Aggressive Lymphomas

Micrograph showing HL

Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).

The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.

Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.

Brentuximab vedotin is currently not approved as a frontline therapy for HL.

“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.

Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.

Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.

ECHELON-1

ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.

The trial enrolled 1334 patients with histologically confirmed advanced HL.

The primary endpoint is mPFS by independent review facility.

The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.

They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.

Secondary endpoints include overall survival (OS), CR, and safety.

The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).

Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.

The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.

Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.

Febrile neutropenia was reduced with the use of prophylactic growth factors.

Peripheral neuropathy was managed through dose modifications.

Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.

The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.

Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.

Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.

For more on brentuximab vedotin, see the full prescribing informtion. 

Micrograph showing HL

Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).

The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.

Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.

Brentuximab vedotin is currently not approved as a frontline therapy for HL.

“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.

Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.

Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.

ECHELON-1

ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.

The trial enrolled 1334 patients with histologically confirmed advanced HL.

The primary endpoint is mPFS by independent review facility.

The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.

They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.

Secondary endpoints include overall survival (OS), CR, and safety.

The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).

Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.

The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.

Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.

Febrile neutropenia was reduced with the use of prophylactic growth factors.

Peripheral neuropathy was managed through dose modifications.

Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.

The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.

Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.

Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.

For more on brentuximab vedotin, see the full prescribing informtion. 

Micrograph showing HL

Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).

The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.

Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.

Brentuximab vedotin is currently not approved as a frontline therapy for HL.

“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.

Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.

Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.

ECHELON-1

ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.

The trial enrolled 1334 patients with histologically confirmed advanced HL.

The primary endpoint is mPFS by independent review facility.

The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.

They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.

Secondary endpoints include overall survival (OS), CR, and safety.

The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).

Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.

The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.

Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.

Febrile neutropenia was reduced with the use of prophylactic growth factors.

Peripheral neuropathy was managed through dose modifications.

Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.

The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.

Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.

Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.

For more on brentuximab vedotin, see the full prescribing informtion. 

Syringe

The US Food and Drug Administration (FDA) approved a new, subcutaneous (SC) formulation of rituximab with hyaluronidase human (Rituxan Hycela™).

The new formulation includes the same monoclonal antibody as intravenous rituximab, but is combined with an enzyme that helps to deliver rituximab under the skin.

The new treatment reduces administration time from 1.5 hours or more for intravenous rituximab to 5 to 7 minutes for the subcutaneous injection.

It is approved for use in adults with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL).

“[P]eople with 3 of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” said Sandra Horning, MD, chief medical officer of Genentech.

Rituxan Hycela is manufactured by Genentech, Inc, a member of the Roche Group, and jointly marketed by Biogen and Genentech USA, Inc.

“People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important,” she noted.

The FDA based its decision on results from 4 clinical studies:

• SABRINA (NCT01200758): Phase 3 combination study with chemotherapy and maintenance study in previously untreated FL
• SAWYER (NCT01292603): Phase 1b study in previously untreated CLL
• MabEase (NCT01649856): Phase 3 study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase 3 patient preference study in previously untreated FL and DLBCL

This last study showed that 77% of patients preferred subcutaneous over intravenous administration, primarily because it reduced administration time.

Together, these trials represented nearly 2,000 people and demonstrated that subcutaneous administration of rituximab/hyaluronidase resulted in non-inferior levels of rituximab in the blood compared to intravenous rituximab.

And the subcutaneous formulation also demonstrated comparable clinical efficacy outcomes to the intravenous formulation.

Patients must have had at least 1 full dose of intravenous rituximab without severe adverse reactions before receiving the subcutaneous injection. There is a higher risk of certain severe adverse reactions during the first infusion.

The safety profile of rituximab/hyaluronidase is also comparable to intravenous rituximab, except for cutaneous reactions.

The most common (≥20%) adverse reactions observed with rituximab/hyaluronidase were:

• In FL, infections, neutropenia, nausea, constipation, cough, and fatigue.
• In DLBCL, infections, neutropenia, alopecia, nausea, and anemia.
• In CLL, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and erythema at the injection site.

Rituxan Hycela will be available in the US within 1 to 2 weeks, according to the manufacturer. Intravenous rituximab will continue to be available.

A subcutaneous formulation of rituximab (MabThera) had previously been approved for use in European markets by the European Commission.

For further information on the new US formulation, see the full prescribing information. 

Syringe

The US Food and Drug Administration (FDA) approved a new, subcutaneous (SC) formulation of rituximab with hyaluronidase human (Rituxan Hycela™).

The new formulation includes the same monoclonal antibody as intravenous rituximab, but is combined with an enzyme that helps to deliver rituximab under the skin.

The new treatment reduces administration time from 1.5 hours or more for intravenous rituximab to 5 to 7 minutes for the subcutaneous injection.

It is approved for use in adults with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL).

“[P]eople with 3 of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” said Sandra Horning, MD, chief medical officer of Genentech.

Rituxan Hycela is manufactured by Genentech, Inc, a member of the Roche Group, and jointly marketed by Biogen and Genentech USA, Inc.

“People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important,” she noted.

The FDA based its decision on results from 4 clinical studies:

• SABRINA (NCT01200758): Phase 3 combination study with chemotherapy and maintenance study in previously untreated FL
• SAWYER (NCT01292603): Phase 1b study in previously untreated CLL
• MabEase (NCT01649856): Phase 3 study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase 3 patient preference study in previously untreated FL and DLBCL

This last study showed that 77% of patients preferred subcutaneous over intravenous administration, primarily because it reduced administration time.

Together, these trials represented nearly 2,000 people and demonstrated that subcutaneous administration of rituximab/hyaluronidase resulted in non-inferior levels of rituximab in the blood compared to intravenous rituximab.

And the subcutaneous formulation also demonstrated comparable clinical efficacy outcomes to the intravenous formulation.

Patients must have had at least 1 full dose of intravenous rituximab without severe adverse reactions before receiving the subcutaneous injection. There is a higher risk of certain severe adverse reactions during the first infusion.

The safety profile of rituximab/hyaluronidase is also comparable to intravenous rituximab, except for cutaneous reactions.

The most common (≥20%) adverse reactions observed with rituximab/hyaluronidase were:

• In FL, infections, neutropenia, nausea, constipation, cough, and fatigue.
• In DLBCL, infections, neutropenia, alopecia, nausea, and anemia.
• In CLL, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and erythema at the injection site.

Rituxan Hycela will be available in the US within 1 to 2 weeks, according to the manufacturer. Intravenous rituximab will continue to be available.

A subcutaneous formulation of rituximab (MabThera) had previously been approved for use in European markets by the European Commission.

For further information on the new US formulation, see the full prescribing information. 

Syringe

The US Food and Drug Administration (FDA) approved a new, subcutaneous (SC) formulation of rituximab with hyaluronidase human (Rituxan Hycela™).

The new formulation includes the same monoclonal antibody as intravenous rituximab, but is combined with an enzyme that helps to deliver rituximab under the skin.

The new treatment reduces administration time from 1.5 hours or more for intravenous rituximab to 5 to 7 minutes for the subcutaneous injection.

It is approved for use in adults with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL).

“[P]eople with 3 of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” said Sandra Horning, MD, chief medical officer of Genentech.

Rituxan Hycela is manufactured by Genentech, Inc, a member of the Roche Group, and jointly marketed by Biogen and Genentech USA, Inc.

“People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important,” she noted.

The FDA based its decision on results from 4 clinical studies:

• SABRINA (NCT01200758): Phase 3 combination study with chemotherapy and maintenance study in previously untreated FL
• SAWYER (NCT01292603): Phase 1b study in previously untreated CLL
• MabEase (NCT01649856): Phase 3 study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase 3 patient preference study in previously untreated FL and DLBCL

This last study showed that 77% of patients preferred subcutaneous over intravenous administration, primarily because it reduced administration time.

