Talquetamab in R/R Myeloma: Key Insights from the MonumenTAL-1 Trial

As the therapeutic arsenal for relapsed/refractory multiple myeloma (MM) expands, the emergence of bispecific antibodies targeting GPRC5D offers a vital alternative for patients who have exhausted B-cell maturation antigen (BCMA)-directed therapies. The phase 2 MonumenTAL-1 trial (NCT04634552)¹ evaluating the bispecific T-cell engager talquetamab (Talvey) has demonstrated remarkable efficacy in a heavily pretreated population—including those with prior chimeric antigen receptor (CAR) T-cell exposure.

However, the clinical utility of talquetamab is uniquely defined by its toxicity profile. Unlike BCMA-targeted agents, which are often limited by high infection rates, talquetamab presents a distinct set of on-target, off-tumor toxicities, specifically involving skin, nail, and oral health. For clinicians, the challenge shifts from managing systemic immunosuppression to implementing proactive supportive care and patient education to ensure treatment adherence.

During a live Community Case Forum event in Huntington Beach, California, Amrita Krishnan, MD, explores the pivotal data from MonumenTAL-1, comparing talquetamab’s efficacy with current standards of care and detailing the practical strategies required to manage this new class of therapy effectively, from nutritional "bulking" to specialized nail care.

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Targeted Oncology: What were the study design and key efficacy and safety findings from the MonumenTAL-1 trial?

Amrita Krishnan, MD: The MonumenTAL-1 study design [involved the] same patient population as [MajesTEC-1; NCT04557098].² There's a weekly dosing and there's an every-2-week (Q2) dosing. They had a cohort who had prior T cell directed therapies [TCR]; median prior lines [was] 5, and in the cohort of prior T cell therapies, was 6 prior lines of [therapy], so [they were] pretty heavily pretreated patients. The response rates [ranged from] 69% to 70% even in the previous TCR group. In fact, they had a 67% response [rate], so that was also very encouraging to us.

In prior CAR T patients, looking at [progression-free survival; PFS], you can see [the] median PFS was about between 7.5 to 11 months. Duration of response, 17 to 19 months. Generally, we use the Q2 week dosing as our go-to approach. I don't think any of us have actually gone to the 1-week [dosing].

Here, the safety is a little different. Skin-related [adverse events; AEs] were 59%, nail-related [AEs] were 55%, [and] dysgeusia [AEs] were 72%, so it's a very different toxicity profile. [Rates of cytokine release syndrome were] pretty similar with that [of] the other bispecifics.

What practical strategies do you employ in your practice to manage off-tumor toxicities with talquetamab?

We actually have a handout that we give patients on [talquetamab AEs]. We tell patients to kind of bulk up before they even start [treatment] in terms of…gain[ing] weight [and]…maintain[ing] weight, especially to manage with the taste-related changes in the dry mouth. We tell patients [to use] clear nail polish, don't use your nails as tools to pick up things, [and to use] band aids if you feel like your nails are lifting off. A big part of this is educating the patient… We've tended to try and get them through [treatment] and then move on to dose and schedule changes, because I want patients to respond before I do this.

How can therapy with talquetamab be optimized to minimize the burden of toxicities on patients?

The biggest success for [talquetamab] is really working with your patient, working with your nurses and support staff to help manage these on-target, off-tumor toxicities. And if you can do that, then you can keep patients on because, again, the infection profile is significantly lower than BCMA-directed strategies.

A lot of us are starting to [conduct leukapheresis on] the patient, and then give talquetamab as a bridging therapy…In a way, it sort of aggregates some of the toxicity profile. And then patients go on to the BCMA CAR T. Now, we do have patients relapsing after BCMA CAR T… that's the next question for the future. The things we're doing now hopefully will be available soon widely, such as whole genome sequencing.

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REFERENCES

1.A study of talquetamab in participants with relapsed or refractory multiple myeloma (MonumenTAL-1). ClinicalTrials.gov. Updated January 16, 2026. Accessed February 24, 2026. https://clinicaltrials.gov/study/NCT04634552

2.A study of teclistamab in participants with relapsed or refractory multiple myeloma (MajesTEC-1). ClinicalTrials.gov. Updated February 13, 2026. Accessed February 24, 2026. https://clinicaltrials.gov/study/NCT04557098