Combination Therapy in Large Cell Lymphomas

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The combination of lenalidomide (Revlimid) plus rituximab (R-square) is highly effective in follicular and mantle cell lymphoma, notes Brad S. Kahl, MD. The phase III RELEVANCE study has been initiated to compare the frontline efficacy and safety of rituximab plus lenalidomide with rituximab plus chemotherapy (CHOP, CVP) or rituximab and bendamustine for patients with CD20-positive grade 1, 2 or 3a follicular lymphoma.

A phase II study conducted by the Mayo Clinic showed that the addition of lenalidomide to R-CHOP reduced the negative prognostic significance of the non-germinal center B-cell (non-GCB) phenotype for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), points out Kahl. In addition to this combination, ibrutinib has also shown promise in the activated B cell (ABC) subtype of DLBCL, adds John C. Byrd, MD. Together, these agents offer promise for a hard to treat group of patients.

Fitting the multiple new drugs into the treatment paradigm will represent the next hurdle to overcome, particularly in chronic lymphocytic leukemia, believes Byrd. Finding the right treatment sequence is exceptionally important, since the optimal use of already available drugs can dramatically improve outcomes, as was the case in acute lymphocytic leukemia, points out Dan Douer, MD.

As more of these agents gain approval, the clinical trial endpoint of prolongation in overall survival will be more difficult to achieve, enhancing the need for surrogate endpoints, Michael C. Lill, MD, states. At this point, it seems likely that minimal residual disease will emerge as the surrogate endpoint of choice, Byrd believes.