Expert Point of View: Parameswaran Hari, MD


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Parameswaran Hari, MD

Parameswaran Hari, MD

FORMAL DISCUSSANT Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee, was impressed by many aspects of the bb2121 study, which represents the “largest and most mature” data set for the chimeric antigen receptor (CAR) T-cell approach in myeloma, he noted. 

According to Dr. Hari, B-cell maturation antigen (BCMA) is “the latest promising target in multiple myeloma,” for which there are at least three interesting approaches: (1) CAR T cells directed against BCMA; (2) bispecific T-cell engager (BiTE) antibodies, ie, BCMA/CD3-bispecific engagers; (3) and antibody-drug conjugates (ADCs) against BCMA. For the CAR T-cell approach, at least 18 clinical trials are ongoing worldwide, he said. 

‘Not Yet a Cure’ 

THE STUDY OF bb2121 shows this construct to be active and to induce rapid and deep responses, producing more complete and very good partial responses than partial responses along with early establishment of minimal residual disease (MRD) negativity. Progression-free survival in MRD-negative patients was 17.7 months, he noted. 

Soluble BCMA (not on the myeloma cells) is not an issue, “as was feared,” and the safety profile was comparable to or better than that of most other CAR T-cell approaches in myeloma and lymphoma, according to Dr. Hari. 

Responses correlated with CAR T-cell expansion, and cell dose mattered, but BCMA expression did not appear to be important for response, at least in the early data, he continued. 

“Unfortunately, patients still relapsed,” he pointed out. “The median duration of response was about 11 months and longer in those achieving MRD negativity.” This begs further questions: “What does MRD negativity mean in this setting of multiple relapses?” Do we need post– CAR T-cell therapy to prevent relapses? Are any of the off-the-shelf approaches such as BiTEs or ADCs more timely and useful?” Unfortunately, he concluded, “CAR T-cell therapy in myeloma is not yet a cure.” ■

DISCLOSURE: Dr. Hari has been a consultant and/or advisor for Celgene, Kite, Juno, Spectrum, Takeda, and Amgen.


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IN AN UPDATE of a phase I trial, a heavily pretreated population of patients with multiple myeloma continued to respond to the chimeric antigen receptor (CAR) T-cell therapy bb2121.1 The results presented at the 2018 ASCO Annual Meeting confirmed previous findings for bb2121 in the dose-escalation...

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