Introduction: Talquetamab (TAL) is a GPRC5D targeting bispecific antibody approved for the treatment of relapsed refractory multiple myeloma. Herein we report the results of real-world experience of TAL from seven international institutions
Methods: Patients were enrolled and consented in an IMWG retrospective protocol; patients treated with TAL outside of a clinical trial from Jan 2023 through March 2024 were eligible
Results: 101 patients were included in this analysis. The median age was 64, median LOT was 6, 92% (58/63) were triple drug refractory and 49% (38/77) were Penta refractory. The median number of immunotherapies before TAL was 2 (range 1,4) and 74% received prior anti-BCMA therapy, 49% (n=51) would not have been eligible for TAL clinical trial due to exclusion criteria, 21% (14/65) had an ECOG of 2 or greater, 76% (38/50) had high risk cytogenetics, one had plasma cell leukemia and seven had extra medullary disease.
84% (83/99) received TAL as an inpatient with a median hospitalization of 10 (0,37) days. CRS during Step up Dose (SUD) 1 was present in 33% (32/97) Gr 1 (56%), Gr2 (9%), Gr 3 (6%), CRS during SUD 2 was present in 35% (33/94), Gr 1 (66%), Gr 2 (9%), CRS during SUD 3 was present in 23% (15/65), Gr 1 (80%), Gr 2 (6%) and with first full dose was 14% (13/95), Gr 1 (69%). ICANS occurred in 7% (7/99), Gr 1 (14%), Gr 2 (28%), Gr 3 (14%).
Non hematological toxicities included skin toxicity presented as rash, dryness, itching and peeling in 80% (57/71), Gr 1 (68%), Gr 2 (28%), Gr 3 (4%), with 8% (3/36) needing dose interruptions. Nail toxicity occurred in 43% (20/47), Gr 1 (75%), Gr 2 (25%) with 10% needing dose interruptions. Dysgeusia was present in 65% (51/78), Gr 1 (49%), Gr 2 (49%), Gr 3 (2%) with 17.6% (n=6/34) needing dose interruptions. Oral toxicity including stomatitis, glossitis, ulcerations, or dry mouth occurred in 69% (34/49), Gr1 (71%), Gr 2 (23%), Gr 3 (6%) with 16% (5/32) needing dose interruptions. Infections after starting TAL at any timepoint occurred in 49% (34/69) of patients, with CMV reactivation in 19% (10/53).
Response rates will be reported at the time of presentation.
Conclusions: The RWE of TAL in a heavily pretreated population including those with prior immunotherapy has a similar toxicity and safety profile to the clinical trial experience, with the exception of higher rates of dysgeusia and CMV reactivation. This may be in part due to a higher proportion receiving prior immunotherapy thereby accounting for higher rates of CMV subsequently. The high incidence of oral toxicity and dysgeusia described here suggests that optimal management of these side effects is key in maintaining patients on TAL.