P934: Daratumumab + Lenalidomide, Bortezomib, and Dexamethasone in Transplant-eligible Newly Diagnosed Multiple Myeloma: a Post Hoc Analysis of Sustained Minimal Residual Disease Negativity From Griffin
Year: 2022
Type: article
Abstract: Background: In the primary analysis of the phase 2 randomized GRIFFIN study, Daratumumab (DARA) + lenalidomide, bortezomib, and dexamethasone (D-RVd) improved the stringent complete response (sCR) rate by end of consolidation for transplant-eligible newly diagnosed multiple myeloma (NDMM) (42.4% vs 32.0%; 1-sided P = 0.068). With longer follow-up (median, 38.6 mo), D-RVd vs RVd improved minimal residual disease (MRD)-negativity (10–5) rates in clinically relevant subgroups (ISS stage III, 71% vs 36%; high cytogenetic risk, 44% vs 29% [del17p, t(4;14), or t(14;16)]; revised high cytogenetic risk, 55% vs 32% [del17p, t(4;14), t(14;16), t(14;20), or gain 1q]). Aims: In this post-hoc analysis we present results of sustained MRD negativity (median follow-up, 38.6 mo) in the same subgroups and in patients (pts) with ≥CR. Methods: Transplant-eligible NDMM pts were randomized 1:1 to 4 D-RVd/RVd induction cycles, ASCT, 2 D-RVd/RVd consolidation cycles, and 2 years of maintenance therapy with lenalidomide (R) ± DARA. For induction/consolidation (21-day cycles), pts received R (25 mg PO Days [D] 1-14), V (1.3 mg/m2 SC D1, 4, 8, 11), and d (40 mg PO weekly) ± DARA (16 mg/kg IV D1, 8, 15 of Cycles 1-4 and D1 of Cycles 5-6). In maintenance (28-day cycles), pts received R (10 mg PO D1-21; if tolerated, 15 mg in Cycles 10+) ± DARA (16 mg/kg IV Q8W/Q4W or 1800 mg SC per protocol amendments). The primary endpoint was sCR rate by end of consolidation. Results: The following features were balanced among randomized pts (D-RVd, n = 104; RVd, n = 103): high cytogenetic risk (16; 14), revised high cytogenetic risk (42; 37), gain 1q (34; 28), and ISS stage III (14; 14). Sustained MRD-negativity rates at 10–5 lasting ≥6 and ≥12 months were higher for D-RVd vs RVd among all high-risk subgroups (Table). D-RVd was superior to RVd for rates of sustained MRD negativity lasting ≥12 months for pts with ≥CR (53.7% vs 20.3%) and sCR (59.1% vs 17.4%; Table). Among all pts with sustained MRD negativity, only 1 D-RVd pt subsequently had disease progression, and 1 RVd pt died. Additional data on MRD at 10–6 and PFS will be presented. Image:Summary/Conclusion: MRD data in GRIFFIN show that the addition of DARA to RVd induction/consolidation and R maintenance may lead to durable MRD-negativity (10–5) rates in pts with transplant-eligible NDMM with high cytogenetic risk, ISS stage III, and those who achieve ≥CR or sCR, however larger studies are needed.
Source: HemaSphere
Authors: C. Rodriguez, J. L. Kaufman, J. Laubach, D. W. Sborov, B. Reeves, A. Chari, R. Silbermann, L. J. Costa, L. D. Anderson, N. Nathwani, N. Shah, N. Bumma, A. Jakubowiak, R. Z. Orlowski, H. Pei, A. Cortoos, S. Patel, T. S. Lin, P. G. Richardson, P. M. Voorhees
Institutions: Wake Forest University Health Sciences, Wake Forest University, Emory University, Winship Cancer Institute, Dana-Farber Cancer Institute, University of Utah, Huntsman Cancer Institute, University of North Carolina at Chapel Hill, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Oregon Health & Science University, OHSU Knight Cancer Institute, University of Alabama at Birmingham, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, City Of Hope National Medical Center, City of Hope, University of California, San Francisco, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, University of Chicago Medical Center, The University of Texas MD Anderson Cancer Center, Janssen Scientific Affairs (United States), Levine Cancer Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,480
OpenAlex ID: W4283388784