A number of therapeutic approaches are being evaluated for the treatment of multiple myeloma with very promising assets in the pipeline. Credit: Shutterstock + David A Litman.

A number of therapeutic approaches are being evaluated for the treatment of multiple myeloma with very promising assets in the pipeline.

B-cell maturation antigen (BCMA) directed chimeric antigen receptor T (CAR-T) cell therapy for heavily pre-treated patients and several other combination regimens have shown significant excitement among physicians treating multiple myeloma patients. About 20 drugs were approved in the last 15 years for this space, thus leading to a constant change in the treatment paradigm. One treatment modality of very high interest is BCMA-targeted drugs, with a higher excitement among key opinion leaders (KOLs) owing to these creating a significant impact upon approval. A few pipeline BCMA assets in development with promising results are bb2121, JNJ-4528, CC-93269, AMG 701, and belantamab mafodotin.

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Bluebird’s bb2121 is the most awaited drug for 2020 in multiple myeloma, with an expected launch in the US for heavily pre-treated multiple myeloma patients. It will be the first CAR-T therapy to be approved for multiple myeloma, and so is expected to gain the first-to-market advantage. Other combinations such as J&J/Janssen’s Darzalex (daratumumab) with Amgen’s Kyprolis (carfilzomib) in the relapsed/refractory setting, and bispecific T cell engager in heavily pretreated / refractory patients, have shown some promising results along with a moderate level of KOL excitement.

The GRIFFIN and CANDOR studies that looked at Darzalex with standard triplet RVd combination versus RVd therapy alone in frontline pre-transplanted induction patients newly diagnosed with multiple myeloma, and Darzalex in combination with Kyprolis with dexamethasone for relapsed/refractory multiple myeloma patients, respectively, have some encouraging early-stage results. However, the data showing some early promising results in progression-free survival (PFS) and overall survival (OS), which will be the determining endpoints for approval, are still under evaluation. The Darzalex-Kyprolis-Revlimid-Dex (NCT01998971) quadruplet combination is showing some promising results for being an effective frontline therapy and upon approval in 2024, it is expected to have a significant positive impact on the treatment paradigm.

One of the key challenges in the multiple myeloma space is that patients develop drug resistance very easily, triggering the need for different therapeutic modalities to be evaluated, even after the launch of current pipeline drugs. Even in the case of the current CAR-T cell therapy bb2121, it has still not proved to be a cure and the therapy will face challenges with the supply chain process, as the overall turnaround time for processing the cells can take about a month, which is a relatively long period of time for these patients who generally progress at a faster rate.

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