B Cell Lymphoma

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

Systemic or hematopoietic stem cell transplantation (HSCT) treatment of HIV-positive lymphoma patients resulted in improved outcomes, compared with nonsystemic treatment, according to the results of a large database study.

Researchers Thejus T. Jayakrishnan, MD, and colleagues examined patients with lymphoma diagnosed between 2004 and 2015 from the National Cancer Database. Patients were categorized as HIV positive and HIV negative. First-line lymphoma treatment was categorized as no systemic therapy reported, systemic therapy, or HSCT. Multivariate analysis was used to predict treatment and survival, according to Dr. Jayakrishnan, a resident at the department of internal medicine, Allegheny Health Network, Pittsburgh.

A total of 11,160 HIV-positive vs. 349,607 HIV-negative patients were analyzed, including mostly men, with a comorbidity index of 0. The most common lymphoma among HIV-positive patients was diffuse large B-cell lymphoma, according to the report in Clinical Lymphoma, Myeloma & Leukemia.

Among HIV-positive patients, 792 had no systemic treatment, 10,328 underwent systemic treatment, and 40 received HSCT treatment. The results showed that treatment of HIV-positive lymphoma patients resulted in improved outcomes: 3-year overall survival was 43.6% for nonsystemic treatment versus 58.1% for systemic (hazard ratio, 0.56; 95% confidence interval, 0.52-0.61; P < .005) versus 62.2% for HSCT therapy (HR, 0.42; 95% CI, 0.14-1.3; P = .08), the lack of significance in the latter could be caused in part by the small number of patients treated. Outcomes for both treatment regimens were lower, however, compared with non-HIV patients.

“The present study demonstrates improvement in survival outcomes for HIV-positive patients with lymphoma with treatments when feasible, but these outcomes are poor when compared to HIV-negative patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Jayakrishnan TT et al. Clin Lymph Myeloma Leuk. 2020 Feb 20. doi: 10.1016/j.clml.2020.06.003.

Systemic or hematopoietic stem cell transplantation (HSCT) treatment of HIV-positive lymphoma patients resulted in improved outcomes, compared with nonsystemic treatment, according to the results of a large database study.

Researchers Thejus T. Jayakrishnan, MD, and colleagues examined patients with lymphoma diagnosed between 2004 and 2015 from the National Cancer Database. Patients were categorized as HIV positive and HIV negative. First-line lymphoma treatment was categorized as no systemic therapy reported, systemic therapy, or HSCT. Multivariate analysis was used to predict treatment and survival, according to Dr. Jayakrishnan, a resident at the department of internal medicine, Allegheny Health Network, Pittsburgh.

A total of 11,160 HIV-positive vs. 349,607 HIV-negative patients were analyzed, including mostly men, with a comorbidity index of 0. The most common lymphoma among HIV-positive patients was diffuse large B-cell lymphoma, according to the report in Clinical Lymphoma, Myeloma & Leukemia.

Among HIV-positive patients, 792 had no systemic treatment, 10,328 underwent systemic treatment, and 40 received HSCT treatment. The results showed that treatment of HIV-positive lymphoma patients resulted in improved outcomes: 3-year overall survival was 43.6% for nonsystemic treatment versus 58.1% for systemic (hazard ratio, 0.56; 95% confidence interval, 0.52-0.61; P < .005) versus 62.2% for HSCT therapy (HR, 0.42; 95% CI, 0.14-1.3; P = .08), the lack of significance in the latter could be caused in part by the small number of patients treated. Outcomes for both treatment regimens were lower, however, compared with non-HIV patients.

“The present study demonstrates improvement in survival outcomes for HIV-positive patients with lymphoma with treatments when feasible, but these outcomes are poor when compared to HIV-negative patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Jayakrishnan TT et al. Clin Lymph Myeloma Leuk. 2020 Feb 20. doi: 10.1016/j.clml.2020.06.003.

Systemic or hematopoietic stem cell transplantation (HSCT) treatment of HIV-positive lymphoma patients resulted in improved outcomes, compared with nonsystemic treatment, according to the results of a large database study.

Researchers Thejus T. Jayakrishnan, MD, and colleagues examined patients with lymphoma diagnosed between 2004 and 2015 from the National Cancer Database. Patients were categorized as HIV positive and HIV negative. First-line lymphoma treatment was categorized as no systemic therapy reported, systemic therapy, or HSCT. Multivariate analysis was used to predict treatment and survival, according to Dr. Jayakrishnan, a resident at the department of internal medicine, Allegheny Health Network, Pittsburgh.

A total of 11,160 HIV-positive vs. 349,607 HIV-negative patients were analyzed, including mostly men, with a comorbidity index of 0. The most common lymphoma among HIV-positive patients was diffuse large B-cell lymphoma, according to the report in Clinical Lymphoma, Myeloma & Leukemia.

Among HIV-positive patients, 792 had no systemic treatment, 10,328 underwent systemic treatment, and 40 received HSCT treatment. The results showed that treatment of HIV-positive lymphoma patients resulted in improved outcomes: 3-year overall survival was 43.6% for nonsystemic treatment versus 58.1% for systemic (hazard ratio, 0.56; 95% confidence interval, 0.52-0.61; P < .005) versus 62.2% for HSCT therapy (HR, 0.42; 95% CI, 0.14-1.3; P = .08), the lack of significance in the latter could be caused in part by the small number of patients treated. Outcomes for both treatment regimens were lower, however, compared with non-HIV patients.

“The present study demonstrates improvement in survival outcomes for HIV-positive patients with lymphoma with treatments when feasible, but these outcomes are poor when compared to HIV-negative patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Jayakrishnan TT et al. Clin Lymph Myeloma Leuk. 2020 Feb 20. doi: 10.1016/j.clml.2020.06.003.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

The US Food and Drug Administration (FDA) has granted accelerated approval of the EZH2 inhibitor tazemetostat (Tazverik, Epizyme, Inc) for the treatment of relapsed or refractory follicular lymphoma in adult patients with tumors harboring an EZH2 mutation.

Eligible patients must have already received at least two prior systemic therapies and have tumors that are positive for an EZH2 mutation, as detected by an FDA-approved test. The FDA has also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc) as a companion diagnostic test for tazemetostat.

The new indication is also for adult patients with relapsed/refractory follicular lymphoma who have no other satisfactory alternative treatment options.

“In our view, there remains no clear standard of care in the relapsed and/or refractory [follicular lymphoma] population, as not all patients benefit from today’s available therapies,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a company press release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe tazemetostat for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory.”

This accelerated approval is based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials, the FDA notes.

Tazemetostat acts as an inhibitor of EZH2 methyltransferase. Earlier this year, the drug was approved for the treatment of metastatic or locally advanced epithelioid sarcoma in cases in which complete resection is not possible. It is the first drug with this mechanism of action and is the first to be indicated for epithelioid sarcoma.

Promising Efficacy in Phase 2 Trial

The new approval for use in follicular lymphoma was based on results from an open-label, single-arm, multicenter phase 2 clinical trial involving patients who had experienced disease progression after being treated with at least two prior systemic regimens. The cohort was divided into two treatment groups: One group consisted of 45 patients with EZH2-activating mutations, the other included 54 patients with wild-type EZH2.

All patients received tazemetostat at 800 mg administered orally twice a day. The primary efficacy outcome measures were overall response rate and duration of response, in accordance with International Working Group Non-Hodgkin Lymphoma criteria.

The median duration of follow-up was 22 months for patients with EZH2-activating mutations and 36 months for those with wild-type tumors.

Among the 45 patients with an EZH2-activating mutation, the median number of lines of prior systemic therapy was 2.0 (range, 1 – 11). In 49% of patients, disease was refractory to rituximab, and in 49%, it was refractory to the patient’s last therapy.

