Obinutuzumab was FDA approved in November 2017 as first line therapy for follicular lymphoma. The monoclonal antibody was first given in combination with chemotherapy then continued as monotherapy. Obinutuzumab out-performed Rituxan in the GALLIUM trial with a 91% response rate. Obinutuzumab is a monoclonal antibody that targets CD20. Once it binds to this antigen it activates intracellular death. Obinutuzumab induces great antibody-dependent cellular cytotoxicity compared to rituximab as well as direct cell death.
For previously untreated patients obinutuzumab can be administered with bendamustine, CHOP or CVP. After 6-8 cycles of chemotherapy obinutuzumab is continued as monotherapy for 2 years. The monoclonal antibody is administered intravenously.
All patients are pre-medicated to avoid an infusion related reaction.
For bulky disease or renal impairment prophylaxis for tumor lysis syndrome is mandatory.
The most common side effects are infusion reaction, neutropenia, URI, constipation, and diarrhea.
Fatal adverse events occurred in 3% of the patients and the ones on bendamustine had the higher incidence of events.
During the monotherapy period the side effects were considerably less and included hepatitis B reactivation, infusion reaction, hepatic failure, neutropenia, tumor lysis, infection.
Another new treatment for relapsed indolent lymphoma shown to be very effective in recent studies is copanlisib (a phosphatidylinositol 3-kinase inhibitor). It was therefore placed in the accelerated FDA approval. P13K signaling is key for proliferation and survival of malignant b cells. Copanlisib is a P13K inhibitor therefore promotes cell death.
The patients in the trial had received at least two previous lines of therapy.
The response rate was 59% with a complete response rate of 12% stable disease in 30% of patients. The most common side effects were hyperglycemia, diarrhea, fatigue, HTN, and neutropenia. Copanlisib has significant efficacy and safety.