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2024-09-23T13:18:51.000Z

Frontline quadruplet therapy for multiple myeloma: Update from SOHO 2024

Sep 23, 2024
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Learning objective: After reading this article, learners will be able to cite a new clinical development in multiple myeloma.

Quadruplet therapies combining anti-CD38 monoclonal antibodies, a proteasome inhibitor, an immunomodulatory agent, and dexamethasone in sequence with ASCT lead to deep and durable responses in NDMM.1 A review of outcomes in patients treated with upfront quadruplet therapies was presented at the Society of Hematologic Oncology (SOHO) 2024 Annual Meeting by Ajay Nooka.1

Key learnings:

The phase III PERSEUS (NCT03710603) trial demonstrated deep and durable responses with daratumumab + VRd compared with VRd in patients with transplant-eligible NDMM.

Real-world findings and long-term results from the CASSIOPEIA trials confirmed the benefit of daratumumab-based quadruplet therapies in NDMM.

Isatuximab + VRd demonstrated improved post-induction MRD negativity compared with VRd in the GMMG-HG7 (NCT03617731) trial.

The phase III IMROZ (NCT03319667) and BENEFIT (NCT04751877) trials demonstrated that quadruplet therapies can improve the depth of response and lead to high rates of MRD negativity. This translated into a 63% 5-year PFS benefit for isatuximab + VRd vs VRd in the IMROZ study.

Benefits of upfront quadruplet therapies in high-risk disease were demonstrated in the MASTER (NCT03224507) and GMMG-CONCEPT (NCT03104842) trials, and for transplant-ineligible elderly patients in the ALCYONE trial (NCT02195479). 

These findings suggest upfront quadruplet therapies as the preferred SoC for transplant-eligible and transplant-ineligible patients. The depth of response and high PFS rates offer the potential for improved disease control, delaying relapse.

ASCT, autologous stem cell transplantation; MRD, measurable residual disease; NDMM, newly diagnosed multiple myeloma; PFS, progression-free survival; SoC, standard of care; VRd, bortezomib + lenalidomide + dexamethasone.

  1. Nooka A. Session VI: Multiple Myeloma. Frontline therapy – Quads for everyone? Society of Hematologic Oncology (SOHO) 2024 Annual Meeting; Sep 4-7, 2024; Houston, US.

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