High Response Rates Noted in Anti–CD38-Refractory Myeloma With Talquetamab Plus Daratumumab Combo

Treatment with talquetamab (JNJ-64407564) and daratumumab plus hyaluronidase-fihj (Darzalex Faspro) resulted in durable, robust responses in heavily pre-treated multiple myeloma, primarily in patients who were refractory to anti-CD38 therapy, according to findings from the phase 1b TRIMM-2 study (NCT04108195).

Investigators reported an overall response rate (ORR) of 80.4% in the response-evaluable population (n = 51) after a median follow-up of 5.1 months. Moreover, patients who had prior anti-CD38 therapy exposure (n = 44) had an ORR of 77.3%. Among responders in the overall population, 15 (29.4%) had a complete response (CR) and 32 (62.7%) achieved a very good partial response or (VGPR) better. Patients who were treated with 400 μg/kg of talquetamab (n = 14) experienced an ORR of 71.4% at a median follow-up of 6.7 months. Moreover, in the 800 μg/kg group, the CR and VGPR rates within the group, respectively, were 29.7% and 35.1% and the ORR was 83.8%.

The trial included adult patients who had been diagnosed via the International Myeloma Working Group criteria who had at least 3 prior lines of therapy or were double refractory to a proteasome inhibitor or immunomodulatory drug. Patients were given 800 μg/kg of talquentamab every 2 weeks or 400 μg/kg weekly and subcutaneous daratumumab at an approved schedule of 1800 mg weekly for cycles 1 and 2, every 2 weeks for cycles 3 to 6, and subsequent monthly doses. Moreover, investigators used step-up dosing for talquentamab, with premedication being limited to step-up doses and the first whole dose of talquentamab.

In terms of other study findings, the time to first confirmed response was reported at 1.0 month in both cohorts. The median duration of response was not reached and 90.2% of patients with a response (n = 41) continued with treatment at a median follow up of 6.5 months.

In terms of safety, the most common grade 3/4 hematologic adverse effects (AEs) reported in the 400 μg/kg cohort included anemia (35.7%), thrombocytopenia (28.6%), neutropenia (28.6%) and lymphopenia (57.1%). Additionally, common grade 3/4 AEs in the 800 μg/kg cohort included anemia (18.2%), thrombocytopenia (15.9%), neutropenia (20.5%) and lymphopenia (15.9%).

Frequent any-grade nonhematologic AEs in the 400 μg/kg cohort consisted of dysgeusia (71.4%), dry mouth (71.4%), skin exfoliation (50%), pruritus (42.9%), headache (21.4%), back pain (21.4%), arthralgia (28.6%), cough (28.6%), dizziness (35.7%), nausea (35.7%), weight decrease (42.9%), decreased appetite (21.4%), and oropharyngeal pain (21.4%). In the 800 μg/kg cohort, the most common any-grade nonhematologic AEs included dysgeusia (59.1%), dry mouth (40.9%), skin exfoliation (29.5%), pruritus (22.7%), headache (25.0%), back pain (25.0%), arthralgia (20.5%), cough (20.5%), dizziness (18.2%), nausea (18.2%), weight decrease (15.9%), decreased appetite (20.5%), and oropharyngeal pain (20.5%).

Reference

van de Donk NWCJ, Bahlis N, Mateos MV, et al. Novel combination immunotherapy for the treatment of relapsed/refractory multiple myeloma: updated phase 1b results for talquetamab (a GPRC5D x CD3 bispecific antibody) in combination with daratumumab. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract S183.