Richardson Paul G, O'Donnell Elisabeth K, O'Gorman Peter, Leypoldt Lisa B, Laubach Jacob, Gay Francesca, Leleu Xavier, Facon Thierry, Moreau Philippe, Dimopoulos Meletios A, Goldschmidt Hartmut, Mai Elias K, Cavo Michele, Weisel Katja C, Berdeja Jesus G, Orlowski Robert Z, Beksaç Meral, Perrot Aurore, Mikhael Joseph, Martin Thomas
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Haematology Department, The Mater Misericordiae University Hospital, Dublin, Ireland.
Expert Opin Investig Drugs. 2025 Jul-Aug;34(7-8):571-589. doi: 10.1080/13543784.2025.2532446. Epub 2025 Jul 23.
The addition of the anti-CD38 monoclonal antibody isatuximab to standard therapies is transforming the care of patients with newly diagnosed multiple myeloma (NDMM), as previously seen in the relapsed/refractory setting. This is particularly important for patients with NDMM as early treatment with effective, well tolerated therapies may ensure better clinical outcomes.
Here, we examine recent results from pivotal Phase 3 and 2 clinical trials that demonstrate efficacy and safety of isatuximab across multiple combinations, for both transplant-ineligible and transplant-eligible NDMM patients. We then evaluate long-term outcomes from the IKEMA and ICARIA-MM trials as well as real-world evidence emerging from analyses conducted in patients with relapsed/refractory MM (RRMM). Further, we address current approaches to optimize treatment with isatuximab-based combinations involving changes in bortezomib or dexamethasone dosing. Lastly, we review current findings with new administration modalities developed to optimize delivery of isatuximab in the clinic.
Supported by multiple lines of high-level evidence, isatuximab in combination with standard-of-care backbone therapies produces triplet or quadruplet regimens with enhanced efficacy and consistent safety for the treatment of patients with NDMM and RRMM.
将抗CD38单克隆抗体isatuximab添加到标准疗法中正在改变新诊断的多发性骨髓瘤（NDMM）患者的治疗方式，这与之前在复发/难治性环境中看到的情况相同。对于NDMM患者来说，这尤为重要，因为早期使用有效且耐受性良好的疗法进行治疗可能会确保更好的临床结果。
在此，我们研究了关键的3期和2期临床试验的最新结果，这些结果证明了isatuximab在多种联合方案中的疗效和安全性，适用于不符合移植条件和符合移植条件的NDMM患者。然后，我们评估了IKEMA和ICARIA-MM试验的长期结果，以及在复发/难治性多发性骨髓瘤（RRMM）患者中进行的分析得出的真实世界证据。此外，我们探讨了当前优化基于isatuximab联合治疗的方法，包括硼替佐米或地塞米松剂量的变化。最后，我们回顾了目前在临床中为优化isatuximab给药而开发的新给药方式的研究结果。
在多条高水平证据的支持下，isatuximab与标准治疗主干疗法联合使用，可产生三联或四联方案，在治疗NDMM和RRMM患者时具有更高的疗效和一致的安全性。
