Dp121 | Pomalidomide, Bortezomib and Dexamethasone in Multiple Myeloma Patients Refractory to Lenalidomide and Anti-cd38 Monoclonal Antibodies: Real World Short-lived Responses Driven by Double Refractoriness
Year: 2025
Type: article
Abstract: Background: Drug refractoriness adversely impacts outcomes in relapsed/refractory multiple myeloma (MM) patients (pts). Increased frontline use of lenalidomide (Len) and anti-CD38 monoclonal antibodies (MoAbs) led to a growing number of pts double refractory (DR) after 1 or 2 lines of therapy (LoT). In this setting, on-label options remain limited. The PVD (pomalidomide, bortezomib, dexamethasone) regimen is approved, although pivotal OPTIMISMM trial excluded MoAb+Len DR pts, and real-world data are scarce. Aims: 1) outcomes of PVD in MoAb+Len DR MM pts after 1–2 LoT, 2) the prognostic role of time to double refractoriness (DRef) emergence. Methods: We retrospectively analyzed 77 MM pts DR to MoAbs+Len after 1–2 LoT, treated with PVD across 20 Italian centers (2020–2022). Ethics approval and informed consent were obtained. Variables were reported as counts (%) or medians (IQR). Progression-Free Survival (PFS) and Overall Survival (OS) were estimated via Kaplan-Meier method. PFS predictors were assessed with Cox model. Analyses were conducted using Stata 18. Results: Table 1 summarizes patient clinical features. Cytogenetic data were available for 45 pts (58%): 68.9% had high-risk features. Ten pts (13%) had extramedullary disease. 73% were DR after 1 LoT, mainly following frontline MoAbs+Len therapy. Median time from diagnosis to PVD initiation was 21.4 months (IQR: 11.5–34). Median PVD duration was 5.7 months (7 cycles). Median time to best response was 3 months (IQR: 1.9–4.5). Overall response rate was 75.8% (CR 18.6%, VGPR 28.6%, PR 28.6%). Median PFS was 9.4 months. Time to DRef, evaluated with 12, 18, and 24-month cut-offs, did not significantly impact PFS: median PFS was 9.8 vs 9.0 months for <12 vs ≥12 months (P=0.885); 8.2 vs 9.2 months for <18 vs ≥18 months (P=0.919); and 8.6 vs 9.2 months for <24 vs ≥24 months (P=0.695). OS was similarly unaffected: 18.1 vs 22.6 months for <24 vs ≥24 (P=0.901); 19.3 vs 22.6 for <18 vs ≥18 (P=0.905); 18.1 vs 22.6 for <12 vs ≥12 (P=0.351). In the 3-month landmark analysis, achieving ≥VGPR was not associated with improved PFS (HR=1.1; 95% CI: 0.6–2.1; P=0.753). Toxicity was consistent with the pivotal trial. Conclusions: In this real-world study, PVD showed activity in MoAb+Len DR MM after 1–2 LoT, though responses were short-lived. Timing to DRef onset did not impact outcomes, identifying DRef as a poor prognostic factor regardless of when it emerges with urgent need for novel options in this setting.
Authors: C. Liberatore, P. Tacchetti, C. Conticello, G. Barilà, E. Antonioli, A. Belotti, A.M. Cafro, L. Paris, V. Bongarzoni, M. Gentile, M. Da Vià, M. Quaresima, S. Pezzatti, F. Ciambelli, M. Garzia, O. Annibali, F. Fazio, G. Antolino, N. Sgherza, F. Farina, A. Citro, M. Galli, V. Del Fabro, C.S. Cartia, F. Fioritoni, K Mancuso, I. Attucci, M.L. Pioltelli, M. Puppi, S. Terlizzi, C. Lisi, M. Palumbo, V.V. Ferretti, S. Morè, M.T. Petrucci, S. Mangiacavalli
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093121504
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