Strategies for Treating Patients With Multiple Myeloma in Early Relapse

At the 2023 Great Debates & Updates in Hematologic Malignancies Meeting in New York, New York, Joseph Mikhael, MD, MEd, City of Hope Cancer Center, Phoenix, Arizona, shared his insights into the optimal strategies for treating patients with multiple myeloma (MM) in early relapse.

Transcript:

Hello, my name is Dr. Joseph Mikhael. I am a hematologist and a professor at the Translational Genomics Research Institute and the Chief Medical Officer of the International Myeloma Foundation.

It's a real privilege for me to be chairing the myeloma sessions today. In particular, I will be discussing how we approach patients with early relapse. Despite the great advances we've had in multiple myeloma and frontline therapy, we know that eventually literally all patients do relapse. 

Typically, we think of relapse in 2 categories: those in the earlier phases of relapse, typically 1 to 2 or 3 prior lines of therapy, and then those who are at later relapse. My good friend and colleague Dr [Saad] Usmani [Levine Cancer Institute, Charlotte, NC] will be addressing the issue of late relapse [at the meeting].

As we think about early relapse, there are a few key principles that I discuss in my talk that I think are worth reviewing, the first of which is that we don't so-called “save the best for last,” that we know that what we do earlier in myeloma therapy does have a significant impact in the long term. Just like selecting the right frontline therapy, we want to select the right earlier relapse therapies to give our patients the deepest and most durable remissions possible. 

Thankfully, we're informed by a whole series of phase 3 clinical trials to help guide that decision. Principle number 1, don't save the best for last. Let's use the best that we have, typically as a triplet combination.

Principle number 2, we want to select what is going to match the best option for patients, meaning we look at patient issues, such as their own comorbidities, their own preferences, and match that with therapy issues. Do we have therapies that are oral, that are intravenous, that are subcutaneous, that require a lot of intense visits or maybe less intense visits? 

Then, of course, disease-related factors, be it high-risk or standard risk or how quickly they've relapsed after initial therapy. Based on those 3 phenomena, we can match all of these great options we have with, indeed, the patient, so that they get the best personalized approach.

Then principle number 3 is really being able to know what all of those triplet combinations are. Typically, if a patient has not had a CD38 antibody in frontline therapy, we want to include that, and now we have 2 CD38 antibodies, daratumumab and cetuximab, that can be combined with carfilzomib, that can be combined with pomalidomide. There are 4 major trials right there, all of which can be given together to provide better outcomes for patients.

But also, we have a relatively new player in the field in early relapse in the form of selinexor as an XPO-1 inhibitor. It also now can be partnered based on a phase 3 study with bortezomib, but often we even partner it with carfilzomib or other options.

This lands us in a situation where what we select at first relapse becomes really important for the patient. But thankfully, we have a huge, deep bench of choice of all these different options. Understanding the nuances of each of them help us appreciate what is best for our patient.

To conclude, I always say, I don't treat myeloma, I treat people. When there are that many choices, it really is critical to center the patient in that discussion, to involve them, now that we have choice. In the older days when I treated myeloma 20 years ago, we didn't have much choice. But now that we have choice, it really is important to offer those different potentials to patients, to engage them and their care partners in the discussion so that we can treat patients in the best way possible.

Looking to the future, I do think that my talk would be very different in a couple of years from now as many of the things that are in the late relapse, CAR T-cell therapy, bispecific antibodies, are now going to be moving into the earlier relapse setting. As a clinician in the community practice, things are always moving. We want to inform individuals here at Great Debates & Updates what is not just the standard of care now, but what's coming in the near future.

Source:

Mikhael J. Making Sense of the Choices in Relapsed Myeloma. Presented at the Great Debates & Updates in Hematologic Malignancies Meeting; April 13-15, 2023; New York, NY.