The overall response rate was 69%; 12% of patients achieved a complete response, and 57% achieved a partial response. The median duration of response was 10.9 months and ongoing.

In the cohort of 54 patients with wild-type EZH2, the median number previous therapies was 3.0 (range, 1 – 8); in 59% of patients, disease was refractory to rituximab, and in 41%, it was refractory to the patient’s last therapy.

The overall response rate to tazemetostat treatment was 34%; 4% of patients achieved a complete response, and 30% achieved a partial response. The median duration of response was 13 months.

Serious adverse reactions occurred in 30% of patients. The most common were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Eight patients (8%) discontinued treatment during the trial because of adverse events. There were no reported deaths. No black box warnings have been published, and there are no contraindications.

“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John Leonard, MD, in a company press release. He is associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and New York–Presbyterian Hospital, New York, and an investigator in the ongoing phase 1b/3 confirmatory trial for tazemetostat.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” he commented.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval of the EZH2 inhibitor tazemetostat (Tazverik, Epizyme, Inc) for the treatment of relapsed or refractory follicular lymphoma in adult patients with tumors harboring an EZH2 mutation.

Eligible patients must have already received at least two prior systemic therapies and have tumors that are positive for an EZH2 mutation, as detected by an FDA-approved test. The FDA has also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc) as a companion diagnostic test for tazemetostat.

The new indication is also for adult patients with relapsed/refractory follicular lymphoma who have no other satisfactory alternative treatment options.

“In our view, there remains no clear standard of care in the relapsed and/or refractory [follicular lymphoma] population, as not all patients benefit from today’s available therapies,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a company press release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe tazemetostat for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory.”

This accelerated approval is based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials, the FDA notes.

Tazemetostat acts as an inhibitor of EZH2 methyltransferase. Earlier this year, the drug was approved for the treatment of metastatic or locally advanced epithelioid sarcoma in cases in which complete resection is not possible. It is the first drug with this mechanism of action and is the first to be indicated for epithelioid sarcoma.

Promising Efficacy in Phase 2 Trial

The new approval for use in follicular lymphoma was based on results from an open-label, single-arm, multicenter phase 2 clinical trial involving patients who had experienced disease progression after being treated with at least two prior systemic regimens. The cohort was divided into two treatment groups: One group consisted of 45 patients with EZH2-activating mutations, the other included 54 patients with wild-type EZH2.

All patients received tazemetostat at 800 mg administered orally twice a day. The primary efficacy outcome measures were overall response rate and duration of response, in accordance with International Working Group Non-Hodgkin Lymphoma criteria.

The median duration of follow-up was 22 months for patients with EZH2-activating mutations and 36 months for those with wild-type tumors.

Among the 45 patients with an EZH2-activating mutation, the median number of lines of prior systemic therapy was 2.0 (range, 1 – 11). In 49% of patients, disease was refractory to rituximab, and in 49%, it was refractory to the patient’s last therapy.

The overall response rate was 69%; 12% of patients achieved a complete response, and 57% achieved a partial response. The median duration of response was 10.9 months and ongoing.

In the cohort of 54 patients with wild-type EZH2, the median number previous therapies was 3.0 (range, 1 – 8); in 59% of patients, disease was refractory to rituximab, and in 41%, it was refractory to the patient’s last therapy.

The overall response rate to tazemetostat treatment was 34%; 4% of patients achieved a complete response, and 30% achieved a partial response. The median duration of response was 13 months.

Serious adverse reactions occurred in 30% of patients. The most common were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Eight patients (8%) discontinued treatment during the trial because of adverse events. There were no reported deaths. No black box warnings have been published, and there are no contraindications.

“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John Leonard, MD, in a company press release. He is associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and New York–Presbyterian Hospital, New York, and an investigator in the ongoing phase 1b/3 confirmatory trial for tazemetostat.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” he commented.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval of the EZH2 inhibitor tazemetostat (Tazverik, Epizyme, Inc) for the treatment of relapsed or refractory follicular lymphoma in adult patients with tumors harboring an EZH2 mutation.

Eligible patients must have already received at least two prior systemic therapies and have tumors that are positive for an EZH2 mutation, as detected by an FDA-approved test. The FDA has also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc) as a companion diagnostic test for tazemetostat.

The new indication is also for adult patients with relapsed/refractory follicular lymphoma who have no other satisfactory alternative treatment options.

“In our view, there remains no clear standard of care in the relapsed and/or refractory [follicular lymphoma] population, as not all patients benefit from today’s available therapies,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a company press release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe tazemetostat for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory.”

This accelerated approval is based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials, the FDA notes.

Tazemetostat acts as an inhibitor of EZH2 methyltransferase. Earlier this year, the drug was approved for the treatment of metastatic or locally advanced epithelioid sarcoma in cases in which complete resection is not possible. It is the first drug with this mechanism of action and is the first to be indicated for epithelioid sarcoma.

Promising Efficacy in Phase 2 Trial

The new approval for use in follicular lymphoma was based on results from an open-label, single-arm, multicenter phase 2 clinical trial involving patients who had experienced disease progression after being treated with at least two prior systemic regimens. The cohort was divided into two treatment groups: One group consisted of 45 patients with EZH2-activating mutations, the other included 54 patients with wild-type EZH2.

All patients received tazemetostat at 800 mg administered orally twice a day. The primary efficacy outcome measures were overall response rate and duration of response, in accordance with International Working Group Non-Hodgkin Lymphoma criteria.

The median duration of follow-up was 22 months for patients with EZH2-activating mutations and 36 months for those with wild-type tumors.

Among the 45 patients with an EZH2-activating mutation, the median number of lines of prior systemic therapy was 2.0 (range, 1 – 11). In 49% of patients, disease was refractory to rituximab, and in 49%, it was refractory to the patient’s last therapy.

The overall response rate was 69%; 12% of patients achieved a complete response, and 57% achieved a partial response. The median duration of response was 10.9 months and ongoing.

In the cohort of 54 patients with wild-type EZH2, the median number previous therapies was 3.0 (range, 1 – 8); in 59% of patients, disease was refractory to rituximab, and in 41%, it was refractory to the patient’s last therapy.

The overall response rate to tazemetostat treatment was 34%; 4% of patients achieved a complete response, and 30% achieved a partial response. The median duration of response was 13 months.

Serious adverse reactions occurred in 30% of patients. The most common were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Eight patients (8%) discontinued treatment during the trial because of adverse events. There were no reported deaths. No black box warnings have been published, and there are no contraindications.

“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John Leonard, MD, in a company press release. He is associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and New York–Presbyterian Hospital, New York, and an investigator in the ongoing phase 1b/3 confirmatory trial for tazemetostat.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” he commented.

This article first appeared on Medscape.com.

Adult patients with Burkitt lymphoma can achieve equally sound survival outcomes with dose-adjusted chemotherapy versus high-intensity regimens, but can do so while avoiding the severe toxicities, U.S. study data shows.

Courtesy Wikimedia Commons/Ed Uthman, MD/Creative Commons License

Although Burkitt lymphoma is the most common B-cell non-Hodgkin lymphoma in children, it accounts for only 1% to 2% of adult lymphoma cases.

Highly dose-intensive chemotherapy regimens, developed for children and young adults, have rendered the disease curable. But older patients in particular, and patients with comorbidities such as HIV, can suffer severe adverse effects, as well as late sequelae like second malignancies.

Mark Roschewski, MD, from the lymphoid malignancies branch at the National Cancer Institute in Bethesda, Md., and colleagues therefore examined whether a dose-adjusted regimen would maintain outcomes while reducing toxicities.

Tailoring treatment with etoposide, doxorubicin, and vincristine with prednisone, cyclophosphamide, and rituximab (EPOCH-R) to whether patients had high- or low-risk disease, they achieved 4-year survival rates of higher than 85%.

