Lenalidomide plus rituximab achieves 87% response rate

First-line combination biologic therapy with lenalidomide plus rituximab produced an 87% overall response rate in stage 3-4 mantle cell lymphoma, in an industry-sponsored, phase II clinical trial reported online Nov. 5 in the New England Journal of Medicine.

Mantle cell lymphoma is generally incurable, and patients have a median survival of 4-5 years. Initial therapy is usually very intensive, involving high-dose chemotherapy and hematopoietic cell transplantation. Since the malignancy primarily affects older adults who aren’t suitable candidates for intensive regimens, treatment “remains a clinical challenge,” said Dr. Jia Ruan of the Meyer Cancer Center and the division of biostatistics and epidemiology, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, and her associates.

Courtesy Wikimedia Commons/Nephron/Creative Commons

Reasoning that biologic therapy might offer effective disease control with fewer and less intense adverse effects, the investigators performed the open-label, single-group trial over a 3-year period. They treated 38 patients whose mean age was 65 years (range, 42-86 years), most of whom were at intermediate or high risk for imminent progression. These participants received a 12-cycle induction phase of lenalidomide plus rituximab, followed by a maintenance phase until disease progressed, unacceptable adverse effects developed, or patients withdrew from the study. The median follow-up was 30 months (range, 10-42 months).

The primary endpoint – overall response rate – was 87% in the intention-to-treat population, and the complete response rate was 61%. The number of complete responses increased over time with continuing treatment: the median time to a partial response was 3 months, and the median time to a complete response was 11 months. Two-year progression-free survival was 85%, and 2-year overall survival was 97%, the investigators said (New Engl. J. Med. 2015 Nov 5. doi: 10.1056/NEJMoa1505237).

Only eight patients showed progression of mantle cell lymphoma while taking lenalidomide plus rituximab, two of whom died from their disease. The other six patients responded to second-line therapy and remain alive, indicating that this first-line combination biologic therapy doesn’t compromise outcomes after subsequent treatments, Dr. Ruan and her associates said.

Almost as important as these favorable survival results were the findings concerning adverse effects. Scores on several quality-of-life measures either remained stable or improved throughout the induction and maintenance phases of treatment. As expected, grade 3 or 4 hematologic adverse effects included neutropenia (50% of patients), thrombocytopenia (13%), and anemia (11%), all of which resolved; grade 3 or 4 nonhematologic adverse effects included rash (29%), tumor flare (11%), serum sickness (8%), and fatigue (8%), all of which also resolved. All the serious infections that developed during the maintenance phase of treatment, which included pneumonia, cholangitis, and West Nile viral encephalitis, also resolved with antibiotics and supportive care.

Secondary cancers that developed during follow-up included two squamous cell skin cancers, one basal cell skin cancer, two cases of melanoma in situ, one Merkel cell carcinoma, and one pancreatic cancer.

“Our data show that a lower-intensity approach for initial therapy than that usually used in the case of patients with this cancer can be highly active, with durable responses observed in most patients,” Dr. Ruan and her associates said.

This study was supported by Celgene, maker of lenalidomide, and a Weill Cornell Medical College Clinical Translational Science Center grant. Dr. Ruan reported ties to Celgene, and her associates reported ties to numerous industry sources.

First-line combination biologic therapy with lenalidomide plus rituximab produced an 87% overall response rate in stage 3-4 mantle cell lymphoma, in an industry-sponsored, phase II clinical trial reported online Nov. 5 in the New England Journal of Medicine.

Mantle cell lymphoma is generally incurable, and patients have a median survival of 4-5 years. Initial therapy is usually very intensive, involving high-dose chemotherapy and hematopoietic cell transplantation. Since the malignancy primarily affects older adults who aren’t suitable candidates for intensive regimens, treatment “remains a clinical challenge,” said Dr. Jia Ruan of the Meyer Cancer Center and the division of biostatistics and epidemiology, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, and her associates.

Courtesy Wikimedia Commons/Nephron/Creative Commons

Reasoning that biologic therapy might offer effective disease control with fewer and less intense adverse effects, the investigators performed the open-label, single-group trial over a 3-year period. They treated 38 patients whose mean age was 65 years (range, 42-86 years), most of whom were at intermediate or high risk for imminent progression. These participants received a 12-cycle induction phase of lenalidomide plus rituximab, followed by a maintenance phase until disease progressed, unacceptable adverse effects developed, or patients withdrew from the study. The median follow-up was 30 months (range, 10-42 months).

The primary endpoint – overall response rate – was 87% in the intention-to-treat population, and the complete response rate was 61%. The number of complete responses increased over time with continuing treatment: the median time to a partial response was 3 months, and the median time to a complete response was 11 months. Two-year progression-free survival was 85%, and 2-year overall survival was 97%, the investigators said (New Engl. J. Med. 2015 Nov 5. doi: 10.1056/NEJMoa1505237).

