Data presented at the 2022 ASH Annual Meeting suggest new therapeutic options may be on the horizon for patients with relapsed or refractory multiple myeloma (MM) and patients with newly diagnosed, high-risk or ultra-high-risk MM. 

Results from the phase 1/2 MonumenTAL-1 trial suggest the bispecific antibody talquetamab can provide deep and durable responses for patients with relapsed/refractory MM.1 

Early data from the phase 1b MajesTEC-2 trial suggest that combining teclistamab, daratumumab, lenalidomide, and dexamethasone may be safe and effective for MM patients who received 1-3 prior lines of therapy.2 

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Results from the phase 2 OPTIMUM/MUKnine trial suggest that extended and intensified consolidation with daratumumab, bortezomib, lenalidomide, and dexamethasone after autologous transplant may improve outcomes for patients with ultra-high-risk MM.3 

And results from the phase 2 GMMG-CONCEPT trial showed that combination isatuximab, carfilzomib, lenalidomide, and dexamethasone produced high rates of minimal residual disease (MRD) negativity in both transplant-eligible and -ineligible patients with high-risk, newly diagnosed MM.4

MonumenTAL-1: Talquetamab Demonstrates Activity in Heavily Pretreated MM

Talquetamab, a bispecific antibody targeting GPRC5D on MM cells and CD3 on T cells, demonstrated efficacy in patients with relapsed/refractory MM in the phase 1/2 MonumenTAL-1 trial ( Identifiers: NCT03399799, NCT04634552).1 

In the phase 1 portion of the trial, researchers identified 2 recommended phase 2 doses of subcutaneous talquetamab: 0.4 mg/kg weekly and 0.8 mg/kg every other week (Q2W). A total of 288 patients received these doses — 143 at 0.4 mg/kg weekly and 145 at 0.8 mg/kg Q2W. In both dose groups, the patients had received a median of 5 prior lines of therapy (overall range, 2 to 17). 

In the weekly dosing group, the median follow-up for efficacy was 14.9 months. The overall response rate (ORR) was 74.1%, 9.8% of patients achieved a complete response (CR), and 23.8% achieved a stringent CR (sCR). The median duration of response was 9.3 months overall, and it was not reached for patients who achieved a CR/sCR. The median progression-free survival (PFS) was 7.5 months. 

In the Q2W dosing group, the median follow-up for efficacy was 8.6 months. The ORR was 73.1%, 12.4% of patients achieved a CR, and 20.0% achieved an sCR. The median duration of response was 13.0 months overall, and it was not reached for patients who achieved a CR/sCR. The median PFS was 11.9 months. 

The rate of cytokine release syndrome (CRS) was 79.0% in the weekly dosing group and 72.4% in the Q2W group. There were 13 cases of immune effector cell-associated neurotoxicity syndrome (ICANS) in the weekly group and 11 cases in the Q2W group. In both groups, 4 patients had grade 3 CRS, and 4 had grade 3 ICANS. There were no cases of grade 4 CRS or ICANS. 

Other common adverse events (AEs) in both dosing groups were infections, dysgeusia, skin-related AEs, nail disorders, anemia, neutropenia, lymphopenia, and thrombocytopenia. There were 2 deaths due to COVID-19, 1 in each group.

The researchers also looked at patients from both dosing groups who had received T-cell redirection therapy prior to study entry. In this group, the ORR was 62.7% overall, 72.2% in patients with prior chimeric antigen receptor T-cell therapy, and 44.4% in patients with prior bispecific antibody treatment. Overall, the CR rate was 5.9%, and the rate of sCR was 17.6%. At a median follow-up of 11.8 months, the median duration of response was 12.7 months. AEs in this group were similar to those seen in each individual dosing group.

Ajai Chari, MD

“The drug is very active, including for patients who have exhausted all available therapies,” said study presenter Ajai Chari, MD, of Mount Sinai School of Medicine in New York, New York. 

“I think talquetamab will probably be the next drug approved in the relapsed or refractory setting and the first drug for the GPRC5D target,” said Urvi A. Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, who was not involved in this trial.