The research, published by the Journal of Clinical Oncology, also showed that patients taking the regimen, which was well tolerated, had low rates of relapse in the central nervous system.

The team reports that their results with the dose-adjusted regimen “significantly improve on the complexity, cost, and toxicity profile of other regimens,” also highlighting that it is administered on an outpatient basis.

As the outcomes also “compare favorably” with those with high intensity regimens, they say the findings “support our treatment strategies to ameliorate toxicity while maintaining efficacy.”

Importantly, they suggest highly dose-intensive chemotherapy is unnecessary for cure, and carefully defined low-risk patients may be treated with limited chemotherapy.

Dr. Roschewski said in an interview that, in patients aged 40 years and older, dose-adjusted EPOCH-R is “probably the preferred choice,” despite its “weakness” in controlling the disease in patients with active CNS involvement.

However, the “real question” is what to use in younger patients, Dr. Roschewski said, as the “unknown” is whether the additional magnitude of a high-intensity regimen that “gets into the CNS” outweighs the risk of toxicities.

“What was important about our study,” he said, was that patients with CNS involvement “did the worst but it was equally split among patients that died of toxicity and patients that progressed.”

In other words, each choice increases one risk while decreasing another. “So I would have to have that discussion with the patient, and individual patient decisions are typically based on the details,” said Dr. Roschewski.

One issue, however, that could limit the adoption of dose-adjusted EPOCH-R is that, without a randomized study comparing it directly with a high-intensity regimen, clinicians may to stick to what they know.

Dr. Roschewski said that “this is particularly true of more experienced clinicians.”

“They’re less likely, I think, to adopt something else outside of a randomized study because our natural inclination with this disease has always been dose intensity is critical. ... This is a dogma, and to shift from that probably does require a higher level of evidence, at least for some practitioners,” he explained.
 

Further study details

Following a pilot study of dose-adjusted EPOCH-R in 30 adult patients in which the authors say the regimen showed “high efficacy,” they enrolled 113 patients with untreated Burkitt lymphoma at 22 centers between June 2010 and May 2017.

The patients were divided into low-risk and high-risk categories, with low-risk defined as stage 1 or 2 disease, normal lactate dehydrogenase levels, ECOG performance status ≤ 1, and no tumor mass ≥ 7 cm.

High-risk patients were given six cycles of dose-adjusted EPOCH-R (with rituximab on day 1 only) along with CNS prophylaxis or active therapy with intrathecal methotrexate.

In contrast, low-risk patients were given two cycles of dose-adjusted EPOCH-R, with rituximab on days 1 and 5, followed by positron emission tomography.

If that was negative, the patients had one additional treatment cycle and no CNS prophylaxis, but if it was positive, they were given four additional cycles, plus intrathecal methotrexate.

Of the 113 patients enrolled, 79% were male, median age was 49 years, and 62% were aged at least 40 years, including 26% aged at least 60 years.

The team determined that 13% of the patients were of low risk, 87% were high risk, and 11% had cerebrospinal fluid involvement. One-quarter (24.7%) were HIV positive, with a median CD4+ T-cell count of 268 cells/mm³.

The majority (87%) of low-risk patients received three treatment cycles, and 82% of high-risk patents were administered six treatment cycles.

Over a median follow-up of 58.7 months (4.9 years), the 4-year event-free survival (EFS) rate across the whole cohort was 84.5% and overall survival was 87%.

At the time of analysis, all low-risk patients were in remission; among high-risk patients, the 4-year EFS was 82.1% and overall survival was 84.9%.

The team reports that treatment was equally effective across age groups, and irrespective of HIV status and International Prognostic Index risk group.

Only 2% of high-risk patients with no pretreatment evidence of CNS involvement had relapses in the brain parenchyma. Just over half (55%) of patients with cerebrospinal fluid involvement at presentation experienced disease progression or died.

Five patients died of treatment-related toxicity. Grade 3/4 thrombocytopenia occurred during 17% of cycles, and febrile neutropenia was seen during 16%. Tumor lysis syndrome was rare, occurring in 5% of patients.

Next, the researchers are planning on focusing on CNS disease, looking at EPOCH-R as the backbone and adding intrathecal methotrexate and an additional targeted agent with known CNS penetration.

Dr. Roschewski said that is “a very attractive strategy and ... we will initiate enrollment in that study probably in the next couple of months here at the NCI,” he added, noting that it will be an early phase 1 study.

Another issue he identified that “doesn’t get spoken about quite as much but I do think is important is potentially working on supportive care guidelines for how we manage these patients.” Dr. Roschewski explained, “One of the things you see over and over in these Burkitt lymphoma studies is that some patients don’t make it through therapy because they’re so sick at the beginning, and they have certain risks.

“I think simply improving that type of care, independent of what regimen is used, can potentially improve the outcomes across patient groups.”

The study was funded by the National Cancer Institute, National Institutes of Health, AIDS Malignancy Consortium, and the Cancer Therapy Evaluation Program and Lymphoid Malignancies Branch. The authors have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Adult patients with Burkitt lymphoma can achieve equally sound survival outcomes with dose-adjusted chemotherapy versus high-intensity regimens, but can do so while avoiding the severe toxicities, U.S. study data shows.

Courtesy Wikimedia Commons/Ed Uthman, MD/Creative Commons License

Although Burkitt lymphoma is the most common B-cell non-Hodgkin lymphoma in children, it accounts for only 1% to 2% of adult lymphoma cases.

Highly dose-intensive chemotherapy regimens, developed for children and young adults, have rendered the disease curable. But older patients in particular, and patients with comorbidities such as HIV, can suffer severe adverse effects, as well as late sequelae like second malignancies.

Mark Roschewski, MD, from the lymphoid malignancies branch at the National Cancer Institute in Bethesda, Md., and colleagues therefore examined whether a dose-adjusted regimen would maintain outcomes while reducing toxicities.

Tailoring treatment with etoposide, doxorubicin, and vincristine with prednisone, cyclophosphamide, and rituximab (EPOCH-R) to whether patients had high- or low-risk disease, they achieved 4-year survival rates of higher than 85%.

The research, published by the Journal of Clinical Oncology, also showed that patients taking the regimen, which was well tolerated, had low rates of relapse in the central nervous system.

The team reports that their results with the dose-adjusted regimen “significantly improve on the complexity, cost, and toxicity profile of other regimens,” also highlighting that it is administered on an outpatient basis.

As the outcomes also “compare favorably” with those with high intensity regimens, they say the findings “support our treatment strategies to ameliorate toxicity while maintaining efficacy.”

Importantly, they suggest highly dose-intensive chemotherapy is unnecessary for cure, and carefully defined low-risk patients may be treated with limited chemotherapy.

Dr. Roschewski said in an interview that, in patients aged 40 years and older, dose-adjusted EPOCH-R is “probably the preferred choice,” despite its “weakness” in controlling the disease in patients with active CNS involvement.

However, the “real question” is what to use in younger patients, Dr. Roschewski said, as the “unknown” is whether the additional magnitude of a high-intensity regimen that “gets into the CNS” outweighs the risk of toxicities.

“What was important about our study,” he said, was that patients with CNS involvement “did the worst but it was equally split among patients that died of toxicity and patients that progressed.”

In other words, each choice increases one risk while decreasing another. “So I would have to have that discussion with the patient, and individual patient decisions are typically based on the details,” said Dr. Roschewski.

One issue, however, that could limit the adoption of dose-adjusted EPOCH-R is that, without a randomized study comparing it directly with a high-intensity regimen, clinicians may to stick to what they know.

Dr. Roschewski said that “this is particularly true of more experienced clinicians.”

“They’re less likely, I think, to adopt something else outside of a randomized study because our natural inclination with this disease has always been dose intensity is critical. ... This is a dogma, and to shift from that probably does require a higher level of evidence, at least for some practitioners,” he explained.
 

