Talvey: A Promising Treatment for Relapsed/Refractory Multiple Myeloma

Multiple myeloma (MM) has long presented a formidable clinical challenge, particularly in the setting of relapsed or refractory disease. Though significant advances have expanded the therapeutic armamentarium over recent decades—with proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies targeting CD38—patients who have exhausted these established classes frequently face limited options, diminishing responses, and poor prognoses. A new promising option, a bispecific T-cell engager called talquetamab (brand name Talvey), can provide hope for some of these patients.

The quest for novel targets to treat multiple myeloma has led to the development of bispecific T-cell engagers, including agents that do not rely solely on B-cell maturation antigen (BCMA) as a target. Talquetamab has shown promise for patients with penta-refractory multiple myeloma, including those who have already progressed through anti-BCMA therapies.

“Talquetamab is a bispecific antibody that targets GPRC5D on multiple myeloma cells and has really shown to have unprecedented efficacy in patients with relapsed/refractory multiple myeloma. This drug [talquetamab] has been already approved, so it’s now available on a commercial basis,” Dr. Carolina Schinke, a hematologist/oncologist at the University of Arkansa, tells SurvivorNet Connect.

Clinical Efficacy: Data from the MonumenTAL-1 Trial

The phase 1/2 MonumenTAL-1 trial evaluated talquetamab in heavily pretreated patients with relapsed or refractory multiple myeloma. All patients had received at least three prior therapies, including the major drug classes mentioned above. The trial’s open-label, single-arm design allowed for the assessment of efficacy and safety in a real world-like refractory population.

Two dosing strategies were employed after initial “step-up” doses to mitigate severe cytokine release syndrome (CRS):

1. Once-Weekly Dosing (0.4 mg/kg):
Among patients naïve to T-cell redirection therapy, the overall response rate (ORR) was approximately 73% (95% CI, 63.2%-81.4%). At a median follow-up of 14 months, the median duration of response was 9.5 months. In a cohort previously exposed to other T-cell–redirecting therapies (including BCMA agents), the ORR was 72% (95% CI, 53%-86%). This is particularly noteworthy because responses to GPRC5D targeting were maintained despite prior exposure to and likely resistance against other bispecific or cell-based immunotherapies.

2. Every-Two-Weeks Dosing (0.8 mg/kg):
In patients naïve to T-cell redirection therapy, the ORR was 73.6% (95% CI, 63.0%-82.4%). After a median follow-up of six months, the median duration of response was not reached, and 85% of patients maintained their response for at least nine months.

These high response rates are especially encouraging given the refractory nature of the population. Talquetamab’s activity in both T-cell redirection-naïve and -exposed patients highlights its potential versatility. It can be considered either before or after BCMA-targeted approaches, depending on patient factors, prior therapy exposure, and clinical trial availability.

Safety Profile and Management of Adverse Events

Like other T-cell–engaging therapies, talquetamab can cause unique and sometimes severe adverse events. Early recognition and supportive care are critical to safe administration.

Dr. Schinke tells SurvivorNet Connect that research is indicating some side effects, like skin toxicity and taste toxicity, may be more severe for black patients than white patients — something to consider when weighing treatment options.

“There seems to be a trend of a little bit more toxicity in African Americans,” Dr. Schinke says. “Again, very small numbers [came from the trial data], but gives us an idea and I think further studies will be necessary to confirm these results.”

The most common side effects associated with the drug include:

1. Cytokine Release Syndrome (CRS)

CRS is one of the most common and important toxicities of T-cell redirectors. It typically manifests with fever, hypotension, hypoxia, and tachycardia. The incidence of CRS with talquetamab is significant but often low to moderate in severity, thanks partly to the step-up dosing schedule. Management generally involves supportive care, intravenous fluids, vasopressors if needed, and IL-6 inhibition (e.g., tocilizumab) for persistent or severe cases.

2. Neurotoxicity (ICANS)

Immune effector cell-associated neurotoxicity syndrome (ICANS) can present with confusion, cognitive dysfunction, or more severe neurological deficits. While less common than CRS, clinicians must remain vigilant. Prompt recognition and supportive measures, along with corticosteroids if indicated, are essential.

3. Oral Toxicities and Weight Loss

Talquetamab frequently causes oral toxicity, including dysgeusia, dry mouth, dysphagia, and stomatitis. Over 80% of patients in MonumenTAL-1 experienced oral toxicity, often mild but sometimes more severe. Such events can significantly affect nutritional intake and quality of life. Accompanying these oral issues, up to 62% of patients experience weight loss, with about 29% losing ≥10% of their baseline body weight. Proactive oral care, early nutritional support, hydration, and symptomatic management are vital.

4. Dermatologic and Nail Changes

Skin-related events are also common. Patients may develop maculopapular rashes, xerosis, pruritus, and nail dystrophy. These are usually grade 1 or 2 but can be distressing. Topical treatments, emollients, and prompt dermatologic evaluation can help manage these issues.

5. Infections, Cytopenias, and Hepatotoxicity

As with other advanced therapies for multiple myeloma, patients treated with talquetamab are at risk for cytopenias and infections due to their heavily pretreated state. Regular blood counts, vigilant infection prophylaxis, and monitoring of liver function are standard practices. Dose modifications may be needed for persistent cytopenias or significant liver enzyme elevations.