Together, these trials represented nearly 2,000 people and demonstrated that subcutaneous administration of rituximab/hyaluronidase resulted in non-inferior levels of rituximab in the blood compared to intravenous rituximab.

And the subcutaneous formulation also demonstrated comparable clinical efficacy outcomes to the intravenous formulation.

Patients must have had at least 1 full dose of intravenous rituximab without severe adverse reactions before receiving the subcutaneous injection. There is a higher risk of certain severe adverse reactions during the first infusion.

The safety profile of rituximab/hyaluronidase is also comparable to intravenous rituximab, except for cutaneous reactions.

The most common (≥20%) adverse reactions observed with rituximab/hyaluronidase were:

• In FL, infections, neutropenia, nausea, constipation, cough, and fatigue.
• In DLBCL, infections, neutropenia, alopecia, nausea, and anemia.
• In CLL, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and erythema at the injection site.

Rituxan Hycela will be available in the US within 1 to 2 weeks, according to the manufacturer. Intravenous rituximab will continue to be available.

A subcutaneous formulation of rituximab (MabThera) had previously been approved for use in European markets by the European Commission.

For further information on the new US formulation, see the full prescribing information. 

MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.

The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.

MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.

The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.

MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.

The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.” 

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.” 

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.” 

The Food and Drug Administration has approved rituximab plus hyaluronidase human for adult patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).

The combination product, to be marketed as Rituxan Hycela, is administered subcutaneously, shortening administration time to 5 to 7 minutes as compared with the several hours needed for intravenous infusion, the FDA said in a statement.

• Relapsed or refractory FL as a single agent.
• Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
• Nonprogressing (including stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.
• Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone or other anthracycline-based chemotherapy regimens.
• Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide.

The recommended doses are 1,400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1,600 mg rituximab and 26,800 units hyaluronidase human for CLL. The combination treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion, according to the prescribing information.

Rituxan Hycela is marketed by Genentech.

[email protected]

The Food and Drug Administration has approved rituximab plus hyaluronidase human for adult patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).

The combination product, to be marketed as Rituxan Hycela, is administered subcutaneously, shortening administration time to 5 to 7 minutes as compared with the several hours needed for intravenous infusion, the FDA said in a statement.

• Relapsed or refractory FL as a single agent.
• Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
• Nonprogressing (including stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.
• Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone or other anthracycline-based chemotherapy regimens.
• Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide.

The recommended doses are 1,400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1,600 mg rituximab and 26,800 units hyaluronidase human for CLL. The combination treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion, according to the prescribing information.

Rituxan Hycela is marketed by Genentech.

[email protected]

The Food and Drug Administration has approved rituximab plus hyaluronidase human for adult patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).

The combination product, to be marketed as Rituxan Hycela, is administered subcutaneously, shortening administration time to 5 to 7 minutes as compared with the several hours needed for intravenous infusion, the FDA said in a statement.

• Relapsed or refractory FL as a single agent.
• Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
• Nonprogressing (including stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.
• Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone or other anthracycline-based chemotherapy regimens.
• Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide.

The recommended doses are 1,400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1,600 mg rituximab and 26,800 units hyaluronidase human for CLL. The combination treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion, according to the prescribing information.

Rituxan Hycela is marketed by Genentech.

[email protected]

14th International Conference on Malignant Lymphoma (ICML)

LUGANO, SWITZERLAND—Interim results of a phase 2 trial suggest tazemetostat can be effective in patients with heavily pretreated, relapsed or refractory non-Hodgkin lymphoma.

The EZH2 inhibitor produced the highest overall response rate in patients with EZH2-mutated follicular lymphoma (FL), followed by EZH2-mutated diffuse large B-cell lymphoma (DLBCL).

However, the drug also produced complete responses in FL and DLBCL patients with wild-type EZH2.

“If we had focused [only] on patients with EZH2 mutations, we would have missed those other complete responders in the wild-type setting,” said study investigator Franck Morschhauser, MD, PhD, of Centre Hospitalier Régional Universitaire de Lille in France.

He presented results of the trial* during the plenary session of the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by Epizyme, the company developing tazemetostat.

The trial enrolled patients with relapsed or refractory DLBCL or FL who had received at least 2 prior therapies. The patients received tazemetostat at 800 mg twice daily until disease progression or study withdrawal.

Efficacy in FL

Dr Morschhauser presented efficacy data on 67 patients with FL. Thirteen had EZH2 mutations, and 54 had wild-type EZH2. The median age was 62 in the mutated group and 61 in the wild-type group.

Both groups had a median of 4 prior lines of therapy. Fifty-four percent of EZH2-mutated patients were refractory to their last treatment, as were 48% of wild-type patients.

The median time from diagnosis was 7.4 years in mutated patients and 4.9 years in wild-type patients. The median time from last therapy was 13 weeks and 41.3 weeks, respectively.

The overall response rate was 92% (12/13) in EZH2-mutated patients and 26% (14/54) in wild-type patients. The complete response rates were 8% (n=1) and 6% (n=3), respectively.

The median time to first response was 11.9 weeks and 15.2 weeks, respectively.

None of the EZH2-mutated patients have progressed, but 13 (24%) wild-type patients have.

Forty-eight percent of all FL patients remain on study. One EZH2-mutated patient with stable disease is still on study, as are 23 wild-type patients with stable disease.

Efficacy in DLBCL

Dr Morschhauser presented data on 137 patients with DLBCL, 17 with EZH2 mutations and 120 with wild-type EZH2. The median age was 61 in the mutated group and 69 in the wild-type group.

Both groups had a median of 3 prior lines of therapy. Eighty-two percent of EZH2-mutated patients were refractory to their last treatment, as were 63% of wild-type patients.

The median time from diagnosis was 1 year in mutated patients and 2 years in wild-type patients. The median time from last therapy was 8.6 weeks and 11.6 weeks, respectively.

The overall response rate was 29% (5/17) in EZH2-mutated patients and 15% (18/119) in wild-type patients. The complete response rates were 0% (n=0) and 8% (n=10), respectively.

The median time to first response was 8.3 weeks and 8.5 weeks, respectively.

Six (35%) of the EZH2-mutated patients have progressed, as have 60 (50%) wild-type patients.

Twelve percent of all DLBCL patients remain on study. One EZH2-mutated patient with stable disease is still on therapy, as are 4 wild-type patients with stable disease.

Predictors of response

Dr Morschhauser and his colleagues performed next-generation sequencing of samples from 92 patients in an attempt to identify predictors of response to tazemetostat.

The data suggested that EZH2 and MYD88 activating mutations are positive predictors of response, and negative predictors include MYC, TP53, and HIST1H1E.

Safety

Safety data were available for 210 patients. The overall rate of treatment-related adverse events (AEs) was 59%, the rate of grade 3 or higher treatment-related AEs was 18%, and the rate of serious treatment-related AEs was 10%.

There were treatment-related AEs leading to dose interruption (15%), dose reduction (3%), and discontinuation of tazemetostat (2%).

The most common treatment-related AEs were nausea (14%), thrombocytopenia (13%), anemia (10%), neutropenia (9%), diarrhea (8%), asthenia (8%), and fatigue (7%).

Dr Morschhauser said these results “confirm that tazemetostat is quite safe” in this patient population, and enrollment in this trial is ongoing. 

*Data in the abstract differ from the presentation.

14th International Conference on Malignant Lymphoma (ICML)

LUGANO, SWITZERLAND—Interim results of a phase 2 trial suggest tazemetostat can be effective in patients with heavily pretreated, relapsed or refractory non-Hodgkin lymphoma.

The EZH2 inhibitor produced the highest overall response rate in patients with EZH2-mutated follicular lymphoma (FL), followed by EZH2-mutated diffuse large B-cell lymphoma (DLBCL).

