Earlier this year, Dr. Sarah Holstein of the University of Nebraska Medical Center participated in a two-part continuing medical education (CME) activity regarding practice-changing strategies and improved patient outcomes in the treatment of multiple myeloma (MM). With many updates and improvements in the treatment of MM since recording, Dr. Holstein joins OncData to share her knowledge and talk about what to look forward to from this year's ASH Annual Meeting.

Oncology Data Advisor: Welcome to Oncology Data Advisor, a digital resource for the multidisciplinary cancer team. Today I am joined by Dr. Sarah Holstein of the University of Nebraska Medical Center. Earlier this year, she recorded a two-part continuing medical education (CME) activity regarding practice-changing strategies and improved patient outcomes in the treatment of multiple myeloma. Today she is here to update us on improvements since recording, as well as share a bit of what to look forward to from this year's ASH Annual Meeting.

Good morning, Dr. Holstein. Thank you again for joining me today to talk about this important subject. Would you like to introduce yourself and talk a bit about your research interests first?

Sarah Holstein, MD, PhD: Sure. My name is Sarah Holstein, I'm a Professor at the University of Nebraska Medical Center in the Division of Oncology and Hematology. I am a specialist in multiple myeloma and other plasma cell disorders. From a research perspective, my research interests really span the entire translational clinical spectrum, so I have a laboratory focused on new drug development. From a clinical research perspective, I'm interested in the incorporation of novel drugs into the treatment of myeloma.

Oncology Data Advisor: Incredible. Thank you for that. Recently you recorded an activity with us to talk about practice-changing strategies and improved patient outcomes in treatment of multiple myeloma, so I wanted to ask you, have there been any updates regarding treatment or outcomes from clinical trials that you mentioned in the activity or at all that you would like to talk about?

Dr. Holstein: Myeloma remains a swiftly moving field, and there have been a lot of things that have happened in the last year, in terms of new drug approvals and at least one drug being removed from the market. In the newly diagnosed setting, I think that we've had further confirmation of benefit of adding daratumumab into the newly diagnosed, transplant-eligible induction setting. We've had some more recent data presented on the Griffin study showing longer-term follow-up and showing a suggestion of progression-free survival benefit for incorporation of daratumumab upfront. I think that's continuing to shape treatment practices for that patient population. I would say the most prominent changes have really occurred in the relapsed/refractory setting, where some of the agents that we talked about that were under development have now been FDA-approved. We have a second CAR T-cell product, ciltacabtagene autoleucel (Carvykti™⁾, that was approved in 2022, another BCMA CAR T-cell product. We also now have a BCMA bispecific agent, teclistamab, that's recently been approved.

We're now really learning how to incorporate those into our treatment of the relapsed/refractory patient, particularly those patients who've had four or more prior lines of therapy. One of the agents that we did spend time talking about was belantamab mafodotin, which is an antibody-drug conjugate against BCMA, and unfortunately, that has just very recently been withdrawn from the market, after it failed to show benefit in a phase 3 confirmatory study. Again, things are moving swiftly, and I predict that there are going to be even more changes in treatment paradigms in the relapsed/refractory setting as we move ahead.

Oncology Data Advisor: From all the recent approvals and updates and everything, have there been any trials that you've personally participated in that you would like to talk more in depth about?

Dr. Holstein: I think some of the work that is ongoing is interesting and some of it's going to be presented at this upcoming American Society of Hematology (ASH) conference. One of the agents that's currently under investigation has a novel mechanism of action and is termed modakafusp alfa. It's an immunocytokine, so it's a first-in-class anti-CD38 monoclonal antibody that's conjugated to attenuated interferon. I think it's really interesting, because it has activity in disease that's refractory to the commercially available anti-CD38 monoclonal antibodies and it really appears to have a unique mechanism of action. That's one of the new treatments that's away from the BCMA field right now, which is really crowded, but clearly we need non-BCMA targeted therapies. Our center has been participating in that study, really, since the phase 1 portion of it. I think some updated results from the phase 2 cohorts will be presented at ASH.

There's actually an ongoing randomized portion that's expanding, looking at two different dose levels, that hopefully will lead the way to eventual FDA approval, that we're currently participating in as well. I would say, otherwise, at our center, we are heading up a maintenance study looking at iberdomide, which is one of the novel cereblon E3 ligase modulation drug (CELMoD) agents, which is being heavily investigated in multiple myeloma.