Further study details

Following a pilot study of dose-adjusted EPOCH-R in 30 adult patients in which the authors say the regimen showed “high efficacy,” they enrolled 113 patients with untreated Burkitt lymphoma at 22 centers between June 2010 and May 2017.

The patients were divided into low-risk and high-risk categories, with low-risk defined as stage 1 or 2 disease, normal lactate dehydrogenase levels, ECOG performance status ≤ 1, and no tumor mass ≥ 7 cm.

High-risk patients were given six cycles of dose-adjusted EPOCH-R (with rituximab on day 1 only) along with CNS prophylaxis or active therapy with intrathecal methotrexate.

In contrast, low-risk patients were given two cycles of dose-adjusted EPOCH-R, with rituximab on days 1 and 5, followed by positron emission tomography.

If that was negative, the patients had one additional treatment cycle and no CNS prophylaxis, but if it was positive, they were given four additional cycles, plus intrathecal methotrexate.

Of the 113 patients enrolled, 79% were male, median age was 49 years, and 62% were aged at least 40 years, including 26% aged at least 60 years.

The team determined that 13% of the patients were of low risk, 87% were high risk, and 11% had cerebrospinal fluid involvement. One-quarter (24.7%) were HIV positive, with a median CD4+ T-cell count of 268 cells/mm³.

The majority (87%) of low-risk patients received three treatment cycles, and 82% of high-risk patents were administered six treatment cycles.

Over a median follow-up of 58.7 months (4.9 years), the 4-year event-free survival (EFS) rate across the whole cohort was 84.5% and overall survival was 87%.

At the time of analysis, all low-risk patients were in remission; among high-risk patients, the 4-year EFS was 82.1% and overall survival was 84.9%.

The team reports that treatment was equally effective across age groups, and irrespective of HIV status and International Prognostic Index risk group.

Only 2% of high-risk patients with no pretreatment evidence of CNS involvement had relapses in the brain parenchyma. Just over half (55%) of patients with cerebrospinal fluid involvement at presentation experienced disease progression or died.

Five patients died of treatment-related toxicity. Grade 3/4 thrombocytopenia occurred during 17% of cycles, and febrile neutropenia was seen during 16%. Tumor lysis syndrome was rare, occurring in 5% of patients.

Next, the researchers are planning on focusing on CNS disease, looking at EPOCH-R as the backbone and adding intrathecal methotrexate and an additional targeted agent with known CNS penetration.

Dr. Roschewski said that is “a very attractive strategy and ... we will initiate enrollment in that study probably in the next couple of months here at the NCI,” he added, noting that it will be an early phase 1 study.

Another issue he identified that “doesn’t get spoken about quite as much but I do think is important is potentially working on supportive care guidelines for how we manage these patients.” Dr. Roschewski explained, “One of the things you see over and over in these Burkitt lymphoma studies is that some patients don’t make it through therapy because they’re so sick at the beginning, and they have certain risks.

“I think simply improving that type of care, independent of what regimen is used, can potentially improve the outcomes across patient groups.”

The study was funded by the National Cancer Institute, National Institutes of Health, AIDS Malignancy Consortium, and the Cancer Therapy Evaluation Program and Lymphoid Malignancies Branch. The authors have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Adult patients with Burkitt lymphoma can achieve equally sound survival outcomes with dose-adjusted chemotherapy versus high-intensity regimens, but can do so while avoiding the severe toxicities, U.S. study data shows.

Courtesy Wikimedia Commons/Ed Uthman, MD/Creative Commons License

Although Burkitt lymphoma is the most common B-cell non-Hodgkin lymphoma in children, it accounts for only 1% to 2% of adult lymphoma cases.

Highly dose-intensive chemotherapy regimens, developed for children and young adults, have rendered the disease curable. But older patients in particular, and patients with comorbidities such as HIV, can suffer severe adverse effects, as well as late sequelae like second malignancies.

Mark Roschewski, MD, from the lymphoid malignancies branch at the National Cancer Institute in Bethesda, Md., and colleagues therefore examined whether a dose-adjusted regimen would maintain outcomes while reducing toxicities.

Tailoring treatment with etoposide, doxorubicin, and vincristine with prednisone, cyclophosphamide, and rituximab (EPOCH-R) to whether patients had high- or low-risk disease, they achieved 4-year survival rates of higher than 85%.

The research, published by the Journal of Clinical Oncology, also showed that patients taking the regimen, which was well tolerated, had low rates of relapse in the central nervous system.

The team reports that their results with the dose-adjusted regimen “significantly improve on the complexity, cost, and toxicity profile of other regimens,” also highlighting that it is administered on an outpatient basis.

As the outcomes also “compare favorably” with those with high intensity regimens, they say the findings “support our treatment strategies to ameliorate toxicity while maintaining efficacy.”

Importantly, they suggest highly dose-intensive chemotherapy is unnecessary for cure, and carefully defined low-risk patients may be treated with limited chemotherapy.

Dr. Roschewski said in an interview that, in patients aged 40 years and older, dose-adjusted EPOCH-R is “probably the preferred choice,” despite its “weakness” in controlling the disease in patients with active CNS involvement.

However, the “real question” is what to use in younger patients, Dr. Roschewski said, as the “unknown” is whether the additional magnitude of a high-intensity regimen that “gets into the CNS” outweighs the risk of toxicities.

“What was important about our study,” he said, was that patients with CNS involvement “did the worst but it was equally split among patients that died of toxicity and patients that progressed.”

In other words, each choice increases one risk while decreasing another. “So I would have to have that discussion with the patient, and individual patient decisions are typically based on the details,” said Dr. Roschewski.

One issue, however, that could limit the adoption of dose-adjusted EPOCH-R is that, without a randomized study comparing it directly with a high-intensity regimen, clinicians may to stick to what they know.

Dr. Roschewski said that “this is particularly true of more experienced clinicians.”

“They’re less likely, I think, to adopt something else outside of a randomized study because our natural inclination with this disease has always been dose intensity is critical. ... This is a dogma, and to shift from that probably does require a higher level of evidence, at least for some practitioners,” he explained.
 

Further study details

Following a pilot study of dose-adjusted EPOCH-R in 30 adult patients in which the authors say the regimen showed “high efficacy,” they enrolled 113 patients with untreated Burkitt lymphoma at 22 centers between June 2010 and May 2017.

The patients were divided into low-risk and high-risk categories, with low-risk defined as stage 1 or 2 disease, normal lactate dehydrogenase levels, ECOG performance status ≤ 1, and no tumor mass ≥ 7 cm.

High-risk patients were given six cycles of dose-adjusted EPOCH-R (with rituximab on day 1 only) along with CNS prophylaxis or active therapy with intrathecal methotrexate.

In contrast, low-risk patients were given two cycles of dose-adjusted EPOCH-R, with rituximab on days 1 and 5, followed by positron emission tomography.

If that was negative, the patients had one additional treatment cycle and no CNS prophylaxis, but if it was positive, they were given four additional cycles, plus intrathecal methotrexate.

Of the 113 patients enrolled, 79% were male, median age was 49 years, and 62% were aged at least 40 years, including 26% aged at least 60 years.

The team determined that 13% of the patients were of low risk, 87% were high risk, and 11% had cerebrospinal fluid involvement. One-quarter (24.7%) were HIV positive, with a median CD4+ T-cell count of 268 cells/mm³.

The majority (87%) of low-risk patients received three treatment cycles, and 82% of high-risk patents were administered six treatment cycles.

Over a median follow-up of 58.7 months (4.9 years), the 4-year event-free survival (EFS) rate across the whole cohort was 84.5% and overall survival was 87%.

At the time of analysis, all low-risk patients were in remission; among high-risk patients, the 4-year EFS was 82.1% and overall survival was 84.9%.