However, the drug also produced complete responses in FL and DLBCL patients with wild-type EZH2.

“If we had focused [only] on patients with EZH2 mutations, we would have missed those other complete responders in the wild-type setting,” said study investigator Franck Morschhauser, MD, PhD, of Centre Hospitalier Régional Universitaire de Lille in France.

He presented results of the trial* during the plenary session of the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by Epizyme, the company developing tazemetostat.

The trial enrolled patients with relapsed or refractory DLBCL or FL who had received at least 2 prior therapies. The patients received tazemetostat at 800 mg twice daily until disease progression or study withdrawal.

Efficacy in FL

Dr Morschhauser presented efficacy data on 67 patients with FL. Thirteen had EZH2 mutations, and 54 had wild-type EZH2. The median age was 62 in the mutated group and 61 in the wild-type group.

Both groups had a median of 4 prior lines of therapy. Fifty-four percent of EZH2-mutated patients were refractory to their last treatment, as were 48% of wild-type patients.

The median time from diagnosis was 7.4 years in mutated patients and 4.9 years in wild-type patients. The median time from last therapy was 13 weeks and 41.3 weeks, respectively.

The overall response rate was 92% (12/13) in EZH2-mutated patients and 26% (14/54) in wild-type patients. The complete response rates were 8% (n=1) and 6% (n=3), respectively.

The median time to first response was 11.9 weeks and 15.2 weeks, respectively.

None of the EZH2-mutated patients have progressed, but 13 (24%) wild-type patients have.

Forty-eight percent of all FL patients remain on study. One EZH2-mutated patient with stable disease is still on study, as are 23 wild-type patients with stable disease.

Efficacy in DLBCL

Dr Morschhauser presented data on 137 patients with DLBCL, 17 with EZH2 mutations and 120 with wild-type EZH2. The median age was 61 in the mutated group and 69 in the wild-type group.

Both groups had a median of 3 prior lines of therapy. Eighty-two percent of EZH2-mutated patients were refractory to their last treatment, as were 63% of wild-type patients.

The median time from diagnosis was 1 year in mutated patients and 2 years in wild-type patients. The median time from last therapy was 8.6 weeks and 11.6 weeks, respectively.

The overall response rate was 29% (5/17) in EZH2-mutated patients and 15% (18/119) in wild-type patients. The complete response rates were 0% (n=0) and 8% (n=10), respectively.

The median time to first response was 8.3 weeks and 8.5 weeks, respectively.

Six (35%) of the EZH2-mutated patients have progressed, as have 60 (50%) wild-type patients.

Twelve percent of all DLBCL patients remain on study. One EZH2-mutated patient with stable disease is still on therapy, as are 4 wild-type patients with stable disease.

Predictors of response

Dr Morschhauser and his colleagues performed next-generation sequencing of samples from 92 patients in an attempt to identify predictors of response to tazemetostat.

The data suggested that EZH2 and MYD88 activating mutations are positive predictors of response, and negative predictors include MYC, TP53, and HIST1H1E.

Safety

Safety data were available for 210 patients. The overall rate of treatment-related adverse events (AEs) was 59%, the rate of grade 3 or higher treatment-related AEs was 18%, and the rate of serious treatment-related AEs was 10%.

There were treatment-related AEs leading to dose interruption (15%), dose reduction (3%), and discontinuation of tazemetostat (2%).

The most common treatment-related AEs were nausea (14%), thrombocytopenia (13%), anemia (10%), neutropenia (9%), diarrhea (8%), asthenia (8%), and fatigue (7%).

Dr Morschhauser said these results “confirm that tazemetostat is quite safe” in this patient population, and enrollment in this trial is ongoing. 

*Data in the abstract differ from the presentation.

14th International Conference on Malignant Lymphoma (ICML)

LUGANO, SWITZERLAND—Interim results of a phase 2 trial suggest tazemetostat can be effective in patients with heavily pretreated, relapsed or refractory non-Hodgkin lymphoma.

The EZH2 inhibitor produced the highest overall response rate in patients with EZH2-mutated follicular lymphoma (FL), followed by EZH2-mutated diffuse large B-cell lymphoma (DLBCL).

However, the drug also produced complete responses in FL and DLBCL patients with wild-type EZH2.

“If we had focused [only] on patients with EZH2 mutations, we would have missed those other complete responders in the wild-type setting,” said study investigator Franck Morschhauser, MD, PhD, of Centre Hospitalier Régional Universitaire de Lille in France.

He presented results of the trial* during the plenary session of the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by Epizyme, the company developing tazemetostat.

The trial enrolled patients with relapsed or refractory DLBCL or FL who had received at least 2 prior therapies. The patients received tazemetostat at 800 mg twice daily until disease progression or study withdrawal.

Efficacy in FL

Dr Morschhauser presented efficacy data on 67 patients with FL. Thirteen had EZH2 mutations, and 54 had wild-type EZH2. The median age was 62 in the mutated group and 61 in the wild-type group.

Both groups had a median of 4 prior lines of therapy. Fifty-four percent of EZH2-mutated patients were refractory to their last treatment, as were 48% of wild-type patients.

The median time from diagnosis was 7.4 years in mutated patients and 4.9 years in wild-type patients. The median time from last therapy was 13 weeks and 41.3 weeks, respectively.

The overall response rate was 92% (12/13) in EZH2-mutated patients and 26% (14/54) in wild-type patients. The complete response rates were 8% (n=1) and 6% (n=3), respectively.

The median time to first response was 11.9 weeks and 15.2 weeks, respectively.

None of the EZH2-mutated patients have progressed, but 13 (24%) wild-type patients have.

Forty-eight percent of all FL patients remain on study. One EZH2-mutated patient with stable disease is still on study, as are 23 wild-type patients with stable disease.

Efficacy in DLBCL

Dr Morschhauser presented data on 137 patients with DLBCL, 17 with EZH2 mutations and 120 with wild-type EZH2. The median age was 61 in the mutated group and 69 in the wild-type group.

Both groups had a median of 3 prior lines of therapy. Eighty-two percent of EZH2-mutated patients were refractory to their last treatment, as were 63% of wild-type patients.

The median time from diagnosis was 1 year in mutated patients and 2 years in wild-type patients. The median time from last therapy was 8.6 weeks and 11.6 weeks, respectively.

The overall response rate was 29% (5/17) in EZH2-mutated patients and 15% (18/119) in wild-type patients. The complete response rates were 0% (n=0) and 8% (n=10), respectively.

The median time to first response was 8.3 weeks and 8.5 weeks, respectively.

Six (35%) of the EZH2-mutated patients have progressed, as have 60 (50%) wild-type patients.

Twelve percent of all DLBCL patients remain on study. One EZH2-mutated patient with stable disease is still on therapy, as are 4 wild-type patients with stable disease.

Predictors of response

Dr Morschhauser and his colleagues performed next-generation sequencing of samples from 92 patients in an attempt to identify predictors of response to tazemetostat.

The data suggested that EZH2 and MYD88 activating mutations are positive predictors of response, and negative predictors include MYC, TP53, and HIST1H1E.

Safety

Safety data were available for 210 patients. The overall rate of treatment-related adverse events (AEs) was 59%, the rate of grade 3 or higher treatment-related AEs was 18%, and the rate of serious treatment-related AEs was 10%.

There were treatment-related AEs leading to dose interruption (15%), dose reduction (3%), and discontinuation of tazemetostat (2%).

The most common treatment-related AEs were nausea (14%), thrombocytopenia (13%), anemia (10%), neutropenia (9%), diarrhea (8%), asthenia (8%), and fatigue (7%).

Dr Morschhauser said these results “confirm that tazemetostat is quite safe” in this patient population, and enrollment in this trial is ongoing. 

*Data in the abstract differ from the presentation.

