(PA-427) Optimizing the Alcyone Trial: Efficacy of Daratumumab and Bortezomib Maintenance in Transplant-ineligible Newly Diagnosed Multiple Myeloma Patients Post DVMP Induction, 2 Year Analysis

Daratumumab (D) has represented a paradigm shift in the treatment of transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM), as shown in the ALCYONE and MAIA trials. Although no head-to-head comparison between daratumumab, bortezomib, melphalan and prednisone (DVMP) and daratumumab, lenalidomide and dexamethasone (DRd) exists, both achieved comparable rates of minimal residual disease (MRD) negativity. However, median progression-free survival (PFS) with DVMP is shorter than DRd (≈3 vs. ≈5 years), possibly due to differences in maintenance strategies: D monotherapy in ALCYONE vs. continuous DRd in MAIA. In this context, the Spanish Myeloma Group investigated whether continuous double maintenance with D and bortezomib (DV) after DVMP induction could improve outcomes. Here, we present the updated results after 2 years of DV maintenance.

Methods:

In this prospective, multicenter observational study, TIE NDMM patients received DV maintenance (D 1800 mg SC monthly + bortezomib 1.3 mg/m² SC biweekly) after 9 cycles of Dara-VMP, until progression or unacceptable toxicity. The data cut-off was April 30, 2025.

Results:

A total of 118 patients were enrolled (Nov 2021 - May 2023). Median age was 77 years (range, 65 – 90), 78% were ≥75 years. Twenty-six percent had an International Staging System (ISS) 3 and 34% high-risk cytogenetics. Notably, 33 patients (27.9%) would have been excluded from the ALCYONE trial, mainly due to an estimated glomerular filtration rate < 40 ml/min (27/33, 81.8%).

The rate of a very good partial response or better after induction was 62%, increasing to 78% after 1 year of maintenance and 81% after 2 years. In the MRD-evaluable population (n=53), 45% achieved MRD negativity.

After a median follow-up of 32 months (range, 7-55), the 2-year PFS and overall survival (OS) were 73% and 90%. No significant differences in response or survival were seen by ISS or cytogenetics risk. Comparative data with the ALCYONE trial will be presented at the meeting.

During maintenance, 87 (74%) patients experienced adverse events (AE), and 32 (27%) serious adverse events (SAE). A total of 304 AEs and 51 SAEs were reported. Infections, especially respiratory tract, were the most common (AEs: n=117, 39%; and SAE: n=23, 45%). Hematologic, cardiac or neurologic toxicity and secondary malignancies were uncommon (< 5%). Only 3 patients were discontinued due to toxicity (1 DV; 2 V), with no toxicity-related deaths.

Conclusions:

After 2 years of DV maintenance following DVMP in TIE NDMM patients showed sustained efficacy with manageable safety profile, even in an older and challenging population. While longer follow-up is needed, this strategy may represent a valuable option for patients who are ineligible for quadruplet therapies and/or intolerant to lenalidomide.