TRIMM-2 Study Shows Efficacy in R/R Multiple Myeloma

Multiple Myeloma: Multiple MyelomaNew data from the TRIMM-2 Phase Ib clinical trial highlight the potential of a three-drug combination therapy for patients with relapsed or refractory multiple myeloma (RRMM). The trial explored the efficacy and safety of talquetamab, an innovative GPRC5D-targeting bispecific antibody, in combination with daratumumab and pomalidomide. The results presented at the 2024 International Myeloma Society (IMS) Annual Meeting show the therapy offers significant clinical benefits in a population that has often exhausted multiple lines of treatment (Abstract OA-01). The TRIMM-2 trial enrolled 77 patients with heavily pretreated RRMM, most of whom had received at least three prior therapies, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies. Notably, 77.9 percent of the participants were classified as triple-class refractory, meaning they were resistant to these major drug classes. The median time since diagnosis was 6.8 years, and many patients had previously undergone chimeric antigen receptor T-cell therapy or bispecific antibody treatments. Patients in the study received talquetamab at two dosing regimens—either 0.4 mg/kg weekly or 0.8 mg/kg every 2 weeks—alongside subcutaneous daratumumab and oral pomalidomide starting from the second cycle. The study monitored the treatment's efficacy and safety with adverse events categorized according to standardized criteria. Study Results The results showed a high overall response rate of 81.8 percent with more than half of the patients (53.2%) achieving a complete response or better. The median duration of response was 22.1 months, while the median progression-free survival reached 15.5 months. These responses were particularly notable in patients who were refractory to daratumumab or pomalidomide, as well as those who had previously undergone T-cell redirection therapies. The median time to achieve a first response was just 1 month, demonstrating the rapid action of the combination. Additionally, the durability of response in this heavily pretreated population, with many cases of resistance to previous therapies, underscores the potential of this novel approach. Adverse events were common, though most were manageable and consistent with those seen in prior studies of the individual drugs. The most frequent side effects included dysgeusia (79.2%), neutropenia (77.9%), and cytokine release syndrome (CRS) (74.0%). Nearly all cases of CRS were mild to moderate, resolving within 2 days after the onset. Infections were also prevalent, affecting 74.0 percent of patients, with 29.9 percent experiencing Grade 3 or 4 infections. Importantly, the study reported no dose-limiting toxicities. However, two Grade 5 adverse events were observed (sepsis and hemorrhagic stroke), underscoring the need for careful patient monitoring. Overall, 5.8 percent of patients discontinued the treatment due to side effects. Conclusions & Future Directions “The deep and durable responses shown in these latest results from TRIMM-2 further support the potential of [talquetamab] in combination with [daratumumab-pomalidomide], which has become a standard of care in multiple myeloma,” stated Nizar Bahlis, MD, Associate Professor in the Arnie Charbonneau Cancer Institute at the University of Calgary and the study's presenting author. “With high overall response rates seen across cohorts, this combination shows potential for significant disease control and survival in patients who have received multiple lines of prior therapy, including exposure to prior bispecific antibodies.” Bahlis, who also serves as an Associate Professor of Medicine in the Hematology and Bone Marrow Transplantation division at the University of Calgary, emphasized the need for further studies to evaluate this combination in broader patient populations and refine dosing strategies to optimize outcomes. The promising results presented at the IMS Annual Meeting offer a strong rationale for continued research into talquetamab-based regimens. These findings reinforce talquetamab's versatility as a combination therapy in multiple myeloma treatment and bring renewed hope for patients with limited treatment options. Dibash Kumar Das is a contributing writer. Read more articles on hematology/oncology online at https://tinyurl.com/see5pf32

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