Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX.

Autor:	Spencer A; Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, Australia., Moreau P; Hematology Department, University Hospital Hôtel-Dieu, Nantes, France., Mateos MV; University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain., Goldschmidt H; University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases, Heidelberg, Germany., Suzuki K; Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan., Levin MD; Albert Schweitzer Hospital, Dordrecht, The Netherlands., Sonneveld P; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Orlowski RZ; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX., Yoon SS; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea., Usmani SZ; Memorial Sloan Kettering Cancer Center, New York, NY., Weisel K; Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Reece D; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada., Ahmadi T; Genmab US, Inc, Plainsboro, NJ., Pei H; Janssen Research & Development, LLC, Titusville, NJ., Mayo WG; Janssen Research & Development, LLC, Raritan, NJ., Gai X; Janssen Research & Development, LLC, Beijing, China., Carey J; Janssen Research & Development, LLC, Spring House, PA., Bartlett JB; Janssen Research & Development, LLC, Raritan, NJ., Carson R; Janssen Research & Development, LLC, Spring House, PA., Dimopoulos MA; National and Kapodistrian University of Athens, Athens, Greece.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Jan 23; Vol. 8 (2), pp. 388-398.
DOI:	10.1182/bloodadvances.2023010579
Abstrakt:	Abstract: High-risk multiple myeloma (MM) is often defined based on cytogenetic abnormalities, but patients who relapse early after initial therapy are considered a functional high-risk group. In the phase 3 CASTOR and POLLUX studies, daratumumab plus bortezomib/dexamethasone (D-Vd) or lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS), regardless of cytogenetic risk, and achieved higher rates of complete response or better (≥CR) and minimal residual disease (MRD) negativity vs that with Vd/Rd alone in relapsed/refractory MM. Post hoc analyses of CASTOR and POLLUX evaluated patient subgroups with 1 prior line of therapy based on timing of progression/relapse (early or late) after initiation of first line of therapy. PFS consistently favored the daratumumab-containing regimens across subgroups using both a 24- and 18-month early-relapse cutoff. In the CASTOR/POLLUX pooled data set, daratumumab reduced the risk of disease progression or death by 65% (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.26-0.48; P < .0001) in the early-relapse (<24 months) subgroup and by 65% (HR, 0.35; 95% CI, 0.26-0.47; P < .0001) in the late-relapse (≥24 months) subgroup. OS also favored the daratumumab-containing regimens in both the early-relapse (HR, 0.62; 95% CI, 0.45-0.86; P = .0036) and late-relapse (HR, 0.67; 95% CI, 0.48-0.93; P = .0183) subgroups in the pooled population using a 24-month cutoff. Rates of ≥CR and MRD negativity (10-5) were higher with daratumumab vs control, regardless of progression/relapse timing. Although daratumumab is unable to fully overcome the adverse prognosis of early relapse, our results support the use of daratumumab for patients with 1 prior line of therapy, including for those who progress/relapse early after initial therapy and are considered to have functional high-risk MM. These trials were registered at www.clinicaltrials.gov as #NCT02136134 (CASTOR) and #NCT02076009 (POLLUX). (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu