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BCMA-targeted platforms could alter MM therapy


 

Bone marrow aspirate showing MM

New York—Three novel treatment strategies that target B-cell maturation antigen (BCMA) are showing promise in recent multiple myeloma (MM) clinical trials, according to Shaji K. Kumar, MD, of Mayo Clinic Cancer Center in Rochester, Minnesota.

The strategies include B-cell maturation antigen (BCMA) antibody-drug conjugate, BCMA-specific chimeric antigen receptor (CAR) T-cell therapies, and bispecific T-cell engagers (BiTEs).

“Clearly, there are a lot of exciting drugs that are currently in clinical trials, but these 3 platforms appear to be much more advanced than the others, and hopefully we will see that in the clinic in the near future,” Dr. Kumar told attendees at the NCCN 13th Annual Congress: Hematologic Malignancies.

BCMA is required for plasma cell survival and is broadly expressed on malignant plasma cells.

BCMA antibody-drug conjugate

The antibody-drug conjugate, GSK2857916, is a humanized IgG1 anti-BCMA antibody conjugated to a microtubule-disrupting agent. It produced an overall response rate of 67% at the 2 highest dose levels in 9 MM patients who had previously received multiple standard-of-care agents.

“Some of the responses were quite durable, lasting several months,” he said.

Now, GSK2857916 is being evaluated in a variety of different combinations, he said, including in an upcoming phase 2 study of the antibody-drug conjugate in combination with lenalidomide plus dexamethasone or bortezomib plus dexamethasone in patients with relapsed or refractory disease.

BCMA-specific CAR T-cell therapy

Some of the most “exciting” data with anti-BCMA CAR T-cell therapy in myeloma, according to Dr. Kumar, involves bb2121. bb2121 showed durable clinical responses in heavily pretreated patients, according to an ASH 2017 presentation.

“The overall response rate is quite significant,” Dr. Kumar said. He related a 94% rate of overall response that was even higher in patients treated with doses of 150 x 106 CAR+ T cells or more. Many of the responses were lasting, he said, with 5 patients in ongoing response for more than a year.

“The results are exciting enough that this is actually moving forward with registration trials,” Dr. Kumar added.

Another novel CAR T-cell product, LCAR-B38M, has demonstrated promising results. LCAR-B38M principally targets BCMA and has led to a significant number of patients achieving stringent complete response that lasted beyond 1 year.

Multiple BCMA-targeting CAR T-cell products that use different vectors and different costimulatory molecules are currently in clinical trials, Dr. Kumar said.

BiTEs

In contrast to CAR T-cell products that must be customized to each patient in a process that takes weeks, BiTEs are a ready-made approach to allow T cells to engage with tumor cells.

“In patients with advanced disease, a lot can change in that short timeframe, so having an approach that is off-the-shelf, which is not patient specific, is quite attractive,” Dr. Kumar said.

BCMA-directed BiTE therapies to watch that are under investigation include AMG 420 and PF-06863135, he said.

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