From Research to Practice: New Treatment Modalities for Patients With Multiple Myeloma

Ryan Haumschild, PharmD, MS, MBA, CPEL, vice president of ambulatory pharmacy at Emory Healthcare Winship Cancer Institute, provided valuable insights into the evolving treatment modalities in multiple myeloma (MM) at the Oncology Pharmacists Connect 2024 meeting. In the interview, Haumschild discusses advancements in new treatment approaches, the effectiveness of combination therapies, overcoming treatment resistance, and management of common adverse effects associated with new lines of treatment.

Pharmacy Times: Can you discuss the evolving treatment modalities in MM and how do these new treatments compare with traditional approaches in terms of efficacy and patient outcomes?

Ryan Haumschild: So, in myeloma, we've seen a lot of changes recently. And so that's been exciting innovation for our patients, not only new therapies, but the way we're combining the different treatment options. So historically, everyone becomes transplant or transplant, ineligible, either standard or high risk. And we'd start with maybe a double [inaudible]. And then from there, do some combination therapies depending on [the] mutation and resistance that would occur. We are still looking at transplant eligible and non-transplant eligible, but really innovating. We're bringing more effective therapies up earlier and lines of treatment. So instead of waiting for relapse refractory to introduce some different treatments, now we're saying, “what do we do if we move that earlier?” So now starting maybe triplets or quadruplets in the frontline setting, introducing innovative combinations earlier, such as bispecifics now looking at cell therapies, and we move those up in earlier lines of therapies. And we're doing that all because we know plasma cell disorders are more of a disease without a cure. But as we have more of these durable responses, patients are living longer, healthier lives, having even longer progression-free survival and better overall response rates.

Pharmacy Times: What are some of the most effective combination therapies currently being used for multiple myeloma, and how do they enhance treatment outcomes?

Haumschild: Yeah, so some of the effective treatment options that we're seeing, in my opinion, are just introducing it in earlier lines of therapy and using synergistic or complementary mechanisms of action. So, if I think about it in the frontline setting, we're going to have more of a CD38, probably with an immunomodulator agent [sic], and then probably produce some inhibitor and dexamethasone—really hitting a quadruplet in the front line. And we're seeing data emerge [when] do triplet or quadruplet. And I think there's data to make a decision on both. I think, too, is we sequence [and] then we go into different therapies, right? So, have we tried a different type of proteasome inhibitor? Have we tried a different combination therapy? Do we introduce CD38s later and lines of therapy. And then come the innovative bispecifics and fellow therapies that many of us have started to utilize. And how do we see clinical trials now introducing bispecifics in combination with some of these therapies, and even earlier lines of treatment? And so that's where the future's headed, that's where the combinations are continuing to evolve and change. And with that comes more improved efficacy, the introduction of improved MRD, and then, lastly, enables us to sequence our therapies and even later lines of treatment.

Pharmacy Times: How do these advanced therapies overcome treatment resistance MM and improve long-term outcomes for patients?

Haumschild: I really think it's utilizing synergistic treatment approaches that overcome resistance in labor lines of treatment. And so, we want to get that most durable response early on. And that's something that we get really excited about. But we need to pivot as patients maybe progress on therapy or start to show signs and symptoms. And with that, we utilize things like a bispecific, where it's attacking to different areas and different targets. And it could be a BCMA targeted bispecific, and patients will respond really well. But then we even have GPRC5D, so alternative, [mechanism of action–]bispecifics that can be utilized later in lines of treatment. And again, we're doing that for the sole reason to continue to get strong response rates into later lines of treatment. And I think by utilizing all those complementary mechanisms of action, leveraging the latest data that we're seeing coming out of ASH, and ASCO, I think that's how we're staying ahead of this disease, and really treating these plasma cell disorder patients in the most efficacious fashion possible.

Pharmacy Times: What are the most common side effects associated with the new treatment modalities, and how can they be managed?

Haumschild: Yeah, when we think about traditional side effect profiles, we think about gastrointestinal issues, we may think about neutropenia as and peripheral neuropathies. But now, as we've introduced more cell therapies, car T [and] bispecifics, we have to be concerned about cytokine release syndrome [CRS], and neurotoxicity, and ICANS. And so, I think those are new, emerging side effect profiles that we're aware of. We've managed cell therapy for a while, but I think with bispecifics, we're seeing less CRS, but maybe delayed CRS. And so how are we getting ahead of it? We're looking at pre-treatment options, looking at developing outpatient infrastructure, like an Intermediate Care Center where those patients can arrive and be treated and evaluated in a timely manner. And I think those are the new side effect profiles that we're concerned about. And then, just lastly, how do we internally develop a risk stratification based on patient fit status, prior treatment, underlying toxicity, to make sure they're appropriate for those treatments as well? And I think that's what we're looking at as we move forward, especially as we move some of these innovative treatments into earlier lines of therapy.

Pharmacy Times: How might these research findings translate into new standards of care for multiple myeloma patients in the near future?

Haumschild: I think the research is coming out constantly and I think the standard-of-care continues to evolve. There's not a day I don't go on Twitter or read a post on ASCO about different treatment approaches that are emerging, how some are leveraging antibody drug conjugates, or some are looking at bispecifics and earlier lines, or they're adopting a cell therapy that might be a BCMA approach. And then maybe looking at a bispecific BCMA. It is their data there. And so, I think that's really the exciting piece to me is we're not just reserving these durable responses in these high overall response rates until later lines, we're moving them into earlier lines. And at the same time now, we're not just looking at some of these traditional efficacy endpoints, but we're including MRD. We're starting to look at how are they with [MRD]? And is that giving them an upfront response, where we can mitigate or minimize some of that maintenance therapy as we move forward?

Pharmacy Times: What are the key challenges that need to be addressed to bring these new treatments from research to clinical practice?

Haumschild: So, I think that the key challenges to me is we got to continue to generate evidence, we've got to continue to anchor towards MRD, and how we utilize that not just as an exploratory endpoint, but as a decision-making endpoint. I don't think we're there yet. But I think we're continuing to build that evidence to move it forward. And I think, too, with some of these innovative therapies, how do we make sure that we can operationalize them? Like we had with by specifics, making sure that we can do step -up doses? And I think, in a fashion, that's not just always impatient dependent. How do we get data on whether patients been exposed to bispecific can they have data and still have a good response rate to another vice specific or from cell therapy to by specific or bridging with bispecifics? So, in my opinion, it's just developing more of this evidence. And I think, ultimately, that's going to lead to the bench to bedside translation of clinical innovation.

Pharmacy Times: What initiatives or programs are in place to keep patients and healthcare providers informed about the latest treatment advancements?

Haumschild: So, when we think about the latest treatment advances, a lot of professional societies, I think of Oncology Pharmacists Connect, I think of American Society of Hematology, I think about the American Society of Clinical Oncology, who are bringing forward different data. But I also think that there's clinical trial data that comes forward. And when you're part of that NCI-designated comprehensive cancer center network, there's a lot of clinical trials that providers can be aware of innovative research that's going on— phase 1, phase 2 data, how to get involved, how to enroll patients. And in my opinion, that's one of the best ways that we can recognize where the unmet needs are, work together collaboratively with our patient populations, and kind of bring forward some of the latest treatments. And then lastly, leveraging clinical guidelines, consortium groups around different endpoints like MRD, from exploratory to practical integration, and I think that's really how we're going to move the needle forward for our patients and our providers.