Daratumumab-Based Second Line Therapy Improves Outcomes After VRD Induction, Upfront Autologous Transplant, and...

For eligible patients with newly diagnosed multiple myeloma (MM), induction with VRD used to be the standard of care, followed by autologous stem cell transplantation (autoHCT) and lenalidomide maintenance. Most patients relapse and require second-line (2L) therapy.

We conducted a retrospective, single-center study of MM patients who received VRD induction, autoHCT between 2005-2021, and lenalidomide maintenance before relapse.

A total number of 146 patients were included, with a median age of 60 years (range, 32-80), and 39 (27%) patients had high-risk cytogenetics. Following first progression, 31%received an immunomodulatory drug (IMiD) + proteasome inhibitor (PI)-containing triplet as 2L therapy, 21% received an IMiD/PI-containing doublet, and 24% received a daratumumab (Dara)-based 2L therapy. Patients receiving Dara-based regimens had higher rates of ≥VGPR (63%) compared to those receiving other regimens (IMiD + PI triplet: 35%, IMiD/PI doublet: 34%) (P = .026). After a median follow-up of 35.8 months from 2L therapy, median PFS2 with Dara-based regimens was 59.9 months, versus 12.3 months and 11.5 months for doublets and triplets, respectively (P = .007). Median overall survival (OS) for the entire cohort was 52.6 months. In multivariable analysis, Dara-based therapy was associated with improved PFS2 (HR 0.35, P < .001), while clinical progression (vs. biochemical) predicted worse PFS2 (HR 1.58, P = .026). Progression ≥ 12 months post-autoHCT was associated with improved OS (HR 0.23, P < .001); busulfan-melphalan conditioning (HR 4.06, P < .001) and clinical progression (HR 1.99, P = .006) were associated with inferior OS.

Dara-based 2L regimens were associated with superior PFS2 approaching almost 5 years.