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Multiple myeloma (MM) remains a challenging hematologic malignancy, particularly for transplant-ineligible patients. Recent advancements in treatment protocols aim to improve these patients’ outcomes and quality of life. The Phase 3 IMROZ study, presented by Prof. Thierry Facon and colleagues at the ASCO Annual Meeting, evaluates the efficacy and safety of a novel combination therapy: isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd), compared to the standard VRd regimen. This abstract sheds light on promising new therapeutic strategies and underscores the importance of optimizing treatment for better patient outcomes.

Multiple myeloma is a cancer of plasma cells that often affects older adults. Standard treatment for newly diagnosed multiple myeloma (NDMM) typically includes a combination of bortezomib, lenalidomide, and dexamethasone (VRd). However, not all patients are eligible for stem cell transplantation due to age or comorbidities. For these patients, finding effective and tolerable treatment regimens is crucial.

Isatuximab is an anti-CD38 monoclonal antibody that induces myeloma cell death through multiple mechanisms, including antibody-dependent cellular cytotoxicity and direct apoptosis. Its addition to the standard VRd regimen (creating Isa-VRd) aims to enhance therapeutic efficacy without significantly increasing toxicity.

The IMROZ study (NCT03319667) is a global, prospective, randomized, open-label Phase 3 trial designed to compare the efficacy and safety of Isa-VRd versus VRd in transplant-ineligible NDMM patients. Patients were randomized 3:2 to receive either Isa-VRd or VRd, with the primary endpoint being progression-free survival (PFS). Key secondary endpoints included complete response (CR) rates, minimal residual disease (MRD) negativity, overall survival (OS), and safety profiles.

The study enrolled 446 patients from 102 sites across 21 countries. Patients were stratified by age, Revised International Staging System (R-ISS) stage, and geographic region (China vs. non-China). The Isa-VRd group received isatuximab (10 mg/kg IV), bortezomib (1.3 mg/m² SC), lenalidomide (25 mg PO), and dexamethasone (20 mg IV/PO), while the VRd group received the standard regimen without isatuximab.

The study’s findings are significant and promising:

  • Progression-Free Survival (PFS): At a median follow-up of 59.7 months, the median PFS was not reached for the Isa-VRd group, compared to 54.3 months for the VRd group (HR 0.596, p=0.0005). This indicates a substantial reduction in the risk of disease progression or death by 40.4% with Isa-VRd.
  • Complete Response (CR) and MRD Negativity: The Isa-VRd group showed higher CR rates (74.7% vs. 64.1%) and MRD negativity (55.5% vs. 40.9%) compared to the VRd group, highlighting deeper and more sustained responses.
  • Safety Profile: The safety profile of Isa-VRd was consistent with the addition of isatuximab, with no significant increase in grade 3 or higher adverse events. The most common adverse events were manageable, and the overall tolerability was acceptable.

The IMROZ results have several critical implications for clinical practice:

  1. New Standard of Care: The significant improvement in PFS and deeper responses with Isa-VRd suggests this combination could become a new standard of care for transplant-ineligible NDMM patients.
  2. Enhanced Treatment Efficacy: Adding isatuximab to the VRd regimen provides a potent therapeutic option that significantly reduces the risk of disease progression and enhances overall response rates.
  3. Patient-Centric Approach: The manageable safety profile of Isa-VRd supports its use in a broader patient population, offering a promising treatment for those unable to undergo stem cell transplantation.

The IMROZ study presents compelling evidence supporting Isa-VRd as a superior treatment regimen for transplant-ineligible NDMM patients. By significantly improving progression-free survival and achieving higher rates of complete response and MRD negativity, this study underscores the transformative potential of incorporating isatuximab into standard treatment protocols. As we continue to advance in the era of personalized medicine, integrating novel therapies like Isa-VRd into clinical practice will be crucial for improving patient outcomes and quality of life in multiple myeloma. The insights from this study mark a significant step forward in the ongoing effort to optimize multiple myeloma treatment, offering new hope and improved survival prospects for patients facing this challenging disease.

References:

  1. Facon T, et al. J Clin Oncol 42, 2024 (suppl 16; abstr 7500)
  2. Clinical Benefit of SAR650984, Bortezomib, Lenalidomide and Dexamethasone Combination in NDMM Patients Not Eligible for Transplant (IMROZ)
Zachary Moore

Author Zachary Moore

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