Transcript Related Guidelines

Novel Therapies in the Treatment of Multiple Myeloma

Nina Shah, MD · University of California at San Francisco

Disclosures

May 12, 2021

Key Takeaways:

  • Novel therapies in the treatment of multiple myeloma include idecabtagene vicleucel (chimeric antigen receptor T cell therapy), melflufen (a novel alkylator), and belantamab mafodotin (BCMA-directed antibody drug conjugate).

  • These novel therapies have completely different mechanisms of action, so it will be necessary to determine how to position and sequence them to get the best and longest patient response.

This transcript has been edited for clarity.

There are a lot of novel therapies that are emerging for the treatment of multiple myeloma.[1] Most recently, we have had approval for the chimeric antigen receptor T cells, also known as CAR-T cells.[2] This is called ide-cel (idecabtagene vicleucel; Abecma) and is a T cell directed and engineered against BCMA. We know that from the data from the pivotal KarMMA study that over 70% of patients responded, and actually over 80% of patients responded at the targeted 450 million dose.[3] The median progression-free survival for these patients at that dose was around a year. So that's something that we're excited about because it's going to be a new therapy that has a completely different mechanism of action.

Now, it will require apheresis, which is the collection of the cells, as well as a wait time of a couple of weeks while those cells are engineered. That's something we're going to have to think about in positioning where this treatment is going to go. The FDA-approved label is for after four lines of treatment.[2] Many of our patients do easily get to five lines of treatment, but I think this is going to be something that we think about as far as, what do we use before that? We don't know exactly the right sequences.

Other novel therapies that have come into play have been the novel alkylator melflufen,[4] which uses sort of a different targeted way, using conjugated melphalan, which uses the aminopeptidases that are actually within the myeloma cell to cleave and give us a higher concentration of melphalan within the myeloma cell. That was recently approved for relapsed/refractory multiple myeloma, with multiple lines of prior therapy.[5,6,7]

Then, of course, we have belantamab mafodotin, last year approved for patients with four treatments prior.[8,9] That is a BCMA-directed antibody drug conjugate. So, we do have a variety of things that have been approved, each of them with a different mechanism of action. The question will be how we're going to position these and sequence this to get the best and longest responses for our patients.

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