Efficacy of TCE-Pomalidomide Salvage Therapy in RRMM

David Siegel, MD, hematologist-oncologist at John Theurer Cancer Center, Hackensack University Medical Center, discusses a retrospective single-center study evaluated the efficacy and safety of combining T-cell engager (TCE) therapies talquetamab (Talvey) or elranatamab (Elrexfio) with pomalidomide (Pomalyst) for patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). The research specifically focused on the potential for pomalidomide to "rescue" patients who had already progressed on or failed to respond to TCE monotherapy.

Study Overview and Methods

The study reviewed 16 patients at Hackensack University Medical Center treated between January 2024 and July 2025. This was a high-risk cohort:

• Prior Treatment: A median of 6 prior lines of therapy; 75% had received prior CAR-T therapy.
• Refractory Status: All patients were previously refractory to pomalidomide in other combinations.
• Cytogenetics: 68.7% exhibited high-risk cytogenetic features.

Key Findings

The results demonstrated that adding pomalidomide to a TCE can overcome established drug resistance:

• High Response Rates: The overall response rate for the entire cohort was 93.7%, with 62.5% achieving a very good partial response or better.
• Salvage Efficacy: Most significantly, for the 8 patients who showed no response to initial TCE monotherapy, the addition of pomalidomide resulted in an 87.5% salvage response rate.
• Speed of Action: The median time-to-response following the addition of pomalidomide was only 1 month.

Safety and Toxicity

While the combination was effective, hematologic management was necessary. Grade 3 or higher neutropenia occurred in 62.5% of patients, requiring dose adjustments in the majority of cases. However, the immunological safety profile was favorable: only grade 1 CRS) was reported, and no cases of ICANS occurred.

The study provides a clinical proof-of-concept that pomalidomide can reverse T-cell exhaustion and restore the efficacy of TCEs. Even in patients previously refractory to both pomalidomide and TCEs individually, the combination offers a highly effective salvage strategy for advanced RRMM.