Maria-Victoria Mateos1, Meletios A Dimopoulos2, Michele Cavo3, Kenshi Suzuki4, Stefan Knop5, Chantal Doyen6, Paulo Lucio7, Zsolt Nagy8, Ludek Pour9, Sebastian Grosicki10, Andre Crepaldi11, Anna Marina Liberati12, Philip Campbell13, Sung-Soo Yoon14, Genadi Iosava15, Tomoaki Fujisaki16, Mamta Garg17, Shinsuke Iida18, Joan Bladé19, Jon Ukropec20, Huiling Pei21, Rian Van Rampelbergh22, Anupa Kudva23, Ming Qi24, Jesus San-Miguel25. 1. University Hospital of Salamanca/IBSAL, Cancer Research Center IBMCC (USAL-CSIC), Salamanca, Spain. Electronic address: mvmateos@usal.es. 2. National and Kapodistrian University of Athens, Athens, Greece. 3. IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Istituto di Ematologia "Seràgnoli", Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi, Bologna, Italy. 4. Japanese Red Cross Medical Center, Department of Hematology, Tokyo, Japan. 5. Würzburg University Medical Center, Würzburg, Germany. 6. Université Catholique de Louvain, Yvoir, Belgium. 7. Champalimaud Centre for the Unknown, Lisbon, Portugal. 8. Semmelweis Egyetem, Budapest, Hungary. 9. University Hospital Brno, Brno-Bohunice-Brno-Starý Lískovec, Czech Republic. 10. Department of Hematology and Cancer Prevention in Chorzów, Faculty of Health Sciences in Bytom, Medical University of Silesia, Katowice, Poland. 11. Clinica de Tratamento E, Cuiaba, Brazil. 12. Università degli Studi di Perugia Azienda Ospedaliera "Santa Maria," Terni, Italy. 13. Andrew Love Cancer Centre, University Hospital Geelong, Geelong, VIC, Australia. 14. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. 15. Medinvest-Institute of Hematology, Tbilisi, Georgia. 16. Matsuyama Red Cross Hospital, Matsuyama, Japan. 17. Leicester Royal Infirmary - Haematology, Leicester, United Kingdom. 18. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku Nagoya, Japan. 19. Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. 20. Janssen Global Medical Affairs, Horsham, PA. 21. Janssen Research & Development, LLC, Titusville, NJ. 22. Janssen Research & Development, Beerse, Belgium. 23. Janssen Research & Development, LLC, Raritan, NJ. 24. Janssen Research & Development, LLC, Spring House, PA. 25. Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarra, Spain.
Abstract
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.
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.