Safety results from REALiTAL: A multi-country observational retrospective study of talquetamab in patients with relapsed/refractory multiple myeloma outside of clinical trials

Abstract Introduction: Talquetamab is the first approved bispecific antibody targeting GPRC5D and CD3 for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). With a median follow-up of over 30 months, the pivotal phase I/II MonumenTAL-1 (N=375) trial showed an overall response rate of ≥66.7% across all cohorts. Median duration of response was 9.5 months (every week [QW]) and 17.5 months (every-other-week [Q2W]). Median progression-free survival was 7.5 months (QW) and 11.2 months (Q2W). Common adverse events (AEs) in MonumenTAL-1 included cytokine release syndrome (CRS), taste-related AEs, and non-rash skin-related AEs. REALiTAL is a retrospective non-interventional study of patients receiving talquetamab outside of clinical trials, with the majority of patients included as part of pre-approval access programs. Topline efficacy and safety data have been published previously. Here, we report further in-depth safety data from the REALiTAL study. Methods: Eligible patients provided informed consent and received the first dose of talquetamab on or before December 31, 2023. Data, including baseline characteristics, prior therapies, and safety information, were collected from medical records. Safety data included incidence and severity of CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and GPRC5D-related AEs. AEs were graded by CTCAE v4.03. CRS and ICANS were graded by ASTCT criteria. Results: Overall, 93 eligible patients were included in REALiTAL across 26 sites in 7 countries. Median follow-up was 15 (Range, 0.4–25.3) months. Patients were heavily pretreated, with a median of 5 (range: 2–16) prior lines of therapy. Almost all patients (97.8%) were triple-class exposed, and most (86.0%) were penta-class exposed. Fifty-seven (61.3%) patients had previously received BCMA-targeted therapies. The most common treatment-emergent AEs were CRS (55.9%), infections (47.3%), skin/nail toxicity (67.7%), and oral toxicity (66.7%) including dysgeusia (57%). CRS was mostly grade 1/2; 1 (1.1%) patient had a grade 3 event. Twenty-two (23.7%) patients received tocilizumab for CRS, including 1 as prophylaxis. All but 1 CRS event resolved or was resolving at data collection. There were 2 (2.2%; both grade 1) cases of ICANS. One patient reported a grade 3/4 nervous system disorder; no ataxia/balance disorders were reported. Forty-two (45.2%) patients received immunoglobulin replacement, 35 (37.6%) as primary prophylaxis for infection and 4 (4.3%) as secondary prophylaxis. Overall, 44 (47.3%) patients had an infection; 8 (8.6%) were grade 3/4, and only 1 (1.1%) patient discontinued due to infection (septic shock). Skin and nail AEs occurred in 63 (67.7%) patients; all were grade 1/2 except 1 (1.1%) grade 3 AE. Thirty-three (35.5%) patients received treatment for skin and nail toxicities, 2 (2.2%) as prophylaxis. Four (4.3%) patients interrupted talquetamab due to skin and nail AEs, but none discontinued. Twenty-six (28%) patients received treatment for oral toxicities, 2 (2.2%) as prophylaxis. Oral toxicity occurred in 62 (66.7%) patients, mostly grade 1/2 with 1 case of grade 4 stomatitis that did not lead to discontinuation. Two (2.2%) patients interrupted study drug, 1 (1.1%) reduced dose, and 1 (1.1%) discontinued due to oral toxicities. Seventy-five percent of skin and nail toxicity events and 58% of oral toxicity events resolved or were resolving at the time of data collection. There were 8 (8.6%) deaths, none were considered related to talquetamab. Conclusions: AEs in REALiTAL were clinically manageable, with no new safety signals identified. CRS was mostly low grade and resolved, with limited use of tocilizumab in the study. Oral and skin toxicity was reversible with most events improved. Rates of serious infections were low, and few patients discontinued treatment due to GPRC5D-related AEs, with just 1 discontinuation due to dysgeusia. Overall, the safety profile of talquetamab was consistent with that observed in MonumenTAL-1.