The 2024 International Myeloma Society (IMS) Annual Meeting in Rio de Janeiro showcased significant progress in multiple myeloma treatment, with several trials reporting promising results. These advancements span novel combinations, improved minimal residual disease (MRD) negativity rates, and enhanced survival outcomes, offering new hope for patients across various disease stages.
Novel Combinations Show Deep and Durable Responses
Updated findings from the phase 1b TRIMM-2 study (NCT04108195) revealed that the combination of talquetamab-tgvs (Talvey), daratumumab with hyaluronidase-fihj (Darzalex Faspro), and pomalidomide (Pomalyst) induced deep and durable responses in patients with relapsed/refractory multiple myeloma. The overall response rate (ORR) reached an impressive 82%, indicating the potential of this triplet therapy in heavily pre-treated patients.
Daratumumab Plus VRd Improves MRD Negativity
The phase 3 CEPHEUS trial (NCT03652064) investigated the addition of subcutaneous daratumumab to the VRd regimen (bortezomib [Velcade], lenalidomide [Revlimid], and dexamethasone) in newly diagnosed multiple myeloma patients ineligible for or deferring transplant. Results demonstrated a statistically significant improvement in MRD negativity rates compared to VRd alone, with a complete response rate or better at 81.2% vs 61.6% with VRd (OR, 2.73; 95% CI, 1.71-4.34; P < .0001). This suggests daratumumab's potential to deepen responses and improve long-term outcomes in this patient population.
CAR T-cell Therapy Reduces Risk of Death
Updated results from the phase 3 CARTITUDE-4 trial highlighted the survival benefits of ciltacabtagene autoleucel (cilta-cel; Carvykti). Treatment with this chimeric antigen receptor (CAR) T-cell therapy reduced the risk of death by 45% compared to standard of care in patients with lenalidomide-refractory multiple myeloma and at least one prior line of therapy. This underscores the transformative potential of CAR T-cell therapy in relapsed/refractory myeloma.
Bispecific Antibodies Show Promise in Triple-Class Exposed Disease
Findings from the phase 1b RedirecTT-1 study (NCT04586426) indicated that the combination of talquetamab plus teclistamab-cqyv (Tecvayli) delivered a high rate of durable responses in patients with triple-class exposed relapsed/refractory multiple myeloma. This suggests that bispecific antibodies can provide meaningful benefit in patients with limited treatment options.
Refining Treatment Strategies Based on MRD Response
The phase 3 AURIGA study (NCT03901963) focuses on patients with minimal residual disease (MRD)–positive, newly diagnosed multiple myeloma in the post-transplant setting, examining daratumumab combined with lenalidomide. These findings will help refine treatment strategies based on MRD responses, potentially leading to more personalized treatment approaches for patients.
