Future Directions in Multiple Myeloma Treatment

EP: 1.Evolving Treatment Paradigms in Multiple Myeloma

EP: 2.BCMA-Targeted CAR T-Cell Therapies in Multiple Myeloma

EP: 3.The Impact of CAR T-Cell Therapy on MM Treatment Paradigms

EP: 4.Allogeneic CAR T-Cell Therapy and Other Technology Advances in Multiple Myeloma

EP: 5.MM Therapies: Bispecific Antibodies and T-Cell Engagers

EP: 6.Bispecific Antibodies Under Investigation in Multiple Myeloma

EP: 7.Treatment Sequencing in MM

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EP: 8.Future Directions in Multiple Myeloma Treatment

EP: 9.Closing Remarks on the MM Treatment Landscape

Transcript:

David Siegel, MD: We shouldn’t confine these conversations about myeloma to just the technologies we’re using now. There are going to be a lot of other interesting things that are coming along. I’m certainly happy to talk about the things I think are exciting. What do you think are the exciting things on the horizon?

Noa Biran, MD: I think reintroducing the use of checkpoint inhibitors early in the disease state where you have maximal debulking and immune reconstitution can change the natural history of the disease. And I think we need to look more at preclinical data and correlative data on what’s happening to those immune cells pre- and post-treatment. Giving patients maybe an autologous transplant, and then consolidating that with checkpoint inhibitors in combination with IMiDs [immunomodulatory drugs] with careful monitoring of immune-mediated AEs [adverse effects], and hopefully changing the natural history of the disease. We certainly have proof that that concept has made a difference in the lives of patients. I think that’s an interesting area to explore further.

David Siegel, MD: Noa is being inappropriately modest. Some of the audience will be people knowledgeable about the biology we’re talking about, others will not. As far as checkpoint inhibitors, the main purpose of our immune system evolutionarily is to protect us from infections. As we evolved, we didn’t live to be in our 60s, 70s, 80s, and 90s, and get cancer as a major threat. The major threat was an infection. And so our immune system has developed all kinds of checkpoints to make sure that our response to infections doesn’t get out of control. One of the major discoveries in oncology over the last generation was that you could interfere with some of those checkpoints. You could suppress them with checkpoint inhibitors. And you could start curing people with all kinds of diseases, which had been a fantasy even relatively recently. The start of all this was in melanoma. For people my age, there was no cancer that sounded scarier than melanoma. If you got it, you were going to die, and you were going to die quickly. And now, people can live for decades, and some of them are probably cured because you can harness the immune system to kill the melanoma by inhibiting these checkpoints, checkpoint inhibition.

In myeloma, we’re way behind. There have been some clinical trials done, and I was fortunate enough to participate in some of them, that suggested that they were effective. Dr Biran was the principal investigator on a unique trial in which patients got stem cell transplants—and stem cell transplants are still the most universally applicable and potentially curative therapy we have. But [the goal was] to take patients who had terrible versions of myeloma and give them checkpoint inhibitors after a stem cell transplant, and some of these patients have had miraculous outcomes.

Unfortunately, there was a series of clinical trials done that I think were poorly executed, and the FDA decided that checkpoint inhibition in myeloma was too dangerous. All of our experiences, knowing how these drugs work and what the toxicities are, would not seem to support that kind of conclusion. Noa is a pioneer in the use of these checkpoint inhibitors in myeloma. We have the opportunity to see and have remarkable things happen much earlier in the course of myeloma than most of these other things that we’ve been talking about or use.

Transcript edited for clarity.