KRd-Based Quadruplets May “Eliminate” Transplant Need for Multiple Myeloma

Contextualized by his presentation of results from an analysis of a high-risk subset of patients from the phase 3 ATLAS trial (NCT02659293) evaluating carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) following autologous stem cell transplantation in newly diagnosed multiple myeloma, Andrezj Jakubowiak, MD, PhD, discussed how he sequences treatment for these patients.¹

He began by asserting that KRd previously exhibited a 60% minimal residual disease (MRD) negativity rate in this patient population, which is a strategy his center prefers for this group. Additionally, he expressed that his center has utilized KRd-based regimens in the first-line setting, with data suggesting that its use in quadruplets may help to further bolster outcomes for patients.

Furthermore, Jakubowiak highlighted results from the phase 3 MIDAS trial (NCT04934475), which found that patients treated with isatuximab-irfc (Sarclisa) added to a KRd background experienced similar rates of MRD negativity vs autologous stem cell transplantation.² He concluded by suggesting that these findings may help reduce the need for transplantation, which carries of risk secondary malignancies.

Jakubowiak is a professor of Medicine and director of the Myeloma Program at the University of Chicago.

Transcript:

If patients [have] high-risk disease, in our center—and based on data—we prefer a treatment strategy that has the best chance of achieving MRD negativity in 10^-6, and KRd showed that with high success. We published previously that KRd followed by transplant and followed by KRd gives about 60% MRD negativity in 10^-6 for extended treatment. From my perspective, not having enough data from other strategies on how high-risk patients are affected by different treatment strategies post-transplant, I would prioritize KRd or a KRd combination, if that could be acceptable from the regulatory perspective.

Our choice for initial therapy in our center has been, for a long time, a KRd-based regimen. We have published data with daratumumab [Darzalex] plus KRd [dara-KRd] and with elotuzumab [Empliciti] plus KRd [elo-KRD]; they are outstanding. I would add to that an important comment: these are, to some extent, not high-level evidence as phase 3 [data], but they are showing quite good and convincing evidence why I am prioritizing KRd as initial therapy. In these quadruplet studies with daratumumab or elotuzumab, we already showed [most] patients achieve the deepest level of MRD negativity. What it means [is] that for these patients, there is a potential, as the MIDAS trial showed, to eliminate a need for transplant, which has toxicities…during the transplant, but also a long-term risk of second malignancy.

References

1. Jakubowiak A, Wrobel T, Jamroziak K, et al. Carfilzomib, lenalidomide, and dexamethasone (KRd) after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: analysis of high-risk subset in phase 3 ATLAS trial. Presented at: 22nd Annual International Myeloma Society (IMS) Meeting and Exposition; September 17-20, 2025, Toronto, Canada. Abstract OA-51.
2. Perrot A, Lambert J, Hulin C, et al. Measurable residual disease-guided therapy in newly diagnosed myeloma. N Engl J Med. Published online June 3, 2025. doi:10.1056/NEJMoa2505133