or controls. Over a median follow-up of 5.3 years, 34 patients with severe psoriasis were diagnosed with any type of lymphoma, for an incidence of 5.2 cases per 10,000 person-years (95% confidence interval, 3.7-7.3). In contrast, incidence rates for patients with mild psoriasis and controls were 3.3 and 3.2 cases per 10,000 person-years, respectively, Dr. Fuxench said.

In the multivariable analysis, patients with psoriasis were about 18% more likely to develop any type of lymphoma than were controls, an association that reached statistical significance (adjusted hazard ratio, 1.18; 95% CI, 1.06-1.31). Mild psoriasis increased lymphoma risk by 14%, and severe psoriasis upped it by about 83%, and both associations were statistically significant.

The increase in risk of non-Hodgkin lymphoma was 13% greater with mild psoriasis and 56% greater with severe disease, compared with controls, and these associations also reached statistical significance. Mild psoriasis was not linked to Hodgkin lymphoma, but patients with severe psoriasis were about 250% more likely to develop it than controls, with a trend toward statistical significance (aHR, 2.54; 95% CI, 0.94-6.87).

Finally, severe psoriasis was linked to a more than ninefold increase in risk of cutaneous T-cell lymphoma (aHR, 9.3; 95% CI, 4.1-21.4), while mild psoriasis was linked to about a threefold increase in risk.

“These results were robust in multiple sensitivity analyses, including analyses that excluded patients with rheumatoid arthritis, psoriatic arthritis, or a history of exposure to methotrexate, cyclosporine, or biologics,” Dr. Fuxench said. Future studies should explore the effect of treatment timing and selection on cancer risk, she added. “For those of us who care for these patients, we are increasingly using systemic agents that selectively target the immune system, and these questions will arise in clinics.”

The study’s design made it possible to pinpoint dates of diagnosis more effectively than investigators could estimate disease duration or confirm whether patients initially diagnosed with psoriasis actually had cutaneous T-cell lymphoma, Dr. Fuxench noted. “Ideally, we could have another cohort study of incident psoriasis with prospective follow-up, but lymphoma is so rare that there is currently not enough power [in the THIN database] to determine associations.”

The study was funded by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Fuxench disclosed unrestricted research funding from Pfizer outside the submitted work.

CHICAGO – The anti-CCR4 monoclonal antibody mogamulizumab was superior to other investigator-selected therapies for the treatment of patients with relapsed/refractory adult T-cell leukemia-lymphoma (ATL), based on results from 71 patients in a prospective, multicenter, randomized study reported at the annual meeting of the American Society of Clinical Oncology.

Commonly used cytotoxic regimens provided limited therapeutic benefit for these patients, but mogamulizumab resulted in an objective response rate that supports its therapeutic potential in this setting, reported Dr. Adrienne Alise Phillips of New York Presbyterian/Weill Cornell Medical College, New York.

Mary Jo Dales/Frontline Medical News

A malignancy of T-cells infected with HTLV-1, ATL has a poor prognosis with a median overall survival of less than 3 months in patients with relapsed/refractory disease. CCR4 is expressed in over 90% of ATL patients, and mogamulizumab is approved in Japan for ATL as well as for peripheral T-cell lymphoma and cutaneous T-cell lymphoma.

The 71 patients in the study were from the United States, the European Union and Latin America. The study is the largest randomized clinical trial of relapsed/refractory adult T-cell leukemia-lymphoma thus far conducted. The patients were randomized in 2:1 fashion 47:24 patients) to mogamulizumab, 1.0 mg/kg, given weekly for the first 4-week cycle and then biweekly, or to one of three investigator choice regimens [gemcitabine and oxaliplatin, DHAP (dexamethasone, high-dose cytarabine, and cisplatin), or pralatrexate]. Patients who were in the investigator-choice arm and whose disease progressed were permitted to cross over to mogamulizumab.

The primary endpoint was objective response rate based on modified Tsukasaki criteria and assessed by the treating investigator and in blinded fashion by independent review.

The objective response rate in the mogamulizumab-treated group was 23.4% (11 of 47) by independent review and 34% (16 of 47) by the treating investigator. In the investigator choice group, the overall response rate was 2 of 24 by independent review and 0 of 24 by the treating investigator.

The confirmed objective response rate after 1 month in the mogamulizumab-treated group was 10.6% by independent review and 14.9% by the treating investigator; there were no confirmed responses in the investigator-choice arm. Of 18 patients who crossed over to mogamulizumab, 3 responded. The median duration of response for mogamulizumab was 5 months; one patient had a complete response that lasted over 9 months and the survival data are not yet mature.

Mogamulizumab had few drug-related adverse events, primarily infusion reactions (46.8%), rash/drug eruption (25.5%) and infections (14.9%).

Dr. Phillips disclosed ties to Celgene, Genentech, and Takeda, as well as research funding from Kyowa Hakko Kirin, the sponsor of the study.

Abstract 7501

[email protected]

On Twitter @maryjodales

CHICAGO – The anti-CCR4 monoclonal antibody mogamulizumab was superior to other investigator-selected therapies for the treatment of patients with relapsed/refractory adult T-cell leukemia-lymphoma (ATL), based on results from 71 patients in a prospective, multicenter, randomized study reported at the annual meeting of the American Society of Clinical Oncology.

