Personalizing Therapies for Optimal Outcomes in Multiple Myeloma

Paul Richardson, MD

How clinicians choose to sequence treatment for patients with multiple myeloma to provide a more personalized approach has played an important role in managing this disease over time. According to Paul Richardson, MD, treating multiple myeloma is never a “one-size-fits-all” approach, so it is important to tailor treatments for each patient.

“Multiple myeloma is a highly heterogeneous disease. It's full of multiple subgroups of patients. In that context, the ability to have rational combination strategies that integrate small molecule approaches, immune therapies, transplantation and so forth, is an absolutely vital way forward,” said Richardson, Clinical Program Leader of the and Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center, and institute physician at Dana-Farber Cancer Institute, as well as the RJ Corman professor of Medicine at Harvard Medical School, in an interview with Targeted Oncology^TM.

When choosing between the available regimens for patients with multiple myeloma, experts look at the disease characteristics of patients, including stage, age, kidney function, response to prior therapies, and more, to create this more personalized approach and improve the quality-of-life of patients.

In the interview, Richardson highlighted his presentation from the 4th Annual Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies on updates and personalization of treatments for patients with multiple myeloma.

Targeted Oncology: Can you discuss the importance of personalizing treatments for patients with multiple myeloma?

Richardson: It was my privilege to present this [topic] at the fourth meeting, led by Guenther Koehne, MD, PhD. It was an outstanding meeting and I'm very grateful to the organizers for inviting me. My remit was to frame the immune rationale or the immune therapy rationale in myeloma and contextualize it in the incredibly exciting environment we have with multiple treatment options for our patients, recognizing the promise of immune therapies, and at the same time, recognizing the value of backbone approaches that have continued to provide benefit.

The overarching thrust of my presentation was to share that this is never a case of one-size-fits-all, but rather all hands to the pump. We need all the tools that we're fortunate enough to have. Multiple myeloma is a highly heterogeneous disease. It's full of multiple subgroups of patients. In that context, the ability to have rational combination strategies that integrate small molecule approaches, immune therapies, transplantation and so forth, is an absolutely vital way forward.

What are some of the currently available options for patients with multiple myeloma?

In the upfront space, triplets are established as a standard of care. That involves a proteasome inhibitor, an immunomodulator, and a steroid. Now, we have the quadruplets where that exact same platform is integrated with a monoclonal antibody classically targeting CD38. In this case, daratumumab [Darzalex] has led that charge. Isatuximab [Sarclisa]is coming up behind, but nonetheless, I think it offers real value, particularly in the relapse setting.

Why is it impoartnt to personalize treatments for patients with multiple myeloma?

Basically, tailoring therapy to frailty to access, to minimize hospitalization, and to improve quality of life, all of these factors become important. Given that this platform is so highly active, I think it is very exciting and great that we could [tailor treatments].

Is there any ongoing research in this space that has recently caught your eye?

[I must] acknowledge the incredible advances from immunotherapy platforms and my colleagues who have led those efforts. We've seen tremendous excitement around bispecifics, we've seen tremendous excitement around chimeric antigen receptor [CAR] T, but also, [it is important] to recognize that behind that requires other approaches that are perhaps more practical, perhaps a little easier to operationalize, and these are equally valuable, in my opinion, because we have to be able to provide to our patients who are frail, elderly, perhaps on minority communities in which hospitalization is much less attractive, we may need to be able to move these new opportunities into the clinics in an absolute sense, ie become truly community based. I think that's in the future, and I think it will happen with some of the very exciting immunotherapies.

But right now, we have oral options that could also address that, as well as infusional ones that are relatively straightforward to administer, and are clearly clinically beneficial. I think amongst the oral options, we must focus on talking about the emerging excitement around CELMoDs and how useful those are. It's been my privilege to research mezigdomide [CC-92480], a particular agent that is attracting attention because it's oral and it seems to work very well, even in the face of triple-class refractory and quad refractory or BCMA-exposed disease. For patients this is an exciting way forward.

For the community oncology audience, what recommendations would provide to those treating patients with multiple myeloma?

I would offer one of continued hope, but also one of continued excitement around the novel therapies that are increasingly available. Also, understand that this complexity is understandable, and you can make sense of it. I think for some of my community oncologists, they get a little dazzled and sort of think, what do we do next? I would simply say, you can think through a paradigm now of proteasome inhibition, immunomodulation, CD38 targeting, BCMA targeting, and then how you can revisit these classes of drugs, recombine them, look at newer agents, such as the CELMoDs, such as bispecifics, and CAR T therapies, and the appropriate patient.

At the same time, also recognize that in some patients, there may be value to autologous stem cell transplant with high-dose melphalan flufenamide [Pepaxto] or newer approaches that seek to try and emulate that. I think there are a variety of takeaways that are important, and I am also excited by some of the ongoing work with immunoconjugates and antibody approaches that are simple and relatively easy to give.