Anna Sureda, MD, PhD

In this editorial, Anna Sureda, MD, PhD, details the need for new frontline treatments for patients with Hodgkin lymphoma, including those with advanced stage disease.

 Dr Sureda is head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme at the Institut Català d'Oncologia, Hospital Duran i Reynals, in Barcelona, Spain. She has received consultancy fees from Takeda/Millennium Pharmaceuticals, Merck Sharp & Dohme, and Bristol-Myers Squibb.

Hodgkin lymphoma has traditionally been known as a cancer with generally favorable outcomes. Yet, as with any cancer treatment, there is always room for improvement. For Hodgkin lymphoma specifically, there remains a significant unmet need in the frontline setting for patients with advanced disease (Stage III or Stage IV).

Hodgkin lymphoma most commonly affects young adults as well as adults over the age of 55.¹ Both age at diagnosis and stage of the disease are significant factors that must be considered when determining treatment plans, as they can affect a patient’s success in achieving long-term remission.

Though early stage patients have demonstrated 5-year survival rates of approximately 90%, this number drops to 70% in patients with advanced stage disease,^2-4 underlining the challenges of treating later stage Hodgkin lymphoma.

Additionally, only 50% of patients with relapsed or refractory disease will experience long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT)^5-6— a historically and frequently used treatment regimen.

These facts support the importance of successful frontline treatment and highlight a gap with current treatment regimens.^7-10

With current frontline Hodgkin lymphoma treatments, it can be a challenge for physicians to balance efficacy with safety. While allowing the patient to achieve long-term remission remains the goal, physicians are also considering the impact of treatment-related side effects including endocrine dysfunction, cardiac dysfunction, lung toxicity, infertility, and an increased risk of secondary cancers when determining the best possible treatment.^8-15

Advanced stage vs early stage Hodgkin lymphoma

Stage of disease at diagnosis has a large influence on outcomes, with advanced stage patients having poorer outcomes than earlier stage patients.^7,15-16 Advanced Hodgkin lymphoma patients are more likely to progress or relapse,^7,15-16 with nearly one third remaining uncured following standard frontline therapy.^7-10

As seen in Figure 1 below, there is a clear difference in progression-free survival for early versus advanced stage Hodgkin lymphoma.¹⁶

The difference between early stage and advanced stage patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) demonstrates the heightened importance of successful frontline treatment for those with advanced stage disease.¹⁶

 Unmet needs with current frontline Hodgkin lymphoma treatment

 Though current treatments for frontline Hodgkin lymphoma, including ABVD and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), have improved outcomes for patients, these standard regimens are more than 20 years old.

ABVD is generally regarded as the treatment of choice based on its efficacy, relative ease of administration, and side effect profile.¹⁷

Escalated BEACOPP, on the other hand, was developed to improve outcomes for advanced stage patients but is associated with increased toxicity.^8-10,13,18

Positron emission tomography (PET) scans have also been identified as a pathway to help guide further treatment, but patients with advanced stage Hodgkin lymphoma may relapse more often, despite a negative interim PET scan, compared to stage II patients.¹⁹

Among current treatments, side effects including lung and cardiotoxicity as well as an increased risk of secondary cancers are a concern for both physicians and their patients.^8-10,13-15

 Similarly, radiation therapy, often used in conjunction with chemotherapy for patients who have a large tumor burden in one part of the body, usually the chest,²⁰ is also associated with an increased risk of secondary cancers and cardiotoxicity.^8-10,21

With these complications in mind, stabilizing the effects between improved efficacy and minimizing the toxicities associated with current frontline treatments needs to be a focus as new therapies are developed.

For young patients specifically, minimizing toxicities is crucial, as many will have a lifetime ahead of them after Hodgkin lymphoma and will want to avoid the risks associated with current treatments including lung disease, heart disease and infertility.^{8-10,12-15,22}

Treating elderly patients can also be challenging due to their reduced ability to tolerate aggressive frontline treatment and multi-agent chemotherapy, which causes inferior survival outcomes when compared to younger patients.^23-25 These secondary effects can affect a patient’s quality of life^{8-9,12,14-15,22,26-28}  and exacerbate preexisting conditions commonly experienced by those undergoing treatment, including long-term fatigue, chronic medical and psychosocial complications, and general deterioration in physical well-being.²²

Studies have shown that most relapses after ASCT typically occur within 2 years.²⁹ After a relapse, the patient may endure a substantial physical and psychological burden due to the need for additional treatment, impacting quality of life for both the patient and their caregiver.^22,26,30

 Goals of clinical research

Despite its recognition as a highly treatable cancer, newly diagnosed Hodgkin lymphoma remains incurable in up to 30% of patients with advanced disease.^7-10 Though current therapies seek to achieve remission and extend the lives of patients, it is often at the cost of treatment-related toxicities and side effects that can significantly reduce quality of life.

Moving forward, it is critical that these gaps in treatment are addressed in new frontline treatments that aim to benefit patients, including those with advanced stage disease, while reducing short-term and long-term toxicities. 

 Acknowledgements: The author would like to acknowledge the W2O Group for their writing support, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

______________________________________________________

¹American Cancer Society. What Are the Key Statistics About Hodgkin Disease? https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed February 16, 2017.

²Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.

³American Cancer Society. Survival Rates for Hodgkin Disease by Stage. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed February 16, 2017.

⁴Fermé C, et al. New Engl J Med, 2007.357:1916–27.

⁵Sureda A, et al. Ann Oncol, 2005;16: 625–633.

⁶Majhail NS, et al. Biol Blood Marrow Transplant, 2006;12:1065–1072.

⁷Gordon LI, et al. J Clin Oncol, 2013;31:684-691.

⁸Carde P, et al. J Clin Oncol, 2016;34(17):2028-2036.

⁹Engert A, et al. J Clin Oncol, 2009;27(27):4548-4554

¹⁰Viviani S, et al. New Engl J Med, 2011;365(3):203-212.

¹¹Sklar C, et al. J Endocrinology & Metabolism, 2000;85(9):3227-3232

¹²Behringer K, et al. J Clin Oncol, 2013;31:231-239.

¹³Borchmann P, et al. J Clin Oncol, 2011;29(32):4234-4242.

¹⁴Duggan DB, et al. J Clin Oncol, 2003;21(4):607-614.

¹⁵Johnson P, McKenzie H. Blood, 2015;125(11):1717-1723.

¹⁶Maddi RN, et al. Indian J Medical and Paediatric Oncology, 2015;36(4):255-260

¹⁷Ansell SM. American Journal of Hematology, 2014;89: 771–779.

¹⁸Merli F, et al. J Clin Oncol, 34:1175-1181.

¹⁹Johnson P, et al. N Engl J Med. 2016;3‌74:24‌19‑24‌29

²⁰American Cancer Society. Treating Hodgkin Disease: Radiation Therapy for Hodgkin Disease. https://www.cancer.org/cancer/hodgkin-lymphoma/treating/radiation.html. Accessed January 30, 2017.

²¹Adams MJ, et al. J Clin Oncol, 2004; 22: 3139–48.

²²Khimani N, et al. Ann Oncol, 2013;24(1):226-230.

²³Engert A, et al. J Clin Oncol, 2005;23(22):5052-60.

²⁴Evens AM, et al. Br J Haematol, 2013;161: 76–86.

²⁵Janssen-Heijnen ML, et al. Br J Haematol, 2005;129:597-606.

²⁶Ganz PA et al. J Clin Oncol, 2003;21(18):3512-3519.

²⁷Daniels LA, et al. Br J Cancer 2014;110:868-874.

²⁸Loge JH, et al. Ann Oncol. 1999;10:71-77.

²⁹Brusamolino E, Carella AM. Haematologica, 2007;92:6-10

³⁰Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat? Personalized Medicine in Oncology, 2016. http://www.personalizedmedonc.com/article/consolidation-therapy-after-asct-in-hodgkin-lymphoma-why-and-who-to-treat/. Accessed February 16, 2017.