The team reports that treatment was equally effective across age groups, and irrespective of HIV status and International Prognostic Index risk group.

Only 2% of high-risk patients with no pretreatment evidence of CNS involvement had relapses in the brain parenchyma. Just over half (55%) of patients with cerebrospinal fluid involvement at presentation experienced disease progression or died.

Five patients died of treatment-related toxicity. Grade 3/4 thrombocytopenia occurred during 17% of cycles, and febrile neutropenia was seen during 16%. Tumor lysis syndrome was rare, occurring in 5% of patients.

Next, the researchers are planning on focusing on CNS disease, looking at EPOCH-R as the backbone and adding intrathecal methotrexate and an additional targeted agent with known CNS penetration.

Dr. Roschewski said that is “a very attractive strategy and ... we will initiate enrollment in that study probably in the next couple of months here at the NCI,” he added, noting that it will be an early phase 1 study.

Another issue he identified that “doesn’t get spoken about quite as much but I do think is important is potentially working on supportive care guidelines for how we manage these patients.” Dr. Roschewski explained, “One of the things you see over and over in these Burkitt lymphoma studies is that some patients don’t make it through therapy because they’re so sick at the beginning, and they have certain risks.

“I think simply improving that type of care, independent of what regimen is used, can potentially improve the outcomes across patient groups.”

The study was funded by the National Cancer Institute, National Institutes of Health, AIDS Malignancy Consortium, and the Cancer Therapy Evaluation Program and Lymphoid Malignancies Branch. The authors have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

In its updated cancer prevention guidelines, the American Cancer Society now recommends that “it is best not to drink alcohol.”

Previously, ACS suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive.

The revised guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity.

But importantly, there is also a call for action from public, private, and community organizations to work to together to increase access to affordable, nutritious foods and physical activity.

“Making healthy choices can be challenging for many, and there are strategies included in the guidelines that communities can undertake to help reduce barriers to eating well and physical activity,” said Laura Makaroff, DO, American Cancer Society senior vice president. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support.”

The guidelines were published in CA: A Cancer Journal for Clinicians.

The link between cancer and lifestyle factors has long been established, and for the past 4 decades, both government and leading nonprofit health organizations, including the ACS and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), have released cancer prevention guidelines and recommendations that focus on managing weight, diet, physical activity, and alcohol consumption.

In 2012, the ACS issued guidelines on diet and physical activity, and their current guideline is largely based on the WCRF/AICR systematic reviews and Continuous Update Project reports, which were last updated in 2018. The ACS guidelines also incorporated systematic reviews conducted by the International Agency on Cancer Research (IARC) and the U.S. Department of Agriculture and the Department of Health and Human Services (USDA/HHS) and other analyses that were published since the WCRF/AICR recommendations were released.
 

Emphasis on three areas

The differences between the old guidelines and the update do not differ dramatically, but Makaroff highlighted a few areas that have increased emphasis.

Time spent being physically active is critical. The recommendation has changed to encourage adults to engage in 150-300 minutes (2.5-5 hours) of moderate-intensity physical activity, or 75-150 minutes (1.25-2.5 hours) of vigorous-intensity physical activity, or an equivalent combination, per week. Achieving or exceeding the upper limit of 300 minutes is optimal.

“That is more than what we have recommended in the past, along with the continued message that children and adolescents engage in at least 1 hour of moderate- or vigorous-intensity activity each day,” she told Medscape Medical News.

The ACS has also increased emphasis on reducing the consumption of processed and red meat. “This is part of a healthy eating pattern and making sure that people are eating food that is high in nutrients that help achieve and maintain a healthy body weight,” said Makaroff.

A healthy diet should include a variety of dark green, red, and orange vegetables; fiber-rich legumes; and fruits with a variety of colors and whole grains, according to the guidelines. Sugar-sweetened beverages, highly processed foods, and refined grain products should be limited or avoided.

The revised dietary recommendations reflect a shift from a “reductionist or nutrient-centric” approach to one that is more “holistic” and that focuses on dietary patterns. In contrast to a focus on individual nutrients and bioactive compounds, the new approach is more consistent with what and how people actually eat, ACS points out.

The third area that Makaroff highlighted is alcohol, where the recommendation is to avoid or limit consumption. “The current update says not to drink alcohol, which is in line with the scientific evidence, but for those people who choose to drink alcohol, to limit it to one drink per day for women and two drinks per day for men.”

Thus, the change here is that the previous guideline only recommended limiting alcohol consumption, while the update suggests that, optimally, it should be avoided completely.

The ACS has also called for community involvement to help implement these goals: “Public, private, and community organizations should work collaboratively at national, state, and local levels to develop, advocate for, and implement policy and environmental changes that increase access to affordable, nutritious foods; provide safe, enjoyable, and accessible opportunities for physical activity; and limit alcohol for all individuals.”
 

No smoking guns

Commenting on the guidelines, Steven K. Clinton, MD, PhD, associate director of the Center for Advanced Functional Foods Research and Entrepreneurship at the Ohio State University, Columbus, explained that he didn’t view the change in alcohol as that much of an evolution. “It’s been 8 years since they revised their overall guidelines, and during that time frame, there has been an enormous growth in the evidence that has been used by many organizations,” he said.

Clinton noted that the guidelines are consistent with the whole body of current scientific literature. “It’s very easy to go to the document and look for the ‘smoking gun’ – but the smoking gun is really not one thing,” he said. “It’s a pattern, and what dietitians and nutritionists are telling people is that you need to orchestrate a healthy lifestyle and diet, with a diet that has a foundation of fruits, vegetables, whole grains, and modest intake of refined grains and meat. You are orchestrating an entire pattern to get the maximum benefit.”

Makaroff is an employee of the ACS. Clinton has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In its updated cancer prevention guidelines, the American Cancer Society now recommends that “it is best not to drink alcohol.”

Previously, ACS suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive.

The revised guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity.

But importantly, there is also a call for action from public, private, and community organizations to work to together to increase access to affordable, nutritious foods and physical activity.

“Making healthy choices can be challenging for many, and there are strategies included in the guidelines that communities can undertake to help reduce barriers to eating well and physical activity,” said Laura Makaroff, DO, American Cancer Society senior vice president. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support.”

The guidelines were published in CA: A Cancer Journal for Clinicians.

The link between cancer and lifestyle factors has long been established, and for the past 4 decades, both government and leading nonprofit health organizations, including the ACS and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), have released cancer prevention guidelines and recommendations that focus on managing weight, diet, physical activity, and alcohol consumption.

In 2012, the ACS issued guidelines on diet and physical activity, and their current guideline is largely based on the WCRF/AICR systematic reviews and Continuous Update Project reports, which were last updated in 2018. The ACS guidelines also incorporated systematic reviews conducted by the International Agency on Cancer Research (IARC) and the U.S. Department of Agriculture and the Department of Health and Human Services (USDA/HHS) and other analyses that were published since the WCRF/AICR recommendations were released.
 

Emphasis on three areas

The differences between the old guidelines and the update do not differ dramatically, but Makaroff highlighted a few areas that have increased emphasis.

Time spent being physically active is critical. The recommendation has changed to encourage adults to engage in 150-300 minutes (2.5-5 hours) of moderate-intensity physical activity, or 75-150 minutes (1.25-2.5 hours) of vigorous-intensity physical activity, or an equivalent combination, per week. Achieving or exceeding the upper limit of 300 minutes is optimal.

“That is more than what we have recommended in the past, along with the continued message that children and adolescents engage in at least 1 hour of moderate- or vigorous-intensity activity each day,” she told Medscape Medical News.

The ACS has also increased emphasis on reducing the consumption of processed and red meat. “This is part of a healthy eating pattern and making sure that people are eating food that is high in nutrients that help achieve and maintain a healthy body weight,” said Makaroff.

