Dr. Raje Discusses Investigational Treatment Strategies in Multiple Myeloma

Noopur Raje, MD, director, Center for Multiple Myeloma, Massachusetts General Hospital, discusses updates on investigational treatment strategies in multiple myeloma presented at the 2018 ASH Annual Meeting.

There is a growing body of knowledge on chimeric antigen receptor (CAR) T-cell therapy, a modality that differs from most systemic therapies in multiple myeloma. At the meeting, data were presented on several CAR T-cell products, including phase I/II data on the use of the BCMA-targeted CAR T-cell therapy LCAR-B38M, from Legend Biotech, in patients with advanced relapsed/refractory myeloma. The therapy is a bispecific CAR that targets 2 different epitopes of the BCMA molecule. Data from the LEGEND-2 trial evaluating LCAR-B38M showed an overall response rate (ORR) of 88% and a 74% complete response (CR) rate in this patient population. Although patients were not as heavily pretreated as those who received bb2121, the data show that this is an active product.

Data on JCARH125, another CAR T-cell product that targets BCMA, were also presented. Preliminary results revealed high CRs, although slightly higher rates of toxicity. More follow-up data will be needed to see how it compares with other products, says Raje. Finally, bb21217, the next-generation product of bb2121, showed an ORR of 83% with comparable toxicity to bb2121. As more follow-up data are reported on bb2121, physicians may be able to bring it into earlier lines of therapy, adds Raje.

In addition to BCL-2, MCL1 has been put forward as a potential target in myeloma. About 20% to 30% of myelomas express BCL2—the rest are MCL1 dependent. An MCL1 inhibitor from AstraZeneca, referred to as AZD5991, is currently being evaluated in combination with venetoclax (Venclexta) and has shown dramatic preclinical responses in patients with relapsed/refractory hematologic malignancies.

The practice-changing MAIA study built upon the initial study evaluating the use of lenalidomide (Revlimid) and dexamethasone (Rd) for transplant-ineligible patients, explains Raje. In the trial, over 700 patients were randomized to receive either Rd or Rd plus daratumumab (Darzalex). At a median follow-up of 28 months, the progression-free survival was 31 months with Rd and had yet to be reached with the addition of daratumumab. Daratumumab is already approved by the FDA for frontline use in combination with bortezomib (Velcade), melphalan, and prednisone (VMP) based on data from the ALCYONE trial.