Meletios A. Dimopoulos, MD
Results from the phase III iNNOVATE (PCYC-1127) trial established the combination of ibrutinib (Imbruvica) plus rituximab (Rituxan) as the new standard of care in Waldenström macroglobulinemia, said Meletios A. Dimopoulos, MD.
, Dimopoulos discussed what he hopes to see in the final analysis of iNNOVATE and the development of future treatments for Waldenström macroglobulinemia.
OncLive: What was the rationale for this trial?
: Waldenström macroglobulinemia is an unusual, low-grade lymphoplasmacytic lymphoma. Among active treatments for this disease, we have the anti-CD20 monoclonal antibody rituximab, which has been around for 25 years. It is one of the most frequent therapies given as a single agent. Among other agents, we have nucleoside analogues, we have proteasome inhibitors, and in the past few years, there has been a significant interest for treating this disease with BTK inhibitors. The first one was ibrutinib.
The primary endpoint of the study was PFS, with secondary endpoints being OS, ORR, safety, and tolerability.
What were the findings?
At the time of the first interim analysis, we observed a highly significant, statistically very important difference in favor of the investigational arm, with a hazard ratio [per investigator assessment] of 0.22. With a median follow-up of 29 months, the median PFS with rituximab and placebo was 22 months, whereas it has not been reached for the investigational arm.
Furthermore, the ORR for patients treated with ibrutinib and rituximab was 92% if one takes into consideration minor responses, as well. Other clinically relevant observations were the abrogation of the IgM flood effect, which we see when patients get only rituximab, the elimination of the rituximab-associated diffusion reactions, and the very significant improvements of the hemoglobin, which occurred in 95% of the patients who were treated.
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