Unanswered Questions on Sequencing Talquetamab for RRMM

Jonathan L. Kaufman, MD

David Bankes Glass Multiple Myeloma Professorship

Professor, Department of Hematology and Medical Oncology

Emory University School of Medicine

Medical Director and Section Chief, Ambulatory Infusion Centers

Winship Cancer Institute of Emory University

Atlanta, GA

DISCUSSION QUESTIONS

• What is your reaction to the phase 1 MonumenTAL-1 (NCT03399799/NCT04634552) efficacy and safety data in patients with relapsed/refractory multiple myeloma (RRMM)?​
• How does the efficacy, e.g. degree and duration of response for talquetamab (Talvey), compare with other standards of care in RRMM?

SUKHMANI GILL, MD: It’s impressive. When we…talk about picking [talquetamab] over other available treatments, I'm still not sure, in terms of sequencing, whether it would make me necessarily pick this, but I think it's impressive, and I think that it definitely has its place in the treatment of patients. Future studies will hopefully tell us a little bit more about sequencing.

ANUSHA MADADI, MD: [Talquetamab] definitely has good efficacy, but again, sequencing is always the question. I don't know with [only] phase 1 data.

SANDEEP PANDIT, MD: I think it has impressive response rates. [GPRC5D] seems to be a very good target to go after, because it's present in almost all of the plasma cells. The serious cytokine release syndrome [CRS] rate seems to be very low.¹ Plus, there is about a 70% overall response rate [ORR] in patients who have had BCMA [B-cell maturation antigen]-directed therapies. It seems very impressive, and it brings up the question about sequencing. It could be used after [targeting] BCMA, and then can we come back and use another BCMA-targeted agent after this? This would probably give us that option. Those questions come to mind.

PETER MANCUSI-UNGARO, MD: I had not seen the data previously. The toxicity of GPRC5D therapy is bothersome and makes one think [you should] exhaust BCMA therapy before proceeding to it. If you get a better survival, then it makes sense to put up with the toxicity and proceed to the alternative target. I don't know the answer to any of those questions [on sequencing].

CHARLES KUZMA, MD: I was aware of the data, but talking to some of my key opinion leaders at the universities to whom I refer my patients with RRMM, anecdotally, I hear that the toxicity is very tough with the weight loss, dysgeusia, and the skin and nail [toxicity].

DICUSSION QUESTION

• Do you feel the adverse events with GPRC5D bispecifics (e.g. talquetamab), although different in nature from the BCMA bispecifics, are less toxic, more toxic, or similar in nature?

SREEDHAR KATRAGADDA, MD: I would say less toxic because BMCA [targeting is associated with] more infections. Those are the toxicities that kill people. Dry mouth, nail changes, and skin changes are not life threatening. Also, it has impressive data in patients with prior CAR [chimeric antigen receptor] T-cell therapy, a [65%] overall response rate.¹

KWABENA OSEI-BOATENG, MD: We know that with talquetamab, patients had received previous BCMA-[targeted therapy]. But…with the BCMA bispecific T-cell engagers and with CAR T-cell therapy, patients hadn't had previous GPRC5D-targeted treatments.

KAUFMAN: That goes to the sequence [question].… One of the challenges in teasing apart sequencing is, whenever you put something after something, then that patient had 1 more line of therapy, and their multiple myeloma figured out how to overcome this, so it became more resistant overall. Teasing those apart is hard, and that's why the types of studies that cooperative groups do [are] asking these questions. [They are not just asking], “Is this drug better than standard of care,” but “How should we practice? What is the right thing to do?” Because if we think we're going to use both of these drugs, then let's design a study where we use both of these drugs and we figure out the right sequence for an individual patient.

_Reference:

_{1. Touzeau C, Schinke C, Minnema M, et al. PIVOTAL phase 2 MonumenTAL-1 results of talquetamab (TAL), a GPRC5DXCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). HemaSphere. 2023;7(S3):e5955094. doi:10.1097/01.HS9.0000967676.59550.94}