Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX
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/dexamethas...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 23 2024
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| In: |
Blood advances
Year: 2024, Volume: 8, Issue: 2, Pages: 388-398 |
| ISSN: | 2473-9537 |
| DOI: | 10.1182/bloodadvances.2023010579 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/bloodadvances.2023010579
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| Author Notes: | Andrew Spencer, Philippe Moreau, Maria-Victoria Mateos, Hartmut Goldschmidt, Kenshi Suzuki, Mark-David Levin, Pieter Sonneveld, Robert Z. Orlowski, Sung-Soo Yoon, Saad Z. Usmani, Katja Weisel, Donna Reece, Tahamtan Ahmadi, Huiling Pei, Wendy Garvin Mayo, Xue Gai, Jodi Carey, J. Blake Bartlett, Robin Carson, and Meletios A. Dimopoulos |
| Summary: | 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). |
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| Item Description: | Vorab veröffentlicht: 4. Dezember 2023 Gesehen am 12.11.2024 |
| Physical Description: | Online Resource |
| ISSN: | 2473-9537 |
| DOI: | 10.1182/bloodadvances.2023010579 |