Anna Sureda, MD, PhD

In this editorial, Anna Sureda, MD, PhD, details the need for new frontline treatments for patients with Hodgkin lymphoma, including those with advanced stage disease.

 Dr Sureda is head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme at the Institut Català d'Oncologia, Hospital Duran i Reynals, in Barcelona, Spain. She has received consultancy fees from Takeda/Millennium Pharmaceuticals, Merck Sharp & Dohme, and Bristol-Myers Squibb.

Hodgkin lymphoma has traditionally been known as a cancer with generally favorable outcomes. Yet, as with any cancer treatment, there is always room for improvement. For Hodgkin lymphoma specifically, there remains a significant unmet need in the frontline setting for patients with advanced disease (Stage III or Stage IV).

Hodgkin lymphoma most commonly affects young adults as well as adults over the age of 55.¹ Both age at diagnosis and stage of the disease are significant factors that must be considered when determining treatment plans, as they can affect a patient’s success in achieving long-term remission.

Though early stage patients have demonstrated 5-year survival rates of approximately 90%, this number drops to 70% in patients with advanced stage disease,^2-4 underlining the challenges of treating later stage Hodgkin lymphoma.

Additionally, only 50% of patients with relapsed or refractory disease will experience long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT)^5-6— a historically and frequently used treatment regimen.

These facts support the importance of successful frontline treatment and highlight a gap with current treatment regimens.^7-10

With current frontline Hodgkin lymphoma treatments, it can be a challenge for physicians to balance efficacy with safety. While allowing the patient to achieve long-term remission remains the goal, physicians are also considering the impact of treatment-related side effects including endocrine dysfunction, cardiac dysfunction, lung toxicity, infertility, and an increased risk of secondary cancers when determining the best possible treatment.^8-15

Advanced stage vs early stage Hodgkin lymphoma

Stage of disease at diagnosis has a large influence on outcomes, with advanced stage patients having poorer outcomes than earlier stage patients.^7,15-16 Advanced Hodgkin lymphoma patients are more likely to progress or relapse,^7,15-16 with nearly one third remaining uncured following standard frontline therapy.^7-10

As seen in Figure 1 below, there is a clear difference in progression-free survival for early versus advanced stage Hodgkin lymphoma.¹⁶

The difference between early stage and advanced stage patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) demonstrates the heightened importance of successful frontline treatment for those with advanced stage disease.¹⁶

 Unmet needs with current frontline Hodgkin lymphoma treatment

 Though current treatments for frontline Hodgkin lymphoma, including ABVD and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), have improved outcomes for patients, these standard regimens are more than 20 years old.

ABVD is generally regarded as the treatment of choice based on its efficacy, relative ease of administration, and side effect profile.¹⁷

Escalated BEACOPP, on the other hand, was developed to improve outcomes for advanced stage patients but is associated with increased toxicity.^8-10,13,18

Positron emission tomography (PET) scans have also been identified as a pathway to help guide further treatment, but patients with advanced stage Hodgkin lymphoma may relapse more often, despite a negative interim PET scan, compared to stage II patients.¹⁹

Among current treatments, side effects including lung and cardiotoxicity as well as an increased risk of secondary cancers are a concern for both physicians and their patients.^8-10,13-15

 Similarly, radiation therapy, often used in conjunction with chemotherapy for patients who have a large tumor burden in one part of the body, usually the chest,²⁰ is also associated with an increased risk of secondary cancers and cardiotoxicity.^8-10,21

With these complications in mind, stabilizing the effects between improved efficacy and minimizing the toxicities associated with current frontline treatments needs to be a focus as new therapies are developed.

For young patients specifically, minimizing toxicities is crucial, as many will have a lifetime ahead of them after Hodgkin lymphoma and will want to avoid the risks associated with current treatments including lung disease, heart disease and infertility.^{8-10,12-15,22}

Treating elderly patients can also be challenging due to their reduced ability to tolerate aggressive frontline treatment and multi-agent chemotherapy, which causes inferior survival outcomes when compared to younger patients.^23-25 These secondary effects can affect a patient’s quality of life^{8-9,12,14-15,22,26-28}  and exacerbate preexisting conditions commonly experienced by those undergoing treatment, including long-term fatigue, chronic medical and psychosocial complications, and general deterioration in physical well-being.²²

Studies have shown that most relapses after ASCT typically occur within 2 years.²⁹ After a relapse, the patient may endure a substantial physical and psychological burden due to the need for additional treatment, impacting quality of life for both the patient and their caregiver.^22,26,30

 Goals of clinical research

Despite its recognition as a highly treatable cancer, newly diagnosed Hodgkin lymphoma remains incurable in up to 30% of patients with advanced disease.^7-10 Though current therapies seek to achieve remission and extend the lives of patients, it is often at the cost of treatment-related toxicities and side effects that can significantly reduce quality of life.

Moving forward, it is critical that these gaps in treatment are addressed in new frontline treatments that aim to benefit patients, including those with advanced stage disease, while reducing short-term and long-term toxicities. 

 Acknowledgements: The author would like to acknowledge the W2O Group for their writing support, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

______________________________________________________

¹American Cancer Society. What Are the Key Statistics About Hodgkin Disease? https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed February 16, 2017.

²Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.

³American Cancer Society. Survival Rates for Hodgkin Disease by Stage. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed February 16, 2017.

⁴Fermé C, et al. New Engl J Med, 2007.357:1916–27.

⁵Sureda A, et al. Ann Oncol, 2005;16: 625–633.

⁶Majhail NS, et al. Biol Blood Marrow Transplant, 2006;12:1065–1072.

⁷Gordon LI, et al. J Clin Oncol, 2013;31:684-691.

⁸Carde P, et al. J Clin Oncol, 2016;34(17):2028-2036.

⁹Engert A, et al. J Clin Oncol, 2009;27(27):4548-4554

¹⁰Viviani S, et al. New Engl J Med, 2011;365(3):203-212.

¹¹Sklar C, et al. J Endocrinology & Metabolism, 2000;85(9):3227-3232

¹²Behringer K, et al. J Clin Oncol, 2013;31:231-239.

¹³Borchmann P, et al. J Clin Oncol, 2011;29(32):4234-4242.

¹⁴Duggan DB, et al. J Clin Oncol, 2003;21(4):607-614.

¹⁵Johnson P, McKenzie H. Blood, 2015;125(11):1717-1723.

¹⁶Maddi RN, et al. Indian J Medical and Paediatric Oncology, 2015;36(4):255-260

¹⁷Ansell SM. American Journal of Hematology, 2014;89: 771–779.

¹⁸Merli F, et al. J Clin Oncol, 34:1175-1181.

¹⁹Johnson P, et al. N Engl J Med. 2016;3‌74:24‌19‑24‌29

²⁰American Cancer Society. Treating Hodgkin Disease: Radiation Therapy for Hodgkin Disease. https://www.cancer.org/cancer/hodgkin-lymphoma/treating/radiation.html. Accessed January 30, 2017.

²¹Adams MJ, et al. J Clin Oncol, 2004; 22: 3139–48.

²²Khimani N, et al. Ann Oncol, 2013;24(1):226-230.

²³Engert A, et al. J Clin Oncol, 2005;23(22):5052-60.

²⁴Evens AM, et al. Br J Haematol, 2013;161: 76–86.

²⁵Janssen-Heijnen ML, et al. Br J Haematol, 2005;129:597-606.

²⁶Ganz PA et al. J Clin Oncol, 2003;21(18):3512-3519.

²⁷Daniels LA, et al. Br J Cancer 2014;110:868-874.

²⁸Loge JH, et al. Ann Oncol. 1999;10:71-77.