We're looking at it in patients who have undergone a transplant and are using it as a maintenance therapy. This study is ongoing, so we don't yet have results, but again, at ASH I think there's going to be some updated data from iberdomide in the context of relapsed/refractory studies as well as data on another CELMoD, mezigdomide, that will be presented at ASH. Again, those agents, I think, are really interesting, because they're going to have the potential to be incorporated not only in the late lines of therapy and earlier lines of relapsed/refractory, but also potentially induction and maintenance.

Oncology Data Advisor: I was going to ask you about the upcoming ASH meeting, because we're really looking forward to it and learning more about it. I know you just mentioned a lot of what you're looking forward to and what you'll be presenting. Is there anything else you would like to mention from ASH that you're looking forward to maybe?

Dr. Holstein: Just on my initial purview of the abstracts so far, I think there's a lot of exciting work, both on the basic science front, in terms of trying to understand mechanisms of resistance to some of the therapies that we're currently using from an immune perspective, but there are also really interesting phase 1 clinical trials that are going to be presented. I think there are some novel CAR T products that either use novel manufacturing processes or novel targets that I think are going to be really interesting and might give us a hint as to what the future might entail, once we get beyond our currently used first-generation CAR T products.

There's going to be, I think, an entire oral session devoted to bispecific antibodies. Clearly, it's going to be a huge field of myeloma. Again, we already have one recently approved agent, teclistamab, but there are many other BCMA-directed bispecifics as well as bispecifics going after other targets that I think have great potential for the treatment of myeloma. Again, other agents with novel mechanisms of action are being investigated. It's always really interesting to take a peek at the preclinical setting, to see what's on the horizon, and I think there's a lot of good stuff being presented there as well.

Oncology Data Advisor: Definitely. We're super excited to hear about it. Why do you believe it is important that the health care team stay up-to-date on novel treatment options for multiple myeloma?

Dr. Holstein: Myeloma, again, is a disease whose treatment strategies are changing so incredibly rapidly. The more options we have, the more complicated it gets. The newer options are associated with some unique toxicities. Certainly, in an era where we're really concerned about infections, we really need to understand the data. I think understanding what the new agents are, how to use them, and when to use them is really critical. I think having somebody as part of the team that is a specialist in myeloma is incredibly important, because it's our job to keep up on all of this.

I think it's otherwise incredibly difficult for those team members who are also treating patients with all the other types of malignancies to keep up-to-date. It feels like, sometimes, our treatment paradigms are changing even within 6 months to 12 months. Again, it can be a little bit disconcerting to see the list of new agents in the relapsed/refractory setting grow and grow, but I think as we continue to learn about these agents, there will continue to be improvement in our understanding as to how to sequence these agents and how to get the best outcomes. Being up-to-date on all of that will hopefully improve patient outcomes, which, at the end of the day, is the most important thing.

Oncology Data Advisor: Final question I have for you, going off what you were just saying, would you have any advice to the health care team in myeloma to stay motivated to stay up-to-date and maybe some tips and tricks on how to make it not so overwhelming?

Dr. Holstein: I'm not sure I have a perfect answer for that. I would say, these days, that patients, of course, are incredibly savvy and are learning about things. You want to make sure that when a patient comes in and has seen something, whether it's something from ASH or something online, that you're aware of what they're talking about. There's always that motivation to make sure that you're as up-to-date as the patients that you're treating. I think if you're a community oncologist, having a good relationship with the myeloma specialist or CAR T or transplanter at your nearest center is really important, and that understanding the recommendations that those specialists make will help guide your practice.

I always encourage the community oncologist I work with to have little hesitation in calling me or texting me or emailing me to run patients by them, because, again, I recognize that I have the luxury of only concentrating on this disease 100% of the time and that others don't have that luxury. Ultimately, if we're going to be able to safely use these new agents or to use new combinations, we really need to understand the safety profile and the data. Again, not to sound like a broken record, but ultimately it's all about providing the best outcome for our patients.

Oncology Data Advisor: Definitely. It's good to repeat that as much as possible. We definitely appreciate it, and we appreciate you, for your research and keeping us updated as well. Thank you so much for your time today, Dr. Holstein.

Dr. Holstein: Thank you.

About Dr. Holstein

Sarah Holstein, MD, PhD, is a Professor in the Division of Hematology and Oncology at the University of Nebraska Medical Center. Dr. Holstein's practice and research revolve around multiple myeloma, including newly diagnosed, relapsed/refractory, and diagnoses in the post-transplant maintenance setting. She participates in multiple national multiple myeloma committees and serves as a member of the International Myeloma Working Group.

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.