These results of RESONATE-2 are not a surprise to anyone. The relevance—in my opinion—is not the efficacy but rather that these results can serve as a registration strategy for upfront therapy.
—Susan M. O’Brien, MD
Until recently, chlorambucil (Leukeran) was the standard of care for older patients with chronic lymphocytic leukemia (CLL) in Europe. In several studies, chlorambucil combined with newer drugs—for example, anti-CD20 antibodies, obinutuzumab (Gazyva), or ofatumumab (Arzerra)—improved survival, explained Susan M. O’Brien, MD, Associate Director for Clinical Science for the Chao Family Comprehensive Cancer Center and Medical Director of the Sue and Ralph Stern Center for Cancer Clinical Trials and Research at the University of California, Irvine.
“FCR [fludarabine, cyclophosphamide, and rituximab (Rituxan)]-like regimens are too myelosuppressive for older patients with comorbidities. These results of RESONATE-2 are not a surprise to anyone. The relevance—in my opinion—is not the efficacy but rather that these results can serve as a registration strategy for upfront therapy. I would think that ibrutinib [Imbruvica] will get an indication at least for upfront therapy in people aged 65 and older, which represents about 50% of all CLL patients who need treatment,” Dr. O’Brien commented.
“Obviously this is huge. Any older patient who requires therapy will get ibrutinib. What will be more controversial will be if the drug gets a broader approval for upfront therapy agewise. Chlorambucil is unacceptable for younger fit patients with CLL. Three published trials with different follow-up showed that with FCR there is a plateau for progression-free survival in younger fit patients with mutated IGVH [immunoglobulin variable region heavy chain gene], suggesting that these patients are cured by FCR. So it will be interesting to see where ibrutinib will fit in for younger patients with favorable cytogenetics,” she said. ■
Disclosure: Dr. O’Brien reported no potential conflicts of interest.
First-line treatment with the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) significantly reduced the risk of dying or disease progression compared with chlorambucil (Leukeran) in older treatment-naive patients with chronic lymphocytic leukemia (CLL) in the RESONATE-2 trial. At the time...