A healthy diet should include a variety of dark green, red, and orange vegetables; fiber-rich legumes; and fruits with a variety of colors and whole grains, according to the guidelines. Sugar-sweetened beverages, highly processed foods, and refined grain products should be limited or avoided.

The revised dietary recommendations reflect a shift from a “reductionist or nutrient-centric” approach to one that is more “holistic” and that focuses on dietary patterns. In contrast to a focus on individual nutrients and bioactive compounds, the new approach is more consistent with what and how people actually eat, ACS points out.

The third area that Makaroff highlighted is alcohol, where the recommendation is to avoid or limit consumption. “The current update says not to drink alcohol, which is in line with the scientific evidence, but for those people who choose to drink alcohol, to limit it to one drink per day for women and two drinks per day for men.”

Thus, the change here is that the previous guideline only recommended limiting alcohol consumption, while the update suggests that, optimally, it should be avoided completely.

The ACS has also called for community involvement to help implement these goals: “Public, private, and community organizations should work collaboratively at national, state, and local levels to develop, advocate for, and implement policy and environmental changes that increase access to affordable, nutritious foods; provide safe, enjoyable, and accessible opportunities for physical activity; and limit alcohol for all individuals.”
 

No smoking guns

Commenting on the guidelines, Steven K. Clinton, MD, PhD, associate director of the Center for Advanced Functional Foods Research and Entrepreneurship at the Ohio State University, Columbus, explained that he didn’t view the change in alcohol as that much of an evolution. “It’s been 8 years since they revised their overall guidelines, and during that time frame, there has been an enormous growth in the evidence that has been used by many organizations,” he said.

Clinton noted that the guidelines are consistent with the whole body of current scientific literature. “It’s very easy to go to the document and look for the ‘smoking gun’ – but the smoking gun is really not one thing,” he said. “It’s a pattern, and what dietitians and nutritionists are telling people is that you need to orchestrate a healthy lifestyle and diet, with a diet that has a foundation of fruits, vegetables, whole grains, and modest intake of refined grains and meat. You are orchestrating an entire pattern to get the maximum benefit.”

Makaroff is an employee of the ACS. Clinton has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In its updated cancer prevention guidelines, the American Cancer Society now recommends that “it is best not to drink alcohol.”

Previously, ACS suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive.

The revised guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity.

But importantly, there is also a call for action from public, private, and community organizations to work to together to increase access to affordable, nutritious foods and physical activity.

“Making healthy choices can be challenging for many, and there are strategies included in the guidelines that communities can undertake to help reduce barriers to eating well and physical activity,” said Laura Makaroff, DO, American Cancer Society senior vice president. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support.”

The guidelines were published in CA: A Cancer Journal for Clinicians.

The link between cancer and lifestyle factors has long been established, and for the past 4 decades, both government and leading nonprofit health organizations, including the ACS and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), have released cancer prevention guidelines and recommendations that focus on managing weight, diet, physical activity, and alcohol consumption.

In 2012, the ACS issued guidelines on diet and physical activity, and their current guideline is largely based on the WCRF/AICR systematic reviews and Continuous Update Project reports, which were last updated in 2018. The ACS guidelines also incorporated systematic reviews conducted by the International Agency on Cancer Research (IARC) and the U.S. Department of Agriculture and the Department of Health and Human Services (USDA/HHS) and other analyses that were published since the WCRF/AICR recommendations were released.
 

Emphasis on three areas

The differences between the old guidelines and the update do not differ dramatically, but Makaroff highlighted a few areas that have increased emphasis.

Time spent being physically active is critical. The recommendation has changed to encourage adults to engage in 150-300 minutes (2.5-5 hours) of moderate-intensity physical activity, or 75-150 minutes (1.25-2.5 hours) of vigorous-intensity physical activity, or an equivalent combination, per week. Achieving or exceeding the upper limit of 300 minutes is optimal.

“That is more than what we have recommended in the past, along with the continued message that children and adolescents engage in at least 1 hour of moderate- or vigorous-intensity activity each day,” she told Medscape Medical News.

The ACS has also increased emphasis on reducing the consumption of processed and red meat. “This is part of a healthy eating pattern and making sure that people are eating food that is high in nutrients that help achieve and maintain a healthy body weight,” said Makaroff.

A healthy diet should include a variety of dark green, red, and orange vegetables; fiber-rich legumes; and fruits with a variety of colors and whole grains, according to the guidelines. Sugar-sweetened beverages, highly processed foods, and refined grain products should be limited or avoided.

The revised dietary recommendations reflect a shift from a “reductionist or nutrient-centric” approach to one that is more “holistic” and that focuses on dietary patterns. In contrast to a focus on individual nutrients and bioactive compounds, the new approach is more consistent with what and how people actually eat, ACS points out.

The third area that Makaroff highlighted is alcohol, where the recommendation is to avoid or limit consumption. “The current update says not to drink alcohol, which is in line with the scientific evidence, but for those people who choose to drink alcohol, to limit it to one drink per day for women and two drinks per day for men.”

Thus, the change here is that the previous guideline only recommended limiting alcohol consumption, while the update suggests that, optimally, it should be avoided completely.

The ACS has also called for community involvement to help implement these goals: “Public, private, and community organizations should work collaboratively at national, state, and local levels to develop, advocate for, and implement policy and environmental changes that increase access to affordable, nutritious foods; provide safe, enjoyable, and accessible opportunities for physical activity; and limit alcohol for all individuals.”
 

No smoking guns

Commenting on the guidelines, Steven K. Clinton, MD, PhD, associate director of the Center for Advanced Functional Foods Research and Entrepreneurship at the Ohio State University, Columbus, explained that he didn’t view the change in alcohol as that much of an evolution. “It’s been 8 years since they revised their overall guidelines, and during that time frame, there has been an enormous growth in the evidence that has been used by many organizations,” he said.

Clinton noted that the guidelines are consistent with the whole body of current scientific literature. “It’s very easy to go to the document and look for the ‘smoking gun’ – but the smoking gun is really not one thing,” he said. “It’s a pattern, and what dietitians and nutritionists are telling people is that you need to orchestrate a healthy lifestyle and diet, with a diet that has a foundation of fruits, vegetables, whole grains, and modest intake of refined grains and meat. You are orchestrating an entire pattern to get the maximum benefit.”

Makaroff is an employee of the ACS. Clinton has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

The addition of rituximab to standard chemotherapy was a more effective therapy in children and adolescents with high-risk, high-grade,mature B-cell non-Hodgkin lymphoma than the use of chemotherapy alone, according to a study published in the New England Journal of Medicine. The addition of rituximab resulted in long-term complete remission in the vast majority of patients, reported Veronique Minard-Colin, MD, of the Gustave Roussy Institute, Villejuif Cedex, France, and her colleagues on behalf of the European Intergroup for Childhood Non-Hodgkin Lymphoma and the Children’s Oncology Group.

Courtesy Wikimedia Commons/Ed Uthman, MD/Creative Commons License

The researchers performed an open-label, randomized, phase 3 trial of 328 patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin’s lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. There were 164 patients assigned to each group. The primary end point of the study was event-free survival; overall survival and toxic effects were also followed.

The majority of patients had Burkitt’s lymphoma: 139 (84.8%) in the rituximab-chemotherapy group and 142 (86.6%) in the chemotherapy-alone group, with diffuse large B-cell lymphoma being the second most common cancer: 19 (11.6%) vs. 12 (7.3%), respectively.

Event-free survival at 3 years was 93.9% (95% confidence interval, 89.1-96.7) in the rituximab-chemotherapy group and 82.3% (95% CI, 75.7-87.5) in the chemotherapy group.

Higher 3-year overall survival was also observed (95.1% in the rituximab-chemotherapy group vs. 87.3% in the chemotherapy group; hazard ratio for death, 0.36; 95% CI, 0.16 -0.82).

