Observational studyClinical and experimental medicine2025
A multicenter observational retrospective study of second-line treatment with daratumumab-bortezomib-dexamethasone (DaraVd) in multiple myeloma patients refractory to lenalidomide.
Observational study in Clinical and experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Article
- Efficacy and Safety of Isatuximab, Carfilzomib, and Dexamethasone (IsaKd) in Multiple Myeloma Patients at the First Relapse After Autologous Stem Cell Transplantation and Lenalidomide Maintenance: Results from the Multicenter, Real-Life AENEID Study.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Forcing Ahead: Second-Line Treatment Options for Lenalidomide-Refractory Multiple Myeloma.Cancers · 2025Review
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Authors and funding
26 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upfront lenalidomide in newly diagnosed multiple myeloma has become the gold standard. Nonetheless, proper management of lenalidomide-refractory patients is challenging. Daratumumab-bortezomib-dexamethasone (DaraVd) has been approved after ≥ 1 prior therapy, but data on upfront lenalidomide refractoriness are scarce. We run a retrospective study to assess the outcomes of 85 lenalidomide-refractory patients treated at first relapse with DaraVd in 10 Italian centers. Baseline characteristics were representative of a general population, despite inferior median age (57 years). Sixteen (27%) at diagnosis and 7 (29%) at relapse had high-risk cytogenetics (t(4;14) and/or t(14;16) and/or del17). Furthermore, one had del1p, one gain1q (3 copies) and one amp1q (≥ 4 copies) at diagnosis; one gain1q and one amp1q at relapse. Overall response rate was 86% (61% ≥ VGPR). Median PFS and OS were 15 and 47 months, respectively (25-months median follow-up). Previous dose/duration of lenalidomide did not influence PFS, favorably affected by the absence of amp1q (p = 0.04), bone marrow plasma cells < 60% (p = 0.003), absence of extramedullary-disease (p = 0.009), and ≥ VGPR (p < 0.001) or ≥ CR (p = 0.012). In a multivariate model, response ≥ VGPR was confirmed to be independently associated to PFS (median: 26 vs. 7 months). At least one grade ≥ 2 adverse event (AE) occurred in 67 (85%) patients. Most common AEs were hematological (72%), infections (30%, 8% grade-3, 1% grade-5), pneumonia (14%), and asthenia (38%). Peripheral neuropathy rate was 58% (8% grade-3). Toxicity-related bortezomib dose reduction occurred in 39 (49.4%) patients; 27 (44%) delayed Dara (1 median dose), mostly for infections. Three patients discontinued for toxicity. Collectively, second-line DaraVd remains an alternative in lenalidomide-refractory patients, especially for those ineligible for pomalidomide/carfilzomib-based regimens, T-cell-redirecting therapies or other experimental drugs.
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