Expert Point of View: Kenneth C. Anderson, MD, FASCO, Adam D. Cohen, MD, Craig Hofmeister, MD, MPH, and Bruce Cheson, MD


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Kenneth C. Anderson, MD, FASCO

Kenneth C. Anderson, MD, FASCO

Adam D. Cohen, MD

Adam D. Cohen, MD

Craig Hofmeister, MD, MPH

Craig Hofmeister, MD, MPH

Bruce Cheson, MD

Bruce Cheson, MD

Kenneth C. Anderson, MD, FASCO, of Dana-Farber Cancer Institute, Boston, noted that the iNNOVATE trial is the first randomized comparison of ibrutinib (Imbruvica) plus rituximab (Rituxan) vs “a very active control—rituximab—to which 50% of patients responded.” The study showed that “the addition of a very active novel agent can add to the monoclonal antibody standard of care,” Dr. Anderson said. “The increased efficacy and safety, shown in a randomized trial, demonstrate the utility and superiority of that doublet.” 

Adam D. Cohen, MD, of Abramson Cancer Center, Philadelphia, who said he primarily uses ibrutinib as a single agent, predicted the results could change practice. The study was designed, however, when single-agent rituximab was the standard treatment, and he thought single-agent ibrutinib would be a better control arm. “The question of ibrutinib/rituximab vs single-agent ibrutinib is the question we want to answer,” Dr. Cohen said. 

Craig Hofmeister, MD, MPH, of Winship Cancer Institute of Emory University, Atlanta, expressed caution about tolerability, noting that this study showed clinically significant atrial fibrillation (12% vs 1% with rituximab alone), pneumonia (12% vs 3% with rituximab alone), and minor bleeding (51% vs 21% with rituximab alone) with this combination. 

“The use of ibrutinib plus rituximab in Waldenström’s macroglobulinemia in MYD88-mutated disease is appealing,” Dr. Hofmeister said, “but atrial fibrillation and infections require close monitoring.”

Anecdotal Safety of Acalabrutinib

Bruce Cheson, MD, Deputy Chief, Division of Hematology/Oncology at Lombardi Comprehensive Cancer Center, Washington, DC, believes that acalabrutinib (Calquence) will be a more tolerable Bruton tyrosine kinase inhibitor in this disease. “When we look at the various diseases in which both drugs have been evaluated, the response data are similar, as best as we can determine by looking across studies, but acalabrutinib appears to be a safer drug,” he told The ASCO Post.

“I’ve used a fair amount of acalabrutinib, and what we mostly see is headache, which responds to caffeine,” he said. “We have not seen atrial fibrillation, extensive bleeding, diarrhea, or arthralgias to the extent that we see with ibrutinib.”

Dr. Cheson added that he has enrolled patients on a trial in which they are switched over to acalabrutinib if they are intolerant of ibrutinib, “and once they leave ibrutinib and go to acalabrutinib, they say it’s a whole new ballgame—they feel much better.” The findings from this study have not yet been reported. ■

DISCLOSURE: Dr. Anderson is an advisor for Millennium, Bristol-Myers Squibb, and Gilead. Drs. Cohen and Hofmeister reported no conflicts of interest. Dr. Cheson is a consultant and/or advisor for AbbVie, Acerta Pharma, Bayer, MorphoSys, Celgene, Pharmacyclics/Janssen, Roche/Genentech, Sunesis Pharmaceuticals, and TG Therapeutics.


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