Only eight patients showed progression of mantle cell lymphoma while taking lenalidomide plus rituximab, two of whom died from their disease. The other six patients responded to second-line therapy and remain alive, indicating that this first-line combination biologic therapy doesn’t compromise outcomes after subsequent treatments, Dr. Ruan and her associates said.

Almost as important as these favorable survival results were the findings concerning adverse effects. Scores on several quality-of-life measures either remained stable or improved throughout the induction and maintenance phases of treatment. As expected, grade 3 or 4 hematologic adverse effects included neutropenia (50% of patients), thrombocytopenia (13%), and anemia (11%), all of which resolved; grade 3 or 4 nonhematologic adverse effects included rash (29%), tumor flare (11%), serum sickness (8%), and fatigue (8%), all of which also resolved. All the serious infections that developed during the maintenance phase of treatment, which included pneumonia, cholangitis, and West Nile viral encephalitis, also resolved with antibiotics and supportive care.

Secondary cancers that developed during follow-up included two squamous cell skin cancers, one basal cell skin cancer, two cases of melanoma in situ, one Merkel cell carcinoma, and one pancreatic cancer.

“Our data show that a lower-intensity approach for initial therapy than that usually used in the case of patients with this cancer can be highly active, with durable responses observed in most patients,” Dr. Ruan and her associates said.

This study was supported by Celgene, maker of lenalidomide, and a Weill Cornell Medical College Clinical Translational Science Center grant. Dr. Ruan reported ties to Celgene, and her associates reported ties to numerous industry sources.

First-line combination biologic therapy with lenalidomide plus rituximab produced an 87% overall response rate in stage 3-4 mantle cell lymphoma, in an industry-sponsored, phase II clinical trial reported online Nov. 5 in the New England Journal of Medicine.

Mantle cell lymphoma is generally incurable, and patients have a median survival of 4-5 years. Initial therapy is usually very intensive, involving high-dose chemotherapy and hematopoietic cell transplantation. Since the malignancy primarily affects older adults who aren’t suitable candidates for intensive regimens, treatment “remains a clinical challenge,” said Dr. Jia Ruan of the Meyer Cancer Center and the division of biostatistics and epidemiology, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, and her associates.

Courtesy Wikimedia Commons/Nephron/Creative Commons

Reasoning that biologic therapy might offer effective disease control with fewer and less intense adverse effects, the investigators performed the open-label, single-group trial over a 3-year period. They treated 38 patients whose mean age was 65 years (range, 42-86 years), most of whom were at intermediate or high risk for imminent progression. These participants received a 12-cycle induction phase of lenalidomide plus rituximab, followed by a maintenance phase until disease progressed, unacceptable adverse effects developed, or patients withdrew from the study. The median follow-up was 30 months (range, 10-42 months).

The primary endpoint – overall response rate – was 87% in the intention-to-treat population, and the complete response rate was 61%. The number of complete responses increased over time with continuing treatment: the median time to a partial response was 3 months, and the median time to a complete response was 11 months. Two-year progression-free survival was 85%, and 2-year overall survival was 97%, the investigators said (New Engl. J. Med. 2015 Nov 5. doi: 10.1056/NEJMoa1505237).

Only eight patients showed progression of mantle cell lymphoma while taking lenalidomide plus rituximab, two of whom died from their disease. The other six patients responded to second-line therapy and remain alive, indicating that this first-line combination biologic therapy doesn’t compromise outcomes after subsequent treatments, Dr. Ruan and her associates said.

Almost as important as these favorable survival results were the findings concerning adverse effects. Scores on several quality-of-life measures either remained stable or improved throughout the induction and maintenance phases of treatment. As expected, grade 3 or 4 hematologic adverse effects included neutropenia (50% of patients), thrombocytopenia (13%), and anemia (11%), all of which resolved; grade 3 or 4 nonhematologic adverse effects included rash (29%), tumor flare (11%), serum sickness (8%), and fatigue (8%), all of which also resolved. All the serious infections that developed during the maintenance phase of treatment, which included pneumonia, cholangitis, and West Nile viral encephalitis, also resolved with antibiotics and supportive care.

Secondary cancers that developed during follow-up included two squamous cell skin cancers, one basal cell skin cancer, two cases of melanoma in situ, one Merkel cell carcinoma, and one pancreatic cancer.

“Our data show that a lower-intensity approach for initial therapy than that usually used in the case of patients with this cancer can be highly active, with durable responses observed in most patients,” Dr. Ruan and her associates said.

This study was supported by Celgene, maker of lenalidomide, and a Weill Cornell Medical College Clinical Translational Science Center grant. Dr. Ruan reported ties to Celgene, and her associates reported ties to numerous industry sources.