Eight patients in the rituximab-chemotherapy group died (4 deaths were disease related, 3 were treatment related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths disease related, and 3 treatment related); HR, 0.36; 95% CI, 0.16-0.82.

The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab-chemotherapy group and 24.2% in the chemotherapy group, a nonsignificant difference (P = .07). However, around twice as many patients in the rituximab-chemotherapy group had a low IgG level at 1 year after trial inclusion, compared with the chemotherapy-alone group, which could indicate the potential for more frequent infections in the long term, the researchers stated.

“An assessment of the long-term effects of combining rituximab with this chemotherapy regimen in children with non-Hodgkin lymphoma, including data on immune status, will be useful,” they added.

The study was funded by the French Ministry of Health, Cancer Research UK, the National Institute for Health Research Clinical Research Network, the Children’s Cancer Foundation Hong Kong, the U.S. National Cancer Institute, and F. Hoffmann–La Roche–Genentech. Several of the authors reported consulting for and institutional and grant funding from F. Hoffmann-LaRoche, which markets rituximab, as well as relationships with other pharmaceutical companies.

[email protected]

SOURCE: Minard-Colin V et al. N Engl J Med. 2020;382:2207-19.

The addition of rituximab to standard chemotherapy was a more effective therapy in children and adolescents with high-risk, high-grade,mature B-cell non-Hodgkin lymphoma than the use of chemotherapy alone, according to a study published in the New England Journal of Medicine. The addition of rituximab resulted in long-term complete remission in the vast majority of patients, reported Veronique Minard-Colin, MD, of the Gustave Roussy Institute, Villejuif Cedex, France, and her colleagues on behalf of the European Intergroup for Childhood Non-Hodgkin Lymphoma and the Children’s Oncology Group.

Courtesy Wikimedia Commons/Ed Uthman, MD/Creative Commons License

The researchers performed an open-label, randomized, phase 3 trial of 328 patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin’s lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. There were 164 patients assigned to each group. The primary end point of the study was event-free survival; overall survival and toxic effects were also followed.

The majority of patients had Burkitt’s lymphoma: 139 (84.8%) in the rituximab-chemotherapy group and 142 (86.6%) in the chemotherapy-alone group, with diffuse large B-cell lymphoma being the second most common cancer: 19 (11.6%) vs. 12 (7.3%), respectively.

Event-free survival at 3 years was 93.9% (95% confidence interval, 89.1-96.7) in the rituximab-chemotherapy group and 82.3% (95% CI, 75.7-87.5) in the chemotherapy group.

Higher 3-year overall survival was also observed (95.1% in the rituximab-chemotherapy group vs. 87.3% in the chemotherapy group; hazard ratio for death, 0.36; 95% CI, 0.16 -0.82).

Eight patients in the rituximab-chemotherapy group died (4 deaths were disease related, 3 were treatment related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths disease related, and 3 treatment related); HR, 0.36; 95% CI, 0.16-0.82.

The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab-chemotherapy group and 24.2% in the chemotherapy group, a nonsignificant difference (P = .07). However, around twice as many patients in the rituximab-chemotherapy group had a low IgG level at 1 year after trial inclusion, compared with the chemotherapy-alone group, which could indicate the potential for more frequent infections in the long term, the researchers stated.

“An assessment of the long-term effects of combining rituximab with this chemotherapy regimen in children with non-Hodgkin lymphoma, including data on immune status, will be useful,” they added.

The study was funded by the French Ministry of Health, Cancer Research UK, the National Institute for Health Research Clinical Research Network, the Children’s Cancer Foundation Hong Kong, the U.S. National Cancer Institute, and F. Hoffmann–La Roche–Genentech. Several of the authors reported consulting for and institutional and grant funding from F. Hoffmann-LaRoche, which markets rituximab, as well as relationships with other pharmaceutical companies.

[email protected]

SOURCE: Minard-Colin V et al. N Engl J Med. 2020;382:2207-19.

The addition of rituximab to standard chemotherapy was a more effective therapy in children and adolescents with high-risk, high-grade,mature B-cell non-Hodgkin lymphoma than the use of chemotherapy alone, according to a study published in the New England Journal of Medicine. The addition of rituximab resulted in long-term complete remission in the vast majority of patients, reported Veronique Minard-Colin, MD, of the Gustave Roussy Institute, Villejuif Cedex, France, and her colleagues on behalf of the European Intergroup for Childhood Non-Hodgkin Lymphoma and the Children’s Oncology Group.

Courtesy Wikimedia Commons/Ed Uthman, MD/Creative Commons License

The researchers performed an open-label, randomized, phase 3 trial of 328 patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin’s lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. There were 164 patients assigned to each group. The primary end point of the study was event-free survival; overall survival and toxic effects were also followed.

The majority of patients had Burkitt’s lymphoma: 139 (84.8%) in the rituximab-chemotherapy group and 142 (86.6%) in the chemotherapy-alone group, with diffuse large B-cell lymphoma being the second most common cancer: 19 (11.6%) vs. 12 (7.3%), respectively.

Event-free survival at 3 years was 93.9% (95% confidence interval, 89.1-96.7) in the rituximab-chemotherapy group and 82.3% (95% CI, 75.7-87.5) in the chemotherapy group.

Higher 3-year overall survival was also observed (95.1% in the rituximab-chemotherapy group vs. 87.3% in the chemotherapy group; hazard ratio for death, 0.36; 95% CI, 0.16 -0.82).

Eight patients in the rituximab-chemotherapy group died (4 deaths were disease related, 3 were treatment related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths disease related, and 3 treatment related); HR, 0.36; 95% CI, 0.16-0.82.

The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab-chemotherapy group and 24.2% in the chemotherapy group, a nonsignificant difference (P = .07). However, around twice as many patients in the rituximab-chemotherapy group had a low IgG level at 1 year after trial inclusion, compared with the chemotherapy-alone group, which could indicate the potential for more frequent infections in the long term, the researchers stated.

“An assessment of the long-term effects of combining rituximab with this chemotherapy regimen in children with non-Hodgkin lymphoma, including data on immune status, will be useful,” they added.

The study was funded by the French Ministry of Health, Cancer Research UK, the National Institute for Health Research Clinical Research Network, the Children’s Cancer Foundation Hong Kong, the U.S. National Cancer Institute, and F. Hoffmann–La Roche–Genentech. Several of the authors reported consulting for and institutional and grant funding from F. Hoffmann-LaRoche, which markets rituximab, as well as relationships with other pharmaceutical companies.

[email protected]

SOURCE: Minard-Colin V et al. N Engl J Med. 2020;382:2207-19.

Academic centers had significantly improved overall survival of patients with diffuse large B-cell lymphoma (DLBCL), according to a large database study.

Nephron/Wikimedia Commons/CC BY-SA 3.0

Researchers used the U.S. National Cancer Database to identify patients with a diagnosis of DLBCL from 2004 to 2015. The researchers identified 27,690 patients for the study. The majority of the patients were white (89.3%) and men (53.7%), with an average age of 64 years. A total of 57.6% of the patients had been treated at nonacademic centers and 42.4% at academic centers, and no notable differences were seen in facility choice among the low- to high-risk International Prognostic Index (IPI) risk categories.

The researchers found that overall survival of the DLBCL patients at academic centers was 108.3 months versus 74.5 months at nonacademic centers (P < .001), according to the study published in Clinical Lymphoma, Myeloma and Leukemia.

In addition, the median survival for patients with high-risk disease treated at academic centers was more than twice that of high-risk patients treated at nonacademic centers (33.5 months vs. 14.4 months, respectively; P < .001). Although the median survival for the other risk categories was also improved, the difference was less pronounced in the groups with lower IPI scores, according to the researchers.