Commonly used cytotoxic regimens provided limited therapeutic benefit for these patients, but mogamulizumab resulted in an objective response rate that supports its therapeutic potential in this setting, reported Dr. Adrienne Alise Phillips of New York Presbyterian/Weill Cornell Medical College, New York.

Mary Jo Dales/Frontline Medical News

A malignancy of T-cells infected with HTLV-1, ATL has a poor prognosis with a median overall survival of less than 3 months in patients with relapsed/refractory disease. CCR4 is expressed in over 90% of ATL patients, and mogamulizumab is approved in Japan for ATL as well as for peripheral T-cell lymphoma and cutaneous T-cell lymphoma.

The 71 patients in the study were from the United States, the European Union and Latin America. The study is the largest randomized clinical trial of relapsed/refractory adult T-cell leukemia-lymphoma thus far conducted. The patients were randomized in 2:1 fashion 47:24 patients) to mogamulizumab, 1.0 mg/kg, given weekly for the first 4-week cycle and then biweekly, or to one of three investigator choice regimens [gemcitabine and oxaliplatin, DHAP (dexamethasone, high-dose cytarabine, and cisplatin), or pralatrexate]. Patients who were in the investigator-choice arm and whose disease progressed were permitted to cross over to mogamulizumab.

The primary endpoint was objective response rate based on modified Tsukasaki criteria and assessed by the treating investigator and in blinded fashion by independent review.

The objective response rate in the mogamulizumab-treated group was 23.4% (11 of 47) by independent review and 34% (16 of 47) by the treating investigator. In the investigator choice group, the overall response rate was 2 of 24 by independent review and 0 of 24 by the treating investigator.

The confirmed objective response rate after 1 month in the mogamulizumab-treated group was 10.6% by independent review and 14.9% by the treating investigator; there were no confirmed responses in the investigator-choice arm. Of 18 patients who crossed over to mogamulizumab, 3 responded. The median duration of response for mogamulizumab was 5 months; one patient had a complete response that lasted over 9 months and the survival data are not yet mature.

Mogamulizumab had few drug-related adverse events, primarily infusion reactions (46.8%), rash/drug eruption (25.5%) and infections (14.9%).

Dr. Phillips disclosed ties to Celgene, Genentech, and Takeda, as well as research funding from Kyowa Hakko Kirin, the sponsor of the study.

Abstract 7501

[email protected]

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CHICAGO – The anti-CCR4 monoclonal antibody mogamulizumab was superior to other investigator-selected therapies for the treatment of patients with relapsed/refractory adult T-cell leukemia-lymphoma (ATL), based on results from 71 patients in a prospective, multicenter, randomized study reported at the annual meeting of the American Society of Clinical Oncology.

Commonly used cytotoxic regimens provided limited therapeutic benefit for these patients, but mogamulizumab resulted in an objective response rate that supports its therapeutic potential in this setting, reported Dr. Adrienne Alise Phillips of New York Presbyterian/Weill Cornell Medical College, New York.

Mary Jo Dales/Frontline Medical News

A malignancy of T-cells infected with HTLV-1, ATL has a poor prognosis with a median overall survival of less than 3 months in patients with relapsed/refractory disease. CCR4 is expressed in over 90% of ATL patients, and mogamulizumab is approved in Japan for ATL as well as for peripheral T-cell lymphoma and cutaneous T-cell lymphoma.

The 71 patients in the study were from the United States, the European Union and Latin America. The study is the largest randomized clinical trial of relapsed/refractory adult T-cell leukemia-lymphoma thus far conducted. The patients were randomized in 2:1 fashion 47:24 patients) to mogamulizumab, 1.0 mg/kg, given weekly for the first 4-week cycle and then biweekly, or to one of three investigator choice regimens [gemcitabine and oxaliplatin, DHAP (dexamethasone, high-dose cytarabine, and cisplatin), or pralatrexate]. Patients who were in the investigator-choice arm and whose disease progressed were permitted to cross over to mogamulizumab.

The primary endpoint was objective response rate based on modified Tsukasaki criteria and assessed by the treating investigator and in blinded fashion by independent review.

The objective response rate in the mogamulizumab-treated group was 23.4% (11 of 47) by independent review and 34% (16 of 47) by the treating investigator. In the investigator choice group, the overall response rate was 2 of 24 by independent review and 0 of 24 by the treating investigator.

The confirmed objective response rate after 1 month in the mogamulizumab-treated group was 10.6% by independent review and 14.9% by the treating investigator; there were no confirmed responses in the investigator-choice arm. Of 18 patients who crossed over to mogamulizumab, 3 responded. The median duration of response for mogamulizumab was 5 months; one patient had a complete response that lasted over 9 months and the survival data are not yet mature.

Mogamulizumab had few drug-related adverse events, primarily infusion reactions (46.8%), rash/drug eruption (25.5%) and infections (14.9%).

Dr. Phillips disclosed ties to Celgene, Genentech, and Takeda, as well as research funding from Kyowa Hakko Kirin, the sponsor of the study.

Abstract 7501

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On Twitter @maryjodales