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Investigating Talquetamab Plus Pomalidomide in the MonumenTAL-2 Study With Jeffrey Matous, MD

At the recent American Society of Hematology (ASH) Annual Meeting, Dr. Jeffrey Matous, MD, a Member of the Colorado Blood Cancer Institute in Denver, Colorado, presented his team's research and results of the MonumenTAL-2 trial, which studied talquetamab plus pomalidomide in patients with relapsed/refractory multiple myeloma. Dr. Matous then sat down with Oncology Data Advisor to further discuss his findings, the uniqueness of talquetamab in this setting, his team's next steps, and what to look forward to for the future of the MonumenTAL studies.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. Thank you so much for being here with us today, Dr. Matous.

Jeffrey Matous, MD: My pleasure.

Oncology Data Advisor: Would you like to start with a brief introduction of yourself and your research interests?

Dr. Matous: I'm Dr. Jeff Mattous and I am a Member of the Colorado Blood Cancer Institute in Denver, Colorado, and the Sarah Cannon Research Institute. I focus on plasma cell diseases, myeloma, amyloidosis, and Waldenstrom macroglobulinemia.

Oncology Data Advisor: To start off, what is the MonumenTAL-2 trial and what did it set to accomplish?

Dr. Matous: Great questions. The MonumenTAL-2 trial is an international trial looking at the drug talquetamab, which is a GPRC5D T-cell­–redirecting bispecific antibody in various combinations with different partners. It's looked both in the relapsed/refractory setting and also in the treatment-naive setting.

Oncology Data Advisor: What were the results that you presented?

Dr. Matous: We presented just one arm of the phase IB trial, combining talquetamab with pomalidomide. We enrolled patients who had a median of three prior therapies. Two or more prior therapies were required to enroll in the trial, including exposure to both a proteasome inhibitor (PI) and an immunomodulatory drug IMiD Patients could have been enrolled if they'd had prior pomalidomide as well. About a third of the patients had, and they could also have had prior T-cell–redirecting B-cell maturation antigen (BCMA) therapy; a minority of patients had that as well. They went on trial, and they all received talquetamab for the first month by itself with pomalidomide being added for Cycle 2.

The talquetamab dosing was just like on the FDA label. It could be either weekly or every other week. The pomalidomide dose began at 2 mg daily and investigators at their discretion could increase the dose to 4 mg daily later.

Oncology Data Advisor: How does including pomalidomide with talquetamab create an anti-myeloma synergy?

Dr. Matous: Theoretically, it's attractive because as we know, talquetamab works by recruiting T cells to the myeloma cell, and pomalidomide has many different immune effects, including recruiting immune cells to the cancer cell, decreasing immunosuppressive signals and so forth. IMID plus a bispecific antibody, I think that's a fabulous combination to explore, and we saw that in the results of the trial. When we look at the efficacy, we saw roughly 90% response rates, and in the patients with longer follow-up on the weekly dosing, two-thirds of those patients had complete responses and many of those had stringent complete responses. In my own practice, the patients that I have on this study, we have several patients in ongoing stringent complete responses beyond a year. So, I think that it's a potent combination and we've never seen a pomalidomide pair, if you will, that has resulted in this high efficacy rate.

Oncology Data Advisor: Since talquetamab is considered such a versatile therapy, are there any plans to evaluate its synergy with other regimens?

Dr. Matous: Yes, and part of the study that's ongoing there have been arms with lenalidomide or carfilzomib. The treatment-naive cohort is going to be talquetamab plus lenalidomide/daratumumab. I think that's very exciting as well. So, yes, this is a very, very active area of research.

Oncology Data Advisor: Final question that I had for you is with the results that you found with this study that you presented, what are the next steps for you and your team?

Dr. Matous: Well, I think it needs to go on to a broader study, including a randomized trial that's being contemplated in MonumenTAL-6. So, stay tuned for that. I think it's one of those things too where in the trial, I think we learned a lot in this study as well about how to manage the specific talquetamab side effects. I think that most clinicians might be familiar with dysgeusia nail findings, skin findings, and so forth. So, we've learned a lot, but I think there's no question in my mind that this combination is meritorious of further investigation for our patients.

Oncology Data Advisor: Definitely, and we're excited to hear more about MonumenTAL-6 in the future. Thank you so much for your time today, Dr. Matous. We appreciate it.

Dr. Matous: It was my pleasure.

About Dr. Matous

Jeffrey Matous, MD, is a Physician Member of the Colorado Blood Cancer Institute in Denver, Colorado, and the Sarah Cannon Research Institute. Dr. Matous is also a part of the Plasma Cell Disease Group. His research interest surrounds plasma cell diseases, myeloma, amyloidosis, and Waldenstrom macroglobulinemia, where he specializes and is an active participant in clinical studies working towards providing up-to-date and appropriate treatments for patients.

For More Information

Matous J, Biran N, Perrot A, et al (2023). Talquetamab + pomalidomide in patients with relapsed/refractory multiple myeloma: safety and preliminary efficacy results from the phase 1b MonumenTAL-2 study. Presented at: 2023 American Society of Hematology Annual Meeting. Abstract 1014. Available at: https://ash.confex.com/ash/2023/webprogram/Paper187706.html

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


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