Long-term overall survival for all patients with DLBCL at academic centers was significantly improved at both 5 and 10 years (59% and 43% survival, respectively) compared with those patients treated at nonacademic centers (51% and 35% survival, respectively; P < .001).

Speculating on factors that might be involved in this discrepancy in survival, the researchers suggested that academic centers might provide increased access to clinical trials, improved physician expertise, as well as improved treatment facilities and supportive care.

“Our results should prompt further investigation in precisely determining the factors that might support this significant effect on decreased survival among those treated in the community and help ameliorate this discrepancy,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Ermann DA et al. Clin Lymphoma Myeloma Leuk. 2020;20(4): e17483.

Academic centers had significantly improved overall survival of patients with diffuse large B-cell lymphoma (DLBCL), according to a large database study.

Nephron/Wikimedia Commons/CC BY-SA 3.0

Researchers used the U.S. National Cancer Database to identify patients with a diagnosis of DLBCL from 2004 to 2015. The researchers identified 27,690 patients for the study. The majority of the patients were white (89.3%) and men (53.7%), with an average age of 64 years. A total of 57.6% of the patients had been treated at nonacademic centers and 42.4% at academic centers, and no notable differences were seen in facility choice among the low- to high-risk International Prognostic Index (IPI) risk categories.

The researchers found that overall survival of the DLBCL patients at academic centers was 108.3 months versus 74.5 months at nonacademic centers (P < .001), according to the study published in Clinical Lymphoma, Myeloma and Leukemia.

In addition, the median survival for patients with high-risk disease treated at academic centers was more than twice that of high-risk patients treated at nonacademic centers (33.5 months vs. 14.4 months, respectively; P < .001). Although the median survival for the other risk categories was also improved, the difference was less pronounced in the groups with lower IPI scores, according to the researchers.

Long-term overall survival for all patients with DLBCL at academic centers was significantly improved at both 5 and 10 years (59% and 43% survival, respectively) compared with those patients treated at nonacademic centers (51% and 35% survival, respectively; P < .001).

Speculating on factors that might be involved in this discrepancy in survival, the researchers suggested that academic centers might provide increased access to clinical trials, improved physician expertise, as well as improved treatment facilities and supportive care.

“Our results should prompt further investigation in precisely determining the factors that might support this significant effect on decreased survival among those treated in the community and help ameliorate this discrepancy,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Ermann DA et al. Clin Lymphoma Myeloma Leuk. 2020;20(4): e17483.

Academic centers had significantly improved overall survival of patients with diffuse large B-cell lymphoma (DLBCL), according to a large database study.

Nephron/Wikimedia Commons/CC BY-SA 3.0

Researchers used the U.S. National Cancer Database to identify patients with a diagnosis of DLBCL from 2004 to 2015. The researchers identified 27,690 patients for the study. The majority of the patients were white (89.3%) and men (53.7%), with an average age of 64 years. A total of 57.6% of the patients had been treated at nonacademic centers and 42.4% at academic centers, and no notable differences were seen in facility choice among the low- to high-risk International Prognostic Index (IPI) risk categories.

The researchers found that overall survival of the DLBCL patients at academic centers was 108.3 months versus 74.5 months at nonacademic centers (P < .001), according to the study published in Clinical Lymphoma, Myeloma and Leukemia.

In addition, the median survival for patients with high-risk disease treated at academic centers was more than twice that of high-risk patients treated at nonacademic centers (33.5 months vs. 14.4 months, respectively; P < .001). Although the median survival for the other risk categories was also improved, the difference was less pronounced in the groups with lower IPI scores, according to the researchers.

Long-term overall survival for all patients with DLBCL at academic centers was significantly improved at both 5 and 10 years (59% and 43% survival, respectively) compared with those patients treated at nonacademic centers (51% and 35% survival, respectively; P < .001).

Speculating on factors that might be involved in this discrepancy in survival, the researchers suggested that academic centers might provide increased access to clinical trials, improved physician expertise, as well as improved treatment facilities and supportive care.

“Our results should prompt further investigation in precisely determining the factors that might support this significant effect on decreased survival among those treated in the community and help ameliorate this discrepancy,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Ermann DA et al. Clin Lymphoma Myeloma Leuk. 2020;20(4): e17483.

The use of anti-CD22/CD19 CAR-T sequential infusion was shown to have promising efficacy and safety for relapsed/refractory aggressive B-cell lymphoma with GI involvement, according to the results of a small study reported in Cytotherapy.

The open-label, single-center study enrolled 14 patients with relapsed/refractory aggressive B-cell lymphoma involving the GI tract between November 2017 and January 2019. The researchers examined treatment with sequential infusion of anti-CD22 and anti-CD19 CAR T cells in terms of safety and effectiveness.

An objective response was seen in 10 patients, with 7 of these having a complete response. However, 6 of the patients with partial response or stable disease went on to develop progressive disease. In terms of safety, cytokine-release syndrome and GI adverse events were generally mild and manageable, according to the authors. The most serious events were infections: Two of the patients developed bacterial infections in the GI tract, and one of these died of sepsis early after CAR T-cell infusion.

“The [CD22/CD19 CAR T sequential infusion] regimen was generally safe; however, special attention should be paid to the risk of infection in patients with lymphoma involving the GI tract,” the researchers concluded.

The study was funded by the National Science Foundation of China. The authors reported they had no conflicts of interest.

[email protected]

SOURCE: Zheng C et al. Cytotherapy. 2020;22:166-71.

The use of anti-CD22/CD19 CAR-T sequential infusion was shown to have promising efficacy and safety for relapsed/refractory aggressive B-cell lymphoma with GI involvement, according to the results of a small study reported in Cytotherapy.

The open-label, single-center study enrolled 14 patients with relapsed/refractory aggressive B-cell lymphoma involving the GI tract between November 2017 and January 2019. The researchers examined treatment with sequential infusion of anti-CD22 and anti-CD19 CAR T cells in terms of safety and effectiveness.

An objective response was seen in 10 patients, with 7 of these having a complete response. However, 6 of the patients with partial response or stable disease went on to develop progressive disease. In terms of safety, cytokine-release syndrome and GI adverse events were generally mild and manageable, according to the authors. The most serious events were infections: Two of the patients developed bacterial infections in the GI tract, and one of these died of sepsis early after CAR T-cell infusion.

“The [CD22/CD19 CAR T sequential infusion] regimen was generally safe; however, special attention should be paid to the risk of infection in patients with lymphoma involving the GI tract,” the researchers concluded.

The study was funded by the National Science Foundation of China. The authors reported they had no conflicts of interest.

[email protected]

SOURCE: Zheng C et al. Cytotherapy. 2020;22:166-71.

The use of anti-CD22/CD19 CAR-T sequential infusion was shown to have promising efficacy and safety for relapsed/refractory aggressive B-cell lymphoma with GI involvement, according to the results of a small study reported in Cytotherapy.

The open-label, single-center study enrolled 14 patients with relapsed/refractory aggressive B-cell lymphoma involving the GI tract between November 2017 and January 2019. The researchers examined treatment with sequential infusion of anti-CD22 and anti-CD19 CAR T cells in terms of safety and effectiveness.

An objective response was seen in 10 patients, with 7 of these having a complete response. However, 6 of the patients with partial response or stable disease went on to develop progressive disease. In terms of safety, cytokine-release syndrome and GI adverse events were generally mild and manageable, according to the authors. The most serious events were infections: Two of the patients developed bacterial infections in the GI tract, and one of these died of sepsis early after CAR T-cell infusion.

“The [CD22/CD19 CAR T sequential infusion] regimen was generally safe; however, special attention should be paid to the risk of infection in patients with lymphoma involving the GI tract,” the researchers concluded.

The study was funded by the National Science Foundation of China. The authors reported they had no conflicts of interest.

[email protected]

SOURCE: Zheng C et al. Cytotherapy. 2020;22:166-71.