Background: Talquetamab (Talq) is a GPRC5D and CD3 bispecific antibody approved for use in RRMM in pts previously treated with at least 4 lines of therapy, including a PI, IMiD, and CD38 monoclonal antibody. Data from the MonumenTAL-1 study showed an ORR of 63% at 11.8 median months of follow-up in pts previously receiving T-cell directed therapies (TCDT). CRS was noted in 77% of pts, and ICANS in 3% of patients receiving TCDT. Here, we present data further supporting the safety and efficacy of Talq in RRMM pts previously treated with TCDT. Methods: We performed a retrospective chart review with IRB approval to identify pts with RRMM previously receiving TCDT now receiving Talq. CRS and ICANS were graded per ASTCT consensus criteria, while responses were graded based on the IMWG response criteria. Results: 21 pts were evaluable for response, safety, and survival analyses. Median age was 64 years (range 39-89), 52.4% (n = 11) were male, and 23.8% (n = 5) had an ECOG PS ≥2. 61.9% (n = 13) had high risk cytogenetics (defined as del17, t(4;14), t(14;16)). Pts were heavily pretreated with a median of 7 (4-11) prior lines of therapy. 85.7% (n = 18) were triple-class refractory, and 57.1% (12) were penta-class refractory. 76.2% (n = 16) received prior CAR-T; 38.1% (n = 8) received prior Antibody Drug Conjugate (ADC);19.0% (n = 4) received both prior CAR-T and ADC. 9.5% (n = 2) of pts received prior tri-specific NK cell engagement therapies. 85.7% (n = 18) of patients in our study did not meet inclusion criteria for the MonumenTAL-1 study, including 38.1% (n = 8) for Hgb < 8.0, 28.6% (n = 6) for Plt < 50, 33.3% (n = 7) for EGFR < 40, 23.8% (n = 5) because of ECOG ≥2, and 42.9% (n = 9) for gene modified adoptive cell therapy within 3 months prior to Talq. With a median follow up of 2(1-5) months, OR and CR response rates were 71.4% (n = 15) and 28.6% (n = 6), respectively. Toxicity was comparable to the MonumenTAL-1 trial. CRS occurred in 57% (n = 12) of patients, (7 pts with grade 1, 5 pts with grade 2), with 23.8% requiring Tociluzumab. Median time to onset of CRS was 4 (1-7) days after the first dose, and median duration was 3.5 (1-10) days. 19.0%(n = 4) patients had ICANS, (1 pt with grade 1, 2 pts with grade 2, and 1 pt with grade 3). Infections were seen in 3 (14%) pts. 8 (38%) pts had treatment delays, mainly due to CRS, ICANS, and infections. 61.9% (n = 13), 28.6% (n = 6), and 76.2% (n = 16) of patients experienced skin AEs, nail AEs, or dysgeusia, respectively. 1 (4.8%) patient discontinued treatment after initial step-up dose due to ICANS and infection. There were no Talq related deaths. Conclusions: This single center study in pts with heavily pretreated and prior TCDTs demonstrated favorable ORR (71.4%) and CR (28.6%) rates, comparable to patients in the MonumenTAL-1 trial with and without exposure to prior T cell directed therapies. Results on PFS, OS, and AEs will be reported with continued follow up and will be presented in the meeting.