(PA-513) Clinical Features and Management of GPRC5D related AE in Chinese Relapsed/Refractory Multiple Myeloma Patients Treated with Talquetamab: MonumenTAL-1 China cohort experience

Introduction:  Talquetamab (tal) is the first and only approved BsAb targeting novel antigen, GPRC5D. Tal has shown overall response rates of >70% in patients(pts) with relapsed/refractory multiple myeloma (RRMM) in the MonumenTAL-1 study. Efficacy and most safety data of China cohort had shown consistency with global cohort, but taste-related events were lower (25.0–41.1%) compared with global cohorts (71.0–72.0%). Here we report the clinical management of GPRC5D related AEs of MonumenTAL-1 China cohort.

Methods:   MonumenTAL-1 is a phase 1/2, open-label, multicenter study of tal monotherapy in RRMM pts. Phase 1 identified 2 RP2Ds, 0.4 mg/kg QW and 0.8 mg/kg Q2W, which were further assessed in phase 2. Chinese pts were enrolled in phase 2. CRS and ICANS were graded by ASTCT criteria; all other AEs were graded by CTCAE v4.03. Response was assessed per IMWG 2016 criteria.

Results:   29 pts were enrolled in 0.4mg/kg QW cohort and 12 pts were enrolled in 0.8mg/kg Q2W cohort. Updated median follow-up time was 16.3 mo and 13.9 mo respectively ORR was 69% and 67%, >=VGPR rate was 59% and 58%, >= CR rate was 38% and 58%. Median DOR was 15.7 mo and not reached. Median PFS was 8.3 and 10.7 mo, 12-month OS rate was 82.2% and 81.8% respectively.
GPRC5D “on-target, off-tumor” AE, included oral, skin and nail toxicities. The incidence of dysgeusia was 41% (12/29) in QW cohort and 25% (3/12) in Q2W cohort, median onset time was 15-17 days, median duration was 160-231 days, only 2 pts reported concurrent decreased appetite, and 4 pts reported concurrent >=10% weight decrease. 50%-58% dysgeusia was totally resolved at data-cut date Con-medication for dysgeusia including dexamethasone acetate, prednisone, olanzapine, riboflavin and Chinese herbal. Only 1 pts in Q2W cohort reported dry mouth. No pts had dose modification due to dysgeusia and dry mouth.
Skin AEs included rash and non-rash AEs. The incidence of rash was 38% and 25% respectively, with median onset time of 9-25 days and median duration of 17-23 days. Only 1 pts experienced grade 3 rash. Incidence of non-rash skin AEs were 52% and 42%, which included skin exfoliation, dry skin, and pruritus. Only 1 pts reported grade 3 event. Median onset time was 19-62 days, with a median duration of 28-40 days. Supportive care included topical moisturizers, topical corticosteroids, oral corticosteroids, oral anti-allergic medication and Chinese herbals. 79-100% rash were resolved, and 68-100% non-rash skin AEs were resolved. No event led to dose modification.
The incidence of nail disorders was 14% and 33% respectively, all grade 1/2, none lead to dose modification. Median onset time was 39-45 days, median duration of 223-301 days. Only 2 pts took topical paraffin and Vitamin E.

Conclusions:   Tal demonstrates deep responses in heavily pre-treated Chinese RRMM patients, with a clinically manageable safety profile. Clinical features of GPRC5D related AEs were similar to global cohort. No dose modifications were required to manage these GPRC5D related AEs in China cohort.