²⁹Brusamolino E, Carella AM. Haematologica, 2007;92:6-10

³⁰Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat? Personalized Medicine in Oncology, 2016. http://www.personalizedmedonc.com/article/consolidation-therapy-after-asct-in-hodgkin-lymphoma-why-and-who-to-treat/. Accessed February 16, 2017.

Anna Sureda, MD, PhD

In this editorial, Anna Sureda, MD, PhD, details the need for new frontline treatments for patients with Hodgkin lymphoma, including those with advanced stage disease.

 Dr Sureda is head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme at the Institut Català d'Oncologia, Hospital Duran i Reynals, in Barcelona, Spain. She has received consultancy fees from Takeda/Millennium Pharmaceuticals, Merck Sharp & Dohme, and Bristol-Myers Squibb.

Hodgkin lymphoma has traditionally been known as a cancer with generally favorable outcomes. Yet, as with any cancer treatment, there is always room for improvement. For Hodgkin lymphoma specifically, there remains a significant unmet need in the frontline setting for patients with advanced disease (Stage III or Stage IV).

Hodgkin lymphoma most commonly affects young adults as well as adults over the age of 55.¹ Both age at diagnosis and stage of the disease are significant factors that must be considered when determining treatment plans, as they can affect a patient’s success in achieving long-term remission.

Though early stage patients have demonstrated 5-year survival rates of approximately 90%, this number drops to 70% in patients with advanced stage disease,^2-4 underlining the challenges of treating later stage Hodgkin lymphoma.

Additionally, only 50% of patients with relapsed or refractory disease will experience long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT)^5-6— a historically and frequently used treatment regimen.

These facts support the importance of successful frontline treatment and highlight a gap with current treatment regimens.^7-10

With current frontline Hodgkin lymphoma treatments, it can be a challenge for physicians to balance efficacy with safety. While allowing the patient to achieve long-term remission remains the goal, physicians are also considering the impact of treatment-related side effects including endocrine dysfunction, cardiac dysfunction, lung toxicity, infertility, and an increased risk of secondary cancers when determining the best possible treatment.^8-15

Advanced stage vs early stage Hodgkin lymphoma

Stage of disease at diagnosis has a large influence on outcomes, with advanced stage patients having poorer outcomes than earlier stage patients.^7,15-16 Advanced Hodgkin lymphoma patients are more likely to progress or relapse,^7,15-16 with nearly one third remaining uncured following standard frontline therapy.^7-10

As seen in Figure 1 below, there is a clear difference in progression-free survival for early versus advanced stage Hodgkin lymphoma.¹⁶

The difference between early stage and advanced stage patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) demonstrates the heightened importance of successful frontline treatment for those with advanced stage disease.¹⁶

 Unmet needs with current frontline Hodgkin lymphoma treatment

 Though current treatments for frontline Hodgkin lymphoma, including ABVD and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), have improved outcomes for patients, these standard regimens are more than 20 years old.

ABVD is generally regarded as the treatment of choice based on its efficacy, relative ease of administration, and side effect profile.¹⁷

Escalated BEACOPP, on the other hand, was developed to improve outcomes for advanced stage patients but is associated with increased toxicity.^8-10,13,18

Positron emission tomography (PET) scans have also been identified as a pathway to help guide further treatment, but patients with advanced stage Hodgkin lymphoma may relapse more often, despite a negative interim PET scan, compared to stage II patients.¹⁹

Among current treatments, side effects including lung and cardiotoxicity as well as an increased risk of secondary cancers are a concern for both physicians and their patients.^8-10,13-15

 Similarly, radiation therapy, often used in conjunction with chemotherapy for patients who have a large tumor burden in one part of the body, usually the chest,²⁰ is also associated with an increased risk of secondary cancers and cardiotoxicity.^8-10,21

With these complications in mind, stabilizing the effects between improved efficacy and minimizing the toxicities associated with current frontline treatments needs to be a focus as new therapies are developed.

For young patients specifically, minimizing toxicities is crucial, as many will have a lifetime ahead of them after Hodgkin lymphoma and will want to avoid the risks associated with current treatments including lung disease, heart disease and infertility.^{8-10,12-15,22}

Treating elderly patients can also be challenging due to their reduced ability to tolerate aggressive frontline treatment and multi-agent chemotherapy, which causes inferior survival outcomes when compared to younger patients.^23-25 These secondary effects can affect a patient’s quality of life^{8-9,12,14-15,22,26-28}  and exacerbate preexisting conditions commonly experienced by those undergoing treatment, including long-term fatigue, chronic medical and psychosocial complications, and general deterioration in physical well-being.²²

Studies have shown that most relapses after ASCT typically occur within 2 years.²⁹ After a relapse, the patient may endure a substantial physical and psychological burden due to the need for additional treatment, impacting quality of life for both the patient and their caregiver.^22,26,30

 Goals of clinical research

Despite its recognition as a highly treatable cancer, newly diagnosed Hodgkin lymphoma remains incurable in up to 30% of patients with advanced disease.^7-10 Though current therapies seek to achieve remission and extend the lives of patients, it is often at the cost of treatment-related toxicities and side effects that can significantly reduce quality of life.

Moving forward, it is critical that these gaps in treatment are addressed in new frontline treatments that aim to benefit patients, including those with advanced stage disease, while reducing short-term and long-term toxicities. 

 Acknowledgements: The author would like to acknowledge the W2O Group for their writing support, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

______________________________________________________

¹American Cancer Society. What Are the Key Statistics About Hodgkin Disease? https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed February 16, 2017.

²Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.

³American Cancer Society. Survival Rates for Hodgkin Disease by Stage. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed February 16, 2017.

⁴Fermé C, et al. New Engl J Med, 2007.357:1916–27.

⁵Sureda A, et al. Ann Oncol, 2005;16: 625–633.

⁶Majhail NS, et al. Biol Blood Marrow Transplant, 2006;12:1065–1072.

⁷Gordon LI, et al. J Clin Oncol, 2013;31:684-691.

⁸Carde P, et al. J Clin Oncol, 2016;34(17):2028-2036.

⁹Engert A, et al. J Clin Oncol, 2009;27(27):4548-4554

¹⁰Viviani S, et al. New Engl J Med, 2011;365(3):203-212.

¹¹Sklar C, et al. J Endocrinology & Metabolism, 2000;85(9):3227-3232

¹²Behringer K, et al. J Clin Oncol, 2013;31:231-239.

¹³Borchmann P, et al. J Clin Oncol, 2011;29(32):4234-4242.

¹⁴Duggan DB, et al. J Clin Oncol, 2003;21(4):607-614.

¹⁵Johnson P, McKenzie H. Blood, 2015;125(11):1717-1723.

¹⁶Maddi RN, et al. Indian J Medical and Paediatric Oncology, 2015;36(4):255-260

¹⁷Ansell SM. American Journal of Hematology, 2014;89: 771–779.

¹⁸Merli F, et al. J Clin Oncol, 34:1175-1181.

¹⁹Johnson P, et al. N Engl J Med. 2016;3‌74:24‌19‑24‌29

²⁰American Cancer Society. Treating Hodgkin Disease: Radiation Therapy for Hodgkin Disease. https://www.cancer.org/cancer/hodgkin-lymphoma/treating/radiation.html. Accessed January 30, 2017.

²¹Adams MJ, et al. J Clin Oncol, 2004; 22: 3139–48.

²²Khimani N, et al. Ann Oncol, 2013;24(1):226-230.

²³Engert A, et al. J Clin Oncol, 2005;23(22):5052-60.

²⁴Evens AM, et al. Br J Haematol, 2013;161: 76–86.

²⁵Janssen-Heijnen ML, et al. Br J Haematol, 2005;129:597-606.

²⁶Ganz PA et al. J Clin Oncol, 2003;21(18):3512-3519.

