Talquetamab/Pomalidomide Shows Deep Responses in R/R Multiple Myeloma

Combining talquetamab-tgvs (Talvey) with pomalidomide (Pomalyst) demonstrated enduring responses among patients with relapsed/refractory multiple myeloma, according to findings from the phase 1b MonumenTAL-2 study (NCT05050097) presented in a poster session at the 2025 American Society of Hematology (ASH) Annual Meeting and Exhibition.¹

Data showed an objective response rate (ORR) of 85.7% (95% CI, 69.7%-95.2%), which included a very good partial response (VGPR) or better rate of 80.0% as well as a complete response (CR) or better rate of 45.7%. The rates of PR, VGPR, CR, and stringent CR were 5.7%, 34.3%, 11.4%, and 34.3%, respectively. All patients with prior exposure to CAR T-cell therapy (n = 3/3) and pomalidomide (n = 8/8) achieved a response.

Talquetamab/pomalidomide produced a median duration of response (DOR) that was not evaluable (NE; 95% CI, 12.5-NE), with a 12-month DOR rate of 71.1% (95% CI, 50.3%-84.4%). Additionally, the median progression-free survival (PFS) was 25.8 months (95% CI, 12.9-NE), with 44.8% (95% CI, 26.5%-61.4%) achieving PFS at 36 months.

Other data showed that B cells were sustained across the first several cycles of therapy. These reports were comparable with prior findings and supported the B-cell–sparing mechanism of talquetamab.

“With longer follow-up, talquetamab [plus] pomalidomide continued to elicit deep and durable responses in patients with relapsed/refractory multiple myeloma, consistent with previously reported analyses. The combination of [talquetamab/pomalidomide] demonstrated a clinically manageable safety profile, consistent with individual agents, with no new safety signals identified with longer follow-up,” lead study author Hang Quach, MD, MBBS, FRACP, FRCPA, professor of hematology at the University of Melbourne and departmental head of clinical hematology and clinical hematology research at St Vincent’s Hospital Melbourne, wrote with coauthors in the poster.¹ “These findings continue to support the phase 3 MonumenTAL-6 study [NCT06208150], which compares the efficacy of [talquetamab plus pomalidomide] vs investigator’s choice of elotuzumab [Empliciti] plus [pomalidomide and dexamethasone] or [pomalidomide plus bortezomib (Velcade) and dexamethasone] in patients with [relapsed/refractory multiple myeloma] who had 1 to 4 prior lines of therapy.”

In the phase 1b MonumenTAL-2 study, patients were assigned to receive talquetamab at 0.4 mg/kg every week (n = 16) or 0.8 mg/kg every 2 weeks subcutaneously (n = 19) in combination with pomalidomide. Treatment with pomalidomide began in cycle 2 on days 1 to 28 of each cycle at 2.0 mg orally each day, with dose escalation to 4.0 mg daily permitted.

The trial’s primary end point was safety. Key secondary end points included ORR, time to response, DOR, and PFS.

Patients with measurable multiple myeloma, at least 2 prior lines of treatment including a proteasome inhibitor and lenalidomide (Revlimid), and an ECOG performance of 0 or 1 were eligible for enrollment on the trial. Those with prior bispecific antibodies, CAR T-cell therapy, and pomalidomide were eligible for study entry; those with prior GPRC5D-directed treatment were ineligible.

The median patient age was 65 years, and the median number of prior lines of treatment was 3. Additionally, 45.0% of this cohort had high-risk cytogenetics, and 20.0% had extramedullary disease. Patients had prior exposure to agents such as pomalidomide, BCMA-directed CAR T-cell therapy, and bispecific antibodies.

The most common hematologic adverse effects (AEs) of any grade and grade 3/4, respectively, included neutropenia (68.6%; 65.7%), anemia (42.9%; 31.4%), and thrombocytopenia (31.4%; 22.9%). The most common any-grade and grade 3 or higher non-hematologic AEs included infections or infestations (85.7%; 31.4%), cytokine release syndrome (74.3%; 2.9%), skin-related toxicity (74.3%; 5.7%), nail-related events (68.6%; 0%), and dry mouth (57.1%; 0%).

Dose reduction of talquetamab and pomalidomide due to AEs occurred in 25.7% and 48.6% of patients, respectively. Additionally, 65.7% and 80.0% required dose omissions due to toxicity, and 77.1% and 22.9% required dose delays due to AEs. Investigators noted no additional discontinuations of any study therapy due to AEs since an initial report of 8.6%, which suggested the absence of cumulative toxicity.

In the multi-center phase 3 MonumenTAL-6 trial, an estimated population of 795 patients will be assigned to receive talquetamab plus pomalidomide, talquetamab plus teclistamab-cqyv (Tecvayli), or elotuzumab plus pomalidomide/dexamethasone or bortezomib/dexamethasone.² The trial’s primary end point is PFS. Secondary end points include ORR, the CR or better rate, overall survival, time to next treatment, health-related quality of life, and safety.

References

1. Quach H, Perrot A, Matous J, et al. Talquetamab, a GPRC5D×CD3 bispecific antibody, in combination with pomalidomide in patients with Relapsed/Refractory multiple myeloma: Updated safety and efficacy results from the Phase 1b MonumenTAL-2 study. Blood. 2025;146(suppl 1):2282. doi:10.1182/blood-2025-2282
2. A study comparing talquetamab plus pomalidomide, talquetamab plus teclistamab, and elotuzumab, pomalidomide, and dexamethasone or pomalidomide, bortezomib, and dexamethasone in participants with relapsed or refractory myeloma who have received an anti-CD38 antibody and lenalidomide (MonumenTAL-6). ClinicalTrials.gov. Updated December 5, 2025. Accessed December 8, 2025. https://tinyurl.com/2tacpycx