In anti-CD38 naïve patients with newly diagnosed multiple myeloma (NDMM) and measurable residual disease (MRD) after front-line autologous hematopoietic cell transplant (AHCT), adding the anti-CD38 antibody daratumumab to lenalidomide (D-R) as maintenance therapy showed benefits over lenalidomide (R) alone across all subgroups regardless of age, race, International Staging System (ISS) disease stage, or cytogenetics. This is according to a post hoc analysis of these clinically relevant subgroups in the phase III AURIGA trial. The results of this analysis were presented at the 66th American Society of Hematology Annual Meeting and Exposition.
“MRD-negative conversion at 12 months was better with D-R and deepened with longer maintenance,” said Laahn Foster, MD, of the University of Virginia in Charlottesville, who presented the results. “With longer follow-up, we are starting to see the long-term benefits translating into a progression-free survival (PFS) advantage across all these subgroups.”
The randomized study compared daratumumab-based to standard lenalidomide maintenance therapy in patients with NDMM who were anti-CD38 naïve and MRD positive after AHCT. Patients received 28-day cycles of R maintenance with or without subcutaneous daratumumab for up to 36 cycles or until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was the MRD-negative (10–5) conversion rate by 12 months from maintenance therapy initiation. The post hoc analysis included 200 patients, randomly assigned 1:1 to D-R or R. The clinically relevant subgroups, which had similar numbers per arm, were: age (<65 years, ≥65 years); race (Black, white); ISS stage I-III disease; response upon study entry (<CR, ≥CR), and high-risk cytogenetics at diagnosis per the standard definition (del[17p], t[4;14], t[14;16]) and the revised definition (also including t[14;20] and gain/amp[1q21]). The researchers also looked at high-risk disease per the International Myeloma Society (IMS) 2024 criteria. Because not all data were available, they used a modified version (≥ 20% del[17p], t[4;14], t[14;16], t[14;20] plus gain/amp[1q21] and/or del [1p32], and/or del [1p32] plus gain/amp[1q21]).
Compared with R, D-R maintenance improved the MRD-negative conversion rate by 12 months, regardless of age, race, ISS disease stage, or disease response upon study entry. A similar finding occurred among patient subgroups with standard-risk disease and ultra-high-risk disease, per the standard and modified criteria, and those with modified IMS 2024 high-risk disease.
“It’s not surprising that the MRD-negative conversion rate improved with the addition of daratumumab to lenalidomide. I was more surprised that the MRD-negative conversion was not higher with R alone,” Dr. Foster said. “With the abundance of data demonstrating the benefits of achieving MRD negativity, this study highlights the significant potential and opportunity to convert more patients to MRD-negative state with D-R post-transplant maintenance across all subgroups and keeping our patients in that deep response.”
At 32.3 months of median follow-up, the PFS hazard ratio point estimates among all subgroups favored D-R over R, including in those with various definitions of high cytogenetic risk and standard-risk disease. D-R maintenance led to PFS benefits over R regardless of the number of high-risk cytogenetic abnormalities (HRCAs). A similar finding occurred among patients with gain/amp(1q21), irrespective of other HRCAs.
The incidence of grade 3 or 4 treatment-emergent adverse events (TEAEs) stood higher for D-R than R for Black (75.0% vs. 66.7%) and white (76.6% vs 70.8%) patients, and those younger than 65 years (76.3% vs. 63.8%) but were similar in patients 65 years or older (70.3% vs. 72.5%). Compared with younger patients, no difference occurred in grade 3 or 4 infection rates or cytopenia among patients 65 years or older. D-R did not lead to additional safety concerns in the population of Black patients.
“Monotherapy R has been well established as the standard of care for post-transplant maintenance for a long time. Myeloma is a chronic disease, and achieving an optimal response while maintaining quality of life is a fine balance,” Dr. Foster said. “AURIGA and this subgroup analysis nicely demonstrated a clear benefit of the doublet D-R over R alone across all subgroups and with a very manageable toxicity profile.”
“The overall MRD-conversion rates increased and suggest deepening responses to D-R even after one year of maintenance. It remains to be determined the optimal duration for D-R. Is it one year of sustained MRD negativity, or is it longer?” Dr. Foster continued.
She concluded, “These results support using D-R maintenance post-transplant (rather than R alone) for at least a number of years with the goal of achieving sustained MRD negativity before deescalating maintenance to R alone.”
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Foster L, Anderson LD, Chung A, et al. Daratumumab plus lenalidomide (D-R) versus lenalidomide (R) alone as maintenance therapy in newly diagnosed multiple myeloma (NDMM) after transplant: analysis of the phase 3 Auriga study among clinically relevant subgroups. Abstract 675. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 8, 2024; San Diego, California.
