Daratumumab for patients with myeloma with early or late relapse after initial therapy: Subgroup Analysis of CASTOR and POLLUX
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Daratumumab for patients with myeloma with early or late relapse after initial therapy: Subgroup Analysis of CASTOR and POLLUX. / Spencer, Andrew; Moreau, Philippe; Mateos, M V; Goldschmidt, Hartmut; Suzuki, Kenshi; Levin, Mark-David; Sonneveld, Pieter; Orlowski, Robert Z; Yoon, Sung-Soo; Usmani, Saad Z; Weisel, Katja C; Reece, Donna; Ahmadi, Tahamtan; Pei, Huiling; Garvin Mayo, Wendy; Gai, Xue; Carey, Jodi; Bartlett, J Blake; Carson, Robin; Dimopoulos, Meletios-Athanasios A.
in: BLOOD ADV, Jahrgang 8, Nr. 2, 23.01.2024, S. 388-398.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Daratumumab for patients with myeloma with early or late relapse after initial therapy: Subgroup Analysis of CASTOR and POLLUX
AU - Spencer, Andrew
AU - Moreau, Philippe
AU - Mateos, M V
AU - Goldschmidt, Hartmut
AU - Suzuki, Kenshi
AU - Levin, Mark-David
AU - Sonneveld, Pieter
AU - Orlowski, Robert Z
AU - Yoon, Sung-Soo
AU - Usmani, Saad Z
AU - Weisel, Katja C
AU - Reece, Donna
AU - Ahmadi, Tahamtan
AU - Pei, Huiling
AU - Garvin Mayo, Wendy
AU - Gai, Xue
AU - Carey, Jodi
AU - Bartlett, J Blake
AU - Carson, Robin
AU - Dimopoulos, Meletios-Athanasios A
N1 - Copyright © 2023 American Society of Hematology.
PY - 2024/1/23
Y1 - 2024/1/23
N2 - 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).
AB - 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).
U2 - 10.1182/bloodadvances.2023010579
DO - 10.1182/bloodadvances.2023010579
M3 - SCORING: Journal article
C2 - 38048391
VL - 8
SP - 388
EP - 398
JO - BLOOD ADV
JF - BLOOD ADV
SN - 2473-9529
IS - 2
ER -
