Dr. Younes: So there are a few new agents that are promising for the treatment of indolent non-Hodgkin lymphoma—and mainly we are talking about indolent B-cell non-Hodgkin lymphoma.1,2 I think the leading compounds are the BTK [Bruton tyrosine kinase] inhibitor ibrutinib and the PI3 [phosphatidylinositol 3] kinase inhibitor idelalisib, which is a PI3 kinase delta-specific inhibitor.
Narrator: Idelalisib has been studied as a single agent in patients with recurrent indolent lymphoma, and its use resulted in significant tumor shrinkage in the majority of patients.3,4 Ibrutinib has shown single-agent activity in follicular lymphoma, including in patients with resistant disease.5 Several trials are evaluating these compounds as monotherapy or in combination with other targeted therapies in patients with indolent NHL.6,7
Dr. Younes: Both are oral drugs that have shown a very good safety profile [in] that they can be administered for a long time with manageable side effects and toxicities; and also they both produce reasonably high response rates that are durable. Both are currently not approved by the FDA, but it is hoped that both of them would be approved at one point for the treatment of patients with indolent B-cell lymphoma.
Other agents fall into two major classes of drugs. One is the antibody-drug conjugates [ADC], and there are a few of them in clinical trials with early signs of potential activity; although, it is too early to call at the present time which one would be a winner. Those ADCs target CD19, CD22, CD79, and there are more on the horizon.
And the other class of agents, which is called the checkpoint blockade inhibitors, mainly the PD-1/PD-L1 monoclonal antibodies. The phase 1 and 2 studies are currently ongoing for B-cell lymphomas, but there are also early encouraging signs that this strategy may be fruitful in the future.
The immunomodulatory agents [IMA] have some activity in follicular lymphoma, and they are currently being incorporated in clinical trials,8,9 although the leading compound, lenalidomide, has not been approved. So for indolent lymphoma, lenalidomide has been combined with rituximab as a doublet to treat patients with newly diagnosed, advanced-stage follicular lymphoma requiring therapy. So this would be the first non-chemotherapy combination regimen—combining lenalidomide with rituximab—that would be compared with standard chemotherapy.
Narrator: As some examples of studies looking at the combination of lenalidomide plus rituximab, a trial from The University of Texas MD Anderson Cancer Center evaluated the combination as an initial treatment for indolent lymphoma.10 The overall response rate was 97%, with the majority of patients achieving complete responses. Further follow-up data from this study are awaited. Another more recent study of lenalidomide plus rituximab included patients with stage III to IV or bulky stage II, grade 1 to 3a, FLIPI 0 to 2 score disease.11 In this trial, the combination showed an overall response rate of 93% and a complete response rate of 70%. There is considerable interest in moving forward with this and other biologic doublets that do not include chemotherapy.