Time to response, duration of response, and patient-reported outcomes (PROs) with daratumumab (DARA) plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): Subgroup analysis of the phase 3 MAIA study.

person Thierry Facon University of Lille, CHU Lille, Service des Maladies du Sang, Lille, France info_outline Thierry Facon, Shaji Kumar, Torben Plesner, Philippe Moreau, Nizar J. Bahlis, Hartmut Goldschmidt, Michael O'Dwyer, Aurore Perrot, Christopher P. Venner, Katja Weisel, Joseph R. Mace, Noopur S. Raje, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Huiling Pei, Fredrik Borgsten, Saad Zafar Usmani

Authors person Thierry Facon University of Lille, CHU Lille, Service des Maladies du Sang, Lille, France info_outline Thierry Facon, Shaji Kumar, Torben Plesner, Philippe Moreau, Nizar J. Bahlis, Hartmut Goldschmidt, Michael O'Dwyer, Aurore Perrot, Christopher P. Venner, Katja Weisel, Joseph R. Mace, Noopur S. Raje, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Huiling Pei, Fredrik Borgsten, Saad Zafar Usmani Organizations University of Lille, CHU Lille, Service des Maladies du Sang, Lille, France, Department of Hematology, Mayo Clinic Rochester, Rochester, MN, Vejle Hospital and University of Southern Denmark, Vejle, Denmark, Hematology Department, University Hospital Hôtel-Dieu, Nantes, France, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada, University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg, Germany, Department of Medicine/Haematology, NUI, Galway, Ireland, CHU de Toulouse, IUCT-O, Université de Toulouse, UPS, Service d’Hématologie, Toulouse, France, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada, Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Florida Cancer Specialists, St. Petersburg, FL, Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA, CHD Vendée, La Roche Sur Yon, France, Centre Hospitalier Universitaire (CHU) de Caen, Caen, France, Department of Clinical Haematology, Hopital Necker-Enfants Malades, Paris, France, CHU Poitiers, Hôpital la Milétrie, