P-369: OPTIMIZING THE ALCYONE TRIAL: EFFICACY OF DARATUMUMAB AND BORTEZOMIB MAINTENANCE IN NON-TRANSPLANT ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS POST DARA-VMP INDUCTION, 1 YEAR ANALYSIS

Introduction: Outcomes for non-transplant eligible newly diagnosed (ND) multiple myeloma (MM) patients have significantly improved with the inclusion of daratumumab (Dara) in the first line of therapy, as demonstrated by the ALCYONE clinical trial. However, its median TTP (39.3 months) was inferior to continuous Dara-Rd (MAIA trial: 62 months). A potential explanation for this disparity is that in ALCYONE patients only received Dara maintenance, whereas patients in the MAIA received Dara + lenalidomide. We aim to investigate whether extended treatment with bortezomib and Dara (Dara-V) may improve survival in these patients.

Methods: This multicenter, prospective, observational study enrolled patients who planned to receive Dara-V maintenance per usual clinical practice (Dara 1,800 mg SC every month and bortezomib 1.3 mg/m² SC every other week) until disease progression or unacceptable toxicity, following 9 cycles of Dara-VMP induction.

Results: In total 119 patients were recruited. Median age at diagnosis was 78.8 years (66.1 – 91). Among them, 31 (26.1%) had ISS stage III, 24 (20.2%) had extramedullary disease, and 34 (34%) had high-risk cytogenetics. ECOG performance status was assessed in 64 (53.8%) patients and only 3 (4.7%) had a score ≥ 3. Notably, 20 (16.8%) patients had an estimated glomerular filtration rate < 40, which was an exclusion criterion in ALCYONE.

After induction therapy, 74 (62.2%) patients had achieved a very good partial response (VGPR) or better. One year after the start of maintenance depth of response continued to improve, with 93 (78.2%) patients achieving VGPR or better.

In the ALCYONE, 292 patients were progression-free after induction and 207 after the first year of maintenance (approximately 85 [29.1%] progressions in that time). In our study six (5.0%) patients progressed during the same period and one (0.9%) died due to causes unrelated to progression or toxicity. Consequently, PFS and OS rates were 94.1% and 99.2%, respectively.

Regarding safety, 55 (46.2%) patients experienced adverse events (AE), and 14 (11.8%) serious adverse events (SAE). In total 152 AEs and only 19 (12.5%) SAEs. Of these, 13 (9.5%) AEs and 6 (31.6%) SAEs were grade ≥ 3. The most common AE was infections (40.1%), followed by gastrointestinal disorders (9.2%). Five (3.2%) events of peripheral neuropathy were reported. Nine (7.6%) patients experienced hematological toxicity, 5 (55.6%) being grade ≥ 3. One (0.8%) patient discontinued bortezomib; none daratumumab, and 5 (4.2%) required bortezomib dose reduction.

Conclusions: In real life, the addition of bortezomib to single-agent Daratumumab as maintenance after induction with Dara-VMP in non-transplant eligible NDMM patients seems to improve outcomes, with only 5% of patients relapsing/progressing in the first year. This may be superior compared to data from Alcyone. Long-term follow-up is required to confirm these findings, but this approach could be an alternative for patients intolerant to lenalidomide.