Translating Novel CLL Therapies to Other Types of NHL

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Many of the novel agents that have demonstrated promise as treatments for patients with chronic lymphocytic leukemia (CLL) are now being researched as potential therapies for patients with indolent non-Hodgkin's lymphoma (iNHL), including ibrutinib and venetoclax (ABT-199). However, there is a steep dichotomy between the treatments that are available for patients with follicular lymphoma (FL) and those for patients with CLL, notes John C. Byrd, MD. In many cases, similar findings can be demonstrated with one agent across both diseases; however, toxicity rates will vary between the two groups.

In July, the FDA simultaneously approved idelalisib for both CLL and FL, based on separate clinical trials. In the phase II study that led to the FL approval, the overall response rate (ORR) with single-agent idelalisib was 54% in patients with relapsed FL (n = 72). In a phase I study of single-agent idelalisib in patients with relapsed/refractory CLL (n = 54), the ORR was 56%. In these studies, the doses varied, as did the side effects.

Another example of the differences between the two types of NHL can be seen with lenalidomide, explains Thomas J. Kipps, MD. In patients with FL, lenalidomide can be started at 15 mg or higher without side effect concerns; however, patients with CLL have difficulty tolerating higher doses.

In terms of optimizing the treatment of patients with FL, data from a phase III study investigating bendamustine plus rituximab (B-R) versus fludarabine plus rituximab (F-R) in relapsed FL, other indolent lymphoma, and mantle cell lymphoma demonstrated significant advantage with the B-R regimen, notes Byrd. In this trial, the median progression-free survival with B-R was 34 versus 12 months with F-R (HR = 0.54; P < .0001). The ORR was 83.5% with B-R compared with 52.5% with F-R (P < .0001). The complete response rate with B-R was 38.5% versus 16.2% with F-R (P = .0004).