²⁷Daniels LA, et al. Br J Cancer 2014;110:868-874.

²⁸Loge JH, et al. Ann Oncol. 1999;10:71-77.

²⁹Brusamolino E, Carella AM. Haematologica, 2007;92:6-10

³⁰Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat? Personalized Medicine in Oncology, 2016. http://www.personalizedmedonc.com/article/consolidation-therapy-after-asct-in-hodgkin-lymphoma-why-and-who-to-treat/. Accessed February 16, 2017.

LUGANO, SWITZERLAND – Combining lenalidomide (Revlimid) with an anti-CD19 monoclonal antibody labeled MOR208 showed promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for stem cell transplant and had poor prognosis, early interim results from a clinical study indicate.

Among 34 patients evaluable for response, the preliminary objective response rate (ORR) was 56%, including complete responses in 32% of patients, reported Gilles Salles, MD, PhD, of the University of Lyon, France.

[email protected]

LUGANO, SWITZERLAND – Combining lenalidomide (Revlimid) with an anti-CD19 monoclonal antibody labeled MOR208 showed promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for stem cell transplant and had poor prognosis, early interim results from a clinical study indicate.

Among 34 patients evaluable for response, the preliminary objective response rate (ORR) was 56%, including complete responses in 32% of patients, reported Gilles Salles, MD, PhD, of the University of Lyon, France.

[email protected]

LUGANO, SWITZERLAND – Combining lenalidomide (Revlimid) with an anti-CD19 monoclonal antibody labeled MOR208 showed promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for stem cell transplant and had poor prognosis, early interim results from a clinical study indicate.

Among 34 patients evaluable for response, the preliminary objective response rate (ORR) was 56%, including complete responses in 32% of patients, reported Gilles Salles, MD, PhD, of the University of Lyon, France.

[email protected]

Photo by Linda Bartlett

The European Commission (EC) has approved the Sandoz biosimilar rituximab (Rixathon^®) for use in the European Economic Area.

Rixathon is approved for all indications of the reference medicine, MabThera®, including follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and immunologic diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

This approval allows Rixathon to be marketed in the member states of the European Union and Iceland, Liechtenstein, and Norway, members of the European Free Trade Association.

The approval “represents a big win for patients in Europe with blood cancers or immunological diseases,” according to Carol Lynch, global head of Biopharmaceuticals at Sandoz.

“Rixathon will be one of the 5 major launches we plan in the next 4 years,” she said.

Earlier in the year, the European Medicines Agency’s Committee for Medicinal Products for Human Use had recommended marketing authorization for Rixathon.

The EC based its approval on a comprehensive development program generating analytical, preclinical, and clinical data.  Clinical studies included ASSIST-RA and ASSIST-FL.

ASSIST-RA demonstrated that the biosimilar product has equivalent pharmacokinetic and pharmacodynamic profiles to the reference medicine, with no clinically meaningful differences in safety, tolerability, or immunogenicity in patients with rheumatoid arthritis.

ASSIST-FL was a phase 3 study confirming efficacy and safety. The study met its primary endpoint of equivalence in overall response rate between the biosimilar product and the reference medicine after 6 months.

ASSIST-FL also confirmed the comparable safety profiles of the 2 medicines.

Sandoz is a division of the Swiss pharmaceutical company Novartis. MabThera is a registered trademark of F. Hoffmann-La-Roche AG.

Another Sandoz biosimilar rituximab has been approved in the EU as Riximyo® under a duplicate marketing authorization. 

Photo by Linda Bartlett

The European Commission (EC) has approved the Sandoz biosimilar rituximab (Rixathon^®) for use in the European Economic Area.

Rixathon is approved for all indications of the reference medicine, MabThera®, including follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and immunologic diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

This approval allows Rixathon to be marketed in the member states of the European Union and Iceland, Liechtenstein, and Norway, members of the European Free Trade Association.

The approval “represents a big win for patients in Europe with blood cancers or immunological diseases,” according to Carol Lynch, global head of Biopharmaceuticals at Sandoz.

“Rixathon will be one of the 5 major launches we plan in the next 4 years,” she said.

Earlier in the year, the European Medicines Agency’s Committee for Medicinal Products for Human Use had recommended marketing authorization for Rixathon.

The EC based its approval on a comprehensive development program generating analytical, preclinical, and clinical data.  Clinical studies included ASSIST-RA and ASSIST-FL.

ASSIST-RA demonstrated that the biosimilar product has equivalent pharmacokinetic and pharmacodynamic profiles to the reference medicine, with no clinically meaningful differences in safety, tolerability, or immunogenicity in patients with rheumatoid arthritis.

ASSIST-FL was a phase 3 study confirming efficacy and safety. The study met its primary endpoint of equivalence in overall response rate between the biosimilar product and the reference medicine after 6 months.

ASSIST-FL also confirmed the comparable safety profiles of the 2 medicines.

Sandoz is a division of the Swiss pharmaceutical company Novartis. MabThera is a registered trademark of F. Hoffmann-La-Roche AG.

Another Sandoz biosimilar rituximab has been approved in the EU as Riximyo® under a duplicate marketing authorization. 

Photo by Linda Bartlett

The European Commission (EC) has approved the Sandoz biosimilar rituximab (Rixathon^®) for use in the European Economic Area.

Rixathon is approved for all indications of the reference medicine, MabThera®, including follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and immunologic diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

This approval allows Rixathon to be marketed in the member states of the European Union and Iceland, Liechtenstein, and Norway, members of the European Free Trade Association.

The approval “represents a big win for patients in Europe with blood cancers or immunological diseases,” according to Carol Lynch, global head of Biopharmaceuticals at Sandoz.

“Rixathon will be one of the 5 major launches we plan in the next 4 years,” she said.

Earlier in the year, the European Medicines Agency’s Committee for Medicinal Products for Human Use had recommended marketing authorization for Rixathon.

The EC based its approval on a comprehensive development program generating analytical, preclinical, and clinical data.  Clinical studies included ASSIST-RA and ASSIST-FL.

ASSIST-RA demonstrated that the biosimilar product has equivalent pharmacokinetic and pharmacodynamic profiles to the reference medicine, with no clinically meaningful differences in safety, tolerability, or immunogenicity in patients with rheumatoid arthritis.

ASSIST-FL was a phase 3 study confirming efficacy and safety. The study met its primary endpoint of equivalence in overall response rate between the biosimilar product and the reference medicine after 6 months.

ASSIST-FL also confirmed the comparable safety profiles of the 2 medicines.

Sandoz is a division of the Swiss pharmaceutical company Novartis. MabThera is a registered trademark of F. Hoffmann-La-Roche AG.

Another Sandoz biosimilar rituximab has been approved in the EU as Riximyo® under a duplicate marketing authorization. 

Photo © ASCO/David Eulitt 2017

CHICAGO—Chimeric antigen receptor (CAR) T cells combined with ibrutinib enhance T-cell function and can induce complete remission (CR) in patients with chronic lymphocytic leukemia (CLL), researchers report.

Many CLL patients receive ibrutinib treatment, which is well tolerated, but few patients achieve CR.

Immunotherapy with anti-CD19 CAR T cells has induced CR in 25% - 45% of patients with CLL, Saar Gill, MD, of the University of Pennsylvania in Philadelphia, told Hematology Times, and these CRs tend to be durable.

So investigators conducted a pilot trial in 10 patients to test whether combining anti-CD19 CAR T cells with ibrutinib would enhance the CR rate.

Dr Gill reported the findings of the pilot trial at the ASCO 2017 Annual Meeting (abstract 7509).

The patients must have failed at least 1 regimen before ibrutinib, unless they had del(17)(p13.1) or a TP53 mutation.

T cells were lentivirally transduced to express a CAR that included humanized anti-CD19.

Patients were lymphodepleted 1 week before infusion, and ibrutinib was continued throughout the trial.

