ASH 2025 | Real-world outcomes of talquetamab for RRMM: US Multiple Myeloma Immunotherapy Consortium

So at this year’s ASH, I will be presenting work on real-world outcomes of patients with relapsed/refractory multiple myeloma who received talquetamab as standard of care. This is a project that was done as part of the U.S. Immunotherapy Consortium. So we know that talquetamab is a GPRC5D bispecific antibody that has shown very promising results in the pivotal MonumenTAL-1 study with overall response rate varying between 65 and upwards of 70% in the different cohorts, which median progression-free survival of about 7.5 months and overall survival of 11.2 months. But there’s really very little real-world data out there to say how these patients are doing in the real world. So what we did, we did a study with the Immunotherapy Consortium that includes 15 centers in the U.S. And we included all patients who got standard of care talquetamab between 2023 and 2025. So overall, we included 484 patients. Median age was 66 years. Overall, patients were heavily pre-treated with more than 50% of patients having had at least six prior lines of treatment. Approximately 90% were triple-class refractory, and half the patients were penta-refractory, and 70% of patients received a prior autologous transplantation. Furthermore, about 70% of patients included in our cohort would have been ineligible for the MonumenTAL-1 study. Our cohort was also enriched in patients with high-risk characteristics. So this included about 65% of patients who had high-risk cytogenetic abnormalities and approximately a third of patients had high tumor burden in baseline bone marrow evaluation. Also included about 25% of patients with true extramedullary disease. So looking at how talquetamab was administered, so we saw that most patients, about 84% of patients, starting cycle two, a dosing regimen of 0.8 milligrams per kilo every two weeks was used. And in a minority of patients, a different dosing regimen was used, such as 0.4 milligrams per kilo weekly in 6%, and less so with other regimens such as 0.8 milligrams per kilo every four weeks. In 6% of patients, an additional drug was used together with talquetamab. So this included mostly daratumumab or pomalidomide. These were usually added early on in the course of talquetamab treatment. Median duration of treatment of talquetamab was around 100 days, so just over three months. Importantly, 21% of patients, so 101 patients, overall received talquetamab as bridging prior to BCMA CAR-T. Those patients received talquetamab for a median of 29 days. Looking at safety outcomes, so overall, cytokine release syndrome, CRS, was observed in about 47% of patients, mostly low grade, although there was one fatal event of CRS, grade 5. Overall, neurotoxicity, that’s ICANS, was observed in just under 15% of patients. Again, mostly low grade. Overall, 40% of patients had an infection during the follow-up, mostly viral and bacterial, although there were some fungal infections as well. Most patients, over half of the patients, received IVIG while receiving the talquetamab. Usually started at around day 30 after the start of talquetamab. And 5% of patients did require ICU during the first cycle. Looking at the unique toxicities to talquetamab, these are the on-target off-tumor events. So oral toxicity was observed in almost 80% of patients. Skin toxicity, so rash or skin irritation, just over 50%. And nail toxicity was observed in 41%. Eight patients developed invasive second primary malignancies while receiving talquetamab. Overall, we observed 157 cases of deaths in our cohort, mostly due to disease progression, less so due to infections while on talquetamab. Looking at efficacy outcomes, the overall response rate in our cohort was 72.5% with 46.6% VGPR or better. The responses were overall observed very early as evidenced by 64% response at day 30. Responses were overall deep and within the cohort of patients who had evaluable MRD data, 65% of the patients achieved MRD negativity at best response, both when we looked at MRD as examined by flow, and also when we looked at the cohort of patients who had the clonoSEQ data available. Survival outcomes, so median progression-free survival for the entire cohort was 7.8 months, with a 12-month PFS rate of just under 40%. Median overall survival was not reached with a median follow-up of just under a year. 12-month overall survival rate was 63%. When we did multivariable analysis, we identified some variables that were associated with reduced progression-free and overall survival. These included both trial ineligibility and true extramedullary disease. On the other hand, two variables that were associated with better survival outcomes, both PFS and overall survival were having a BMI above 30 and use of talquetamab as bridging towards CAR-T. For the patients who received talquetamab as bridging for CAR-T, the median progression-free survival and overall survival were not reached. On the other hand, for patients who received talquetamab but did not proceed with CAR-T after talquetamab, the median progression-free survival was quite low at 6.5 months, and median overall survival was also lower at 15.7 months. So to conclude, in this large real-world analysis of 484 patients who received talquetamab for relapsed/refractory multiple myeloma, overall response rate and progression-free survival were overall similar to what was observed in the MonumenTAL-1 study, that even though approximately 70% of the patients would have been ineligible to that clinical trial. Patients who received talquetamab as bridging prior to CAR-T had much better outcomes, both in terms of progression-free and overall survival. And rates of toxicities were also overall similar to what was observed in MonumenTAL-1, including more than 70% of patients who developed dysgeusia.

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