Updates to NCCN Guidelines for Multiple Myeloma: Recently Approved First-Line Treatments for Patients With NDMM Eligible and Ineligible for Transplant

The NCCN guidelines for multiple myeloma were updated on September 17, 2024, to include isatuximab plus bortezomib, lenalidomide, and dexamethasone as a first-line preferred regimen for patients who are not candidates for transplant, as well as those who are candidates for transplant.¹ In addition, daratumumab, lenalidomide, bortezomib, and dexamethasone (D-VRd) has been added as a first-line preferred regimen for patients who are eligible for transplant.¹

Following the updated NCCN guidelines and based on the results of the IMROZ phase 3 study, isatuximab, in combination with VRd, was approved on September 20, 2024, by the FDA as a first-line treatment option for adults with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem-cell transplant (ASCT).¹ Isatuximab represents the first anti-CD38 therapy that, when combined with the standard treatment regimen of VRd, has been shown to significantly decrease the risk of disease progression or mortality by 40% in patients with NDMM who are not candidates for transplantation compared with VRd alone. The safety and tolerability of isatuximab demonstrated in the IMROZ study aligned with the known safety profile of isatuximab and VRd, with no new safety signals identified.¹

Prior to the updated guidelines, in July 2024, the FDA approved subcutaneous D-VRd for induction and consolidation in patients with NDMM who are candidates for ASCT based on favorable efficacy and safety data from the PERSEUS trial.³

In addition, the Supplemental Biologics License Application submitted to the FDA in September 2024 for the approval of D-VRd for the treatment of adult patients with NDMM for whom ASCT is deferred or those who are ineligible for ASCT, supported by data from the phase 3 CEPHEUS trial, showed that patients treated with D-VRd experienced a minimal residual disease–negativity rate (10⁻⁵ sensitivity) of 60.9% compared with 39.4% for patients treated with VRd alone.⁴

The inclusion of isatuximab or daratumumab in combination with VRd for patients with transplant-ineligible and -eligible NDMM are important breakthroughs for their care.

References

1. NCCN. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Multiple Myeloma. Version 1.2025. September 17, 2024. Accessed November 12, 2024. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1445
2. Sanofi [press release]. Sarclisa approved in the US as the first anti-CD38 therapy in combination with standard-of-care treatment for adult patients with newly diagnosed multiple myeloma not eligible for transplant. September 21, 2024. Accessed November 12, 2024. https://www.sanofi.com/en/media-room/press-releases/2024/2024-09-20-22-36-34-2949916
3. Rosa K. FDA approves subcutaneous daratumumab plus VRd in multiple myeloma. July 30, 2024. Accessed November 12, 2024. https://www.onclive.com/view/fda-approves-subcutaneous-daratumumab-plus-vrd-in-multiple-myeloma
4. Doherty K. sBLA submitted to FDA for subcutaneous daratumumab plus VRd in transplant-eligible multiple myeloma. January 21, 2024. Accessed November 12, 2024. https://www.onclive.com/view/sbla-submitted-to-fda-for-subcutaneous-daratumumab-plus-vrd-in-transplant-eligible-multiple-myeloma