After a median follow-up of 6 months, 8 of the 9 evaluable patients show absence of CLL in the bone marrow by flow cytometry or minimal residual disease (MRD) negative, and all remain in marrow CR at last follow-up, Dr Gill said.

Radiologic responses are less clear-cut and may require longer follow-up.

“All but 1 patient achieved MRD with deep sequencing. We have deep response in the bone marrow,” Dr Gill said. He also noted that the treatment was well tolerated.

Cytokine release syndrome (CRS) developed in 9 patients: grade 1 in 2 patients, grade 2 in 6 patients, and grade 3 in 1 patient. One patient developed grade 4 tumor lysis syndrome. Treatment of CRS with the IL-6 receptor antagonist tocilizumab was not required.

There was modest residual splenomegaly in 3 of 5 patients, and adenopathy resolved in 4 of 6 patients, with progression in 1 patient.

Ibrutinib reduced CRS apparently by blocking cytokine production by T cells, said Dr Gill, adding, “The combination led to improved efficacy without increased toxicity.”

Ibrutinib may make CAR T-cell therapy more feasible.

Patients who receive ibrutinib for 6 months have a better T-cell response.

“This opens up future discussions of bringing CAR T-cell therapy earlier into CLL treatment,” said Dr Gill.

He envisions patients receiving ibrutinib for 6 months, which would allow time to manufacture T cells, and then have a T-cell infusion.

“Once patients achieve MRD, then we can discuss the possibility of stopping ibrutinib therapy,” he said.

“Most patients remain on ibrutinib, but longer follow-up may show whether remissions are sustained off ibrutinib.”

The researchers have ongoing plans to treat 25 patients with CTL19 plus ibrutinib in a continuation of this trial.

Dr Gill said longer follow-up will reveal the durability of these results “and could support evaluation of a first-line combination approach in an attempt to obviate the need for chronic therapy.” 

Photo © ASCO/David Eulitt 2017

CHICAGO—Chimeric antigen receptor (CAR) T cells combined with ibrutinib enhance T-cell function and can induce complete remission (CR) in patients with chronic lymphocytic leukemia (CLL), researchers report.

Many CLL patients receive ibrutinib treatment, which is well tolerated, but few patients achieve CR.

Immunotherapy with anti-CD19 CAR T cells has induced CR in 25% - 45% of patients with CLL, Saar Gill, MD, of the University of Pennsylvania in Philadelphia, told Hematology Times, and these CRs tend to be durable.

So investigators conducted a pilot trial in 10 patients to test whether combining anti-CD19 CAR T cells with ibrutinib would enhance the CR rate.

Dr Gill reported the findings of the pilot trial at the ASCO 2017 Annual Meeting (abstract 7509).

The patients must have failed at least 1 regimen before ibrutinib, unless they had del(17)(p13.1) or a TP53 mutation.

T cells were lentivirally transduced to express a CAR that included humanized anti-CD19.

Patients were lymphodepleted 1 week before infusion, and ibrutinib was continued throughout the trial.

After a median follow-up of 6 months, 8 of the 9 evaluable patients show absence of CLL in the bone marrow by flow cytometry or minimal residual disease (MRD) negative, and all remain in marrow CR at last follow-up, Dr Gill said.

Radiologic responses are less clear-cut and may require longer follow-up.

“All but 1 patient achieved MRD with deep sequencing. We have deep response in the bone marrow,” Dr Gill said. He also noted that the treatment was well tolerated.

Cytokine release syndrome (CRS) developed in 9 patients: grade 1 in 2 patients, grade 2 in 6 patients, and grade 3 in 1 patient. One patient developed grade 4 tumor lysis syndrome. Treatment of CRS with the IL-6 receptor antagonist tocilizumab was not required.

There was modest residual splenomegaly in 3 of 5 patients, and adenopathy resolved in 4 of 6 patients, with progression in 1 patient.

Ibrutinib reduced CRS apparently by blocking cytokine production by T cells, said Dr Gill, adding, “The combination led to improved efficacy without increased toxicity.”

Ibrutinib may make CAR T-cell therapy more feasible.

Patients who receive ibrutinib for 6 months have a better T-cell response.

“This opens up future discussions of bringing CAR T-cell therapy earlier into CLL treatment,” said Dr Gill.

He envisions patients receiving ibrutinib for 6 months, which would allow time to manufacture T cells, and then have a T-cell infusion.

“Once patients achieve MRD, then we can discuss the possibility of stopping ibrutinib therapy,” he said.

“Most patients remain on ibrutinib, but longer follow-up may show whether remissions are sustained off ibrutinib.”

The researchers have ongoing plans to treat 25 patients with CTL19 plus ibrutinib in a continuation of this trial.

Dr Gill said longer follow-up will reveal the durability of these results “and could support evaluation of a first-line combination approach in an attempt to obviate the need for chronic therapy.” 

Photo © ASCO/David Eulitt 2017

CHICAGO—Chimeric antigen receptor (CAR) T cells combined with ibrutinib enhance T-cell function and can induce complete remission (CR) in patients with chronic lymphocytic leukemia (CLL), researchers report.

Many CLL patients receive ibrutinib treatment, which is well tolerated, but few patients achieve CR.

Immunotherapy with anti-CD19 CAR T cells has induced CR in 25% - 45% of patients with CLL, Saar Gill, MD, of the University of Pennsylvania in Philadelphia, told Hematology Times, and these CRs tend to be durable.

So investigators conducted a pilot trial in 10 patients to test whether combining anti-CD19 CAR T cells with ibrutinib would enhance the CR rate.

Dr Gill reported the findings of the pilot trial at the ASCO 2017 Annual Meeting (abstract 7509).

The patients must have failed at least 1 regimen before ibrutinib, unless they had del(17)(p13.1) or a TP53 mutation.

T cells were lentivirally transduced to express a CAR that included humanized anti-CD19.

Patients were lymphodepleted 1 week before infusion, and ibrutinib was continued throughout the trial.

After a median follow-up of 6 months, 8 of the 9 evaluable patients show absence of CLL in the bone marrow by flow cytometry or minimal residual disease (MRD) negative, and all remain in marrow CR at last follow-up, Dr Gill said.

Radiologic responses are less clear-cut and may require longer follow-up.

“All but 1 patient achieved MRD with deep sequencing. We have deep response in the bone marrow,” Dr Gill said. He also noted that the treatment was well tolerated.

Cytokine release syndrome (CRS) developed in 9 patients: grade 1 in 2 patients, grade 2 in 6 patients, and grade 3 in 1 patient. One patient developed grade 4 tumor lysis syndrome. Treatment of CRS with the IL-6 receptor antagonist tocilizumab was not required.

There was modest residual splenomegaly in 3 of 5 patients, and adenopathy resolved in 4 of 6 patients, with progression in 1 patient.

Ibrutinib reduced CRS apparently by blocking cytokine production by T cells, said Dr Gill, adding, “The combination led to improved efficacy without increased toxicity.”

Ibrutinib may make CAR T-cell therapy more feasible.

Patients who receive ibrutinib for 6 months have a better T-cell response.

“This opens up future discussions of bringing CAR T-cell therapy earlier into CLL treatment,” said Dr Gill.

He envisions patients receiving ibrutinib for 6 months, which would allow time to manufacture T cells, and then have a T-cell infusion.

“Once patients achieve MRD, then we can discuss the possibility of stopping ibrutinib therapy,” he said.

“Most patients remain on ibrutinib, but longer follow-up may show whether remissions are sustained off ibrutinib.”

The researchers have ongoing plans to treat 25 patients with CTL19 plus ibrutinib in a continuation of this trial.

Dr Gill said longer follow-up will reveal the durability of these results “and could support evaluation of a first-line combination approach in an attempt to obviate the need for chronic therapy.”