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Expert Point of View: Joseph C. Alvarnas, MD, and Henry Fung, MD


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Joseph C. Alvarnas, MD

Joseph C. Alvarnas, MD

Commenting on the ibrutinib (Imbruvica)/chimeric antigen receptor (CAR) T-cell approach at a press conference, Joseph C. Alvarnas, MD, said: “Patients with CLL do not do as well on CAR T-cell therapy as those with B-cell acute lymphoblastic leukemia, and by combining ibrutinib with CAR T cells, the hope is to offset that differential. In patients treated with ibrutinib plus CAR T cells, next-generation sequencing showed a better quality of remission on the molecular level than what you can determine without it. We don’t understand the mechanism for this finding, but it points to a path forward that might not have been evident without this combination.” Dr. Alvarnas is Vice President of Government Affairs at City of Hope, Duarte, California, and moderator at the press conference where this strategy was discussed.

Henry Fung, MD

Henry Fung, MD

“These results are interesting and hypothesis-generating. We need to see more patients treated with this approach and have longer follow-up. Without a control arm, we don’t know if they are true findings,” said Henry Fung, MD, Vice-Chair of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia. “For example, the reduced rate of cytokine-release syndrome seen in both studies using ibrutinib plus CAR T-cell therapy may be a chance finding. If you dig into the details, you can see in the study from Fred Hutch that patients on ibrutinib had 29% bone marrow involvement at baseline compared with 59% for those not on ibrutinib. More disease equals more toxicity. It’s not statistically significant because of the small numbers of patients, but those who continue on ibrutinib tend to have less disease bulk, which predicts for less cytokine-release syndrome.”

Dr. Fung added, “Potentially, using ibrutinib plus CAR T cells could improve efficacy and reduce toxicity in CLL and other malignancies such as diffuse large B-cell lymphoma and mantle cell lymphoma. We need greater patient numbers and more data.” 

DISCLOSURE: Drs. Alvarnas and Fung reported no conflicts of interest.


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