P-027: Real World Experience of Standard of Care Talquetamab in Patients with Relapsed and Refractory Multiple Myeloma

Introduction: Talquetamab (Talq) is a GPRC5D bispecific antibody approved for triple class exposed patients (pts) with relapsed and refractory multiple myeloma (RRMM), after MonumenTAL-1 study demonstrated an ORR of 71.7% at a dose of 0.8mg/kg subcutaneous every 2 weeks (Q2W) after step-up doses. Here, we present data further supporting the safety and efficacy of Talq in RRMM pts.

Methods: This retrospective study at Moffitt Cancer Center evaluated pts with RRMM that were treated with standard of care (SOC) Talq at a dose of 0.8mg/kg subcutaneous Q2W after step-up doses between September 2023 and May 15, 2024. CRS and ICANS were graded per ASTCT consensus criteria, while responses were graded based on the IMWG response criteria.

Results: A total of 39 pts was treated with Talq in our institution; 30 pts with intent to treat until disease progression or intolerable adverse events, and 9 pts with intent to bridge to CAR-T with only 1 cycle of therapy. Median age was 65 years (range 39-89), 46.2% (n=18) were male, and 20.5% (n=8) had an ECOG PS ≥2. 69.2% (n=27) had high risk cytogenetics (defined as del17, t(4;14), t(14;16), and gain 1q).

Pts were heavily pretreated with a median of 7 (4-11) prior lines of therapy. 92.3% (n = 36) were triple-class refractory, and 48.71% (n=19) were penta-class refractory. 71.8% (n=28) received prior B-cell maturation antigen targeted therapies (BCMA-TT). 51.3% (n=26) of pts did not meet inclusion criteria for the MonumenTAL-1 study, including 35.9% (n = 14) for cytopenia, 20.5% (n=8) for renal dysfunction, and 15.4% (n=6) for ECOG ≥2. With a median follow up of 5.7 (1-9) months, progression free survival (PFS) and overall survival (OS) has not been reached. Overall response rate was 76.9% (n=30) with 12 pts (30.77%) achieving a complete response or better (≥CR). Ten pts (25.6%) achieved minimal residual disease (MRD) negativity by next generation sequencing (NGS). ORR was 66.7% (n=20/30) among pts receiving Talq as primary treatment and 88.9% (n=8/8) among those receiving Talq as bridging.

Toxicity was comparable to the MonumenTAL-1 trial. CRS occurred in 53.8% (n=21) of pts, (12 pts with grade 1, 8 pts with grade 2, and only 1 pt with grade 4), with 25.6% (n=10) requiring Tocilizumab. Median time to onset of CRS was 4.9 (1-10) days after the first dose. 15.4% (n=6) pts had ICANS, (3 pts with grade 1, 2 pts with grade 2, and 1 pt with grade 3). Infections were seen in 11 (28.2%) pts. Dysgeusia, weight loss, skin-related changes, and nail-related were seen in 79.5% (n=31), 43.6% (n=17), 64.1% (n=25), 43.6% (n=17) of pts respectively. Pts bridged with Talq had more skin-related changes, but less dysgeusia than those primary treated, but weight loss was comparable.

Conclusions: This single center real world safety and efficacy analysis was comparable to that reported in the MonumenTAL-1 study. Longer follow up and larger numbers are needed to properly understand the role of Talq as bridging therapy for CART.