Scientific publications

Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE. Scientific Publication

Nov 1, 2021 | Magazine: Clinical Lymphoma, Myeloma & Leukemia

Maria-Victoria Mateos  1 , Meletios A Dimopoulos  2 , Michele Cavo  3 , Kenshi Suzuki  4 , Stefan Knop  5 , Chantal Doyen  6 , Paulo Lucio  7 , Zsolt Nagy  8 , Ludek Pour  9 , Sebastian Grosicki  10 , Andre Crepaldi  11 , Anna Marina Liberati  12 , Philip Campbell  13 , Sung-Soo Yoon  14 , Genadi Iosava  15 , Tomoaki Fujisaki  16 , Mamta Garg  17 , Shinsuke Iida  18 , Joan Bladé  19 , Jon Ukropec  20 , Huiling Pei  21 , Rian Van Rampelbergh  22 , Anupa Kudva  23 , Ming Qi  24 , Jesus San-Miguel  25


Background: In the phase 3 ALCYONE study, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) significantly improved progression-free survival (PFS) and overall survival (OS) in transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. We present a subgroup analysis of ALCYONE by patient frailty status.

Patients and methods: Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit (0), intermediate (1), or frail (≥2); a nonfrail category combined fit and intermediate patients.

Results: Among randomized patients (D-VMP, n = 350; VMP, n = 356), 391 (55.4%) were nonfrail (D-VMP, 187 [53.4%]; VMP, 204 [57.3%]) and 315 (44.6%) were frail (163 [46.6%]; 152 [42.7%]). After 40.1-months median follow-up, nonfrail patients had longer PFS and OS than frail patients, but benefits of D-VMP versus VMP were maintained across subgroups: PFS nonfrail (median, 45.7 vs. 19.1 months; hazard ratio [HR], 0.36; P < .0001), frail (32.9 vs. 19.5 months; HR, 0.51; P < .0001); OS nonfrail (36-month rate, 83.6% vs. 74.5%), frail (71.4% vs. 59.0%).

Improved greater than or equal to complete response and minimal residual disease (10-5)-negativity rates were observed for D-VMP versus VMP across subgroups. The 2 most common grade 3/4 treatment-emergent adverse events were neutropenia (nonfrail: 39.2% [D-VMP] and 42.4% [VMP]; frail: 41.3% and 34.4%) and thrombocytopenia (nonfrail: 32.8% and 36.9%; frail: 36.9% and 39.1%).

Conclusion: Our findings support the clinical benefit of D-VMP in transplant-ineligible NDMM patients enrolled in ALCYONE, regardless of frailty status.

Trial registration: ClinicalTrials.gov NCT02195479.

CITATION Clin Lymphoma Myeloma Leuk. 2021 Nov;21(11):785-798. doi: 10.1016/j.clml.2021.06.005. Epub 2021 Jun 18.