Expert Point of View: Nitin Jain, MD, and Susan O'Brien, MD


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Nitin Jain, MD

Nitin Jain, MD

Formal discussant of the GENUINE trial, Nitin Jain, MD, of The University of Texas MD Anderson Cancer Center, Houston, noted that the majority of responses to ibrutinib (Imbruvica) in high-risk patients are partial responses. “These patients [have disease progression] even in the context of ibrutinib therapy, but responses are better than with chemotherapy,” Dr. Jain said. 

“The GENUINE study clearly shows higher overall response rates and higher [minimal residual disease] negativity when ublituximab is added to ibrutinib. Longer follow-up is needed to see if there is a progression-free survival difference. From a clinical standpoint, the earlier resolution of lymphocytosis is noted,” Dr. Jain continued. 

“The type of anti-CD20 monoclonal antibody may matter. Several ongoing studies should define the role of rituximab (Rituxan) vs obinutuzumab (Gazyva) vs ublituximab,” he stated. 

Another View 

Susan O'Brien, MD

Susan O'Brien, MD

Susan O'Brien, MD, of the University of California, Irvine, said that ibrutinib achieves a rapid response in the lymph nodes but also causes lymphocytosis. About 4 to 8 months later, this tends to resolve. “But if you give ibrutinib with an anti-CD20 antibody, patients get to partial response much faster, and you abrogate the lymphocytosis. The question is whether the response rate with the combination is better than with ibrutinib alone if you waited longer to determine response,” she said. 

“Five-year experience with ibrutinib shows that the best overall response rate is 90%. The package insert says the overall response rate ranges from 50% to 60%, but response rates with ibrutinib go up over time,” Dr. O’Brien noted in an interview. 

“The most important questions regarding this combination are whether the complete response rates will be higher and whether the remissions are more durable. We will find out with longer follow-up,” she said. ■

DISCLOSURE: Dr. Jain has served as a consultant/advisory role with Pharmacyclics, Novartis, ADC Therapeutics, Pfizer, Servier, Novimmune, and Adaptive Biotechnologies. He has received institutional research funding from Pharmacyclics, Genentech, Abbvie, Pfizer, Incyte, BMS, Infinity, ADC Therapeutics, Seattle Genetics, Celgene, and Servier. Dr. O’Brien reported no conflicts of interest. 


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