At the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, Jeffrey V Matous, MD, Sarah Cannon Research Institute, Colorado Blood Cancer Institute, Denver, Colorado, shared expert insight on initial trial results of a GPRC5D and CD3-targeted therapy, talquetamab, and an immunomodulatory drug (iMid), pomalidomide for patients with relapsed/refractory (R/R) multiple myeloma (MM).

These initial safety and efficacy results from the MonumenTAL-2 study demonstrated that talquetamab plus pomalidomide showed rapid, deep responses among patients with R/R MM and ≥2 prior lines of therapy.

Transcript:

My name is Dr. Jeffrey Matous. I'm a member of the Colorado Blood Cancer Institute in Denver, Colorado. We're also part of the Sarah Cannon Research Institute. Today, I'd like to present for ASH 2023, the results of our phase 1b study [that is] examining, for the first time, the combination of an [immunomodulatory drug] (IMiD) and talquetamab in the treatment of patients with relapsed/refractory multiple myeloma, specifically pomalidomide and talquetamab. This is part of the MonumenTAL-2 study, which studies several different combinations of different agents along with talquetamab, which as I think [as] most of us know, is a [G protein–coupled receptor, class C, group 5, member D] (GPRC5D) redirecting T-cell antibody, which is already FDA approved. In this study, we enrolled 35 patients who had received at least 2 prior regimens for their relapsed/refractory myeloma, including a [proteasome inhibitor] (PI) and an IMiD. We also allowed patients who had received prior [B cell maturation antigen] (BCMA) directed therapies to go in the study as well. 

[I]n the study, patients had a median of about 3 prior regimens, up to 15, and 2 dose levels of the talquetamab were explored. About 16 patients had the weekly dosing of talquetamab and [an] additional 19 were accrued with every other week dosing of talquetamab. With respect to the pomalidomide, [it] was added with cycle 2 and at a dose of 2 milligrams daily. Then, investigators had the option if they desired to increase that dose from 2 milligrams to 4 milligrams. About half [of] the investigators actually tried to do that, and we'll discuss what the implications of that were in a little bit of time. Patients were treated until progression of side effects dictated otherwise. The talquetamab schedule remained as it is, although after a while, patients could all transition to monthly dosing of the talquetamab. 

In terms of efficacy, the regimen was really, I think, clinically very active, and I think the most clinically active partner with pomalidomide that we've ever seen. Approximately 90% of patients had responses to the combination [and] responses were quick, as one might expect, and the responses were durable. Most patients who responded were responding at 6 months or beyond. Of these responses, about 2/3 of them in the weekly dosing, which has longer follow-up, by the way, had stringent complete response or better, which I think [is] fabulous and really [an] unprecedented response for this population of patients outside of CAR T-cell therapy. For the patients with every other week dosing, their complete responses so far are fewer in number [at] about 36%. But again, those patients have shorter follow-ups as well. Now, what about the tolerability? 

All of us are interested in tolerability, especially because talquetamab has unique side effects of dysgeusia, skin rash, nail findings, and so forth. What we found [are] those typical side effects of dysgeusia [were] occurring in virtually all subjects who were treated. Primarily because of that, about ¾ of patients had doses held of talquetamab during the course of the study. About 45% of the patients had dose modifications; modifications either of the dose or the schedule of talquetamab on the study. With respect to [cytokine release syndrome] (CRS), [it] was seen as before in about ¾ of patients, and as before as well, these were mostly grade 1 events in about almost half of patients [who] received tocilizumab [at] the discretion of the investigators. The pomalidomide required dose modification in about 1/3 of patients. Many of those patients who had dose modifications were after attempts had been made to raise the dose of pomalidomide from 2 to 4 milligrams, [which is] something to keep in mind as we go forward with this combination. Regarding discontinuations, they are very rare. About only 4 patients of the 35 discontinued, which I think is very encouraging as well. Overall, I'd say what we have here is a combination of an IMiD, pomalidomide, and a GPRC5D redirecting CAR T-cell therapy, talquetamab, that looks extraordinarily efficacious so far with rapid response, responses which are durable, and with tolerability that I would categorize as manageable or acceptable. I think this forms a baseline for taking this combination forward in further investigations.

Source:

Matous J, Biran N, Perrot A, et al. Talquetamab + pomalidomide in patients with relapsed/refractory multiple Myeloma: Safety and preliminary efficacy results from the phase 1b monumenTAL-2 study. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 1014