How safe and effective is the combination of ibrutinib, lenalidomide, and rituximab for relapsed or refractory mantle cell lymphoma?

This study investigated the safety and effectiveness of ibrutinib (Imbruvica), lenalidomide (Revlimid), and rituximab (Rituxan) given together to patients with relapsed or refractory (not responding to treatment) mantle cell lymphoma (MCL). The authors conclude that this combination is effective in these patients, but not better than the combination of lenalidomide and rituximab or ibrutinib alone.

Mantle cell lymphoma (MCL) is an aggressive type of non-Hodgkin’s lymphoma (NHL). This type represents about 6% of all new NHL cases in the U.S and is more common in older adults. The standard treatment for MCL is rituximab combined with other drugs, although chemotherapy is also used.  For patients with relapsed or refractory disease, additional therapy options include novel drugs like ibrutinib and lenalidomide.

Ibrutinib is a targeted therapy. This type of treatment targets a specific protein on cancer cells, and prevents them from growing. This leads to cancer cell death. Lenalidomide blocks growth of blood vessels needed by the tumor and helps the immune system attack them, leading to cancer cell death. Rituximab is a monoclonal antibody. This type of treatment binds to cancer cells, leading to cancer cell death.

The combination of rituximab and lenalidomide has achieved better results in patients with relapsed or refractory MCL than lenalidomide alone. However, it is unclear whether adding ibrutinib to this combination makes it more effective.

This study involved 50 patients with relapsed or refractory MCL. 84% of patients had stage 4 disease and 16% of patients had refractory disease. The average follow-up period was 17.8 months.

The overall response (cancer shrinks or disappears after treatment) rate was 76%. Of this, 56% of patients showed complete remission (tumor disappearance) and 20% showed partial remission (tumor shrinkage). Only 1 patient had stable disease (tumors are not growing nor shrinking). The progression-free survival (time from treatment before disease progression) rate at 1 year was 56.9%. The overall survival (time from treatment until death from any cause) rate at 1 year was 77.6%. The average overall survival was 22 months.

At follow-up, 68% of patients had discontinued treatment. This was due to disease progression in 34%, and due to side effects in 10%. The most common blood-related side effects include low platelet count (28%), low red blood cell count (18%), and low white blood cell count (38%). Of these, 52% were severe or life-threatening, including all reported cases of low white blood cell count. 14% of patients had dose reductions due to side effects. Patients also reported gastrointestinal side effects (80%), infections (62%), and skin rash (70%). Of these, 52% were severe or life-threatening.

40% of patients died during the study. Of these, 85% were due to disease progression.

The authors concluded that in patients with relapsed or refractory MCL, the combination of ibrutinib, lenalidomide, and rituximab is effective but not better than the combination of ibrutinib and rituximab or ibrutinib alone.

The sample size in this study is small, so the results need to be confirmed in larger clinical trials.

This study did receive some funding from Celgene, the manufacturer of lenalidomide. The company reviewed the study manuscript before submission, but it was not involved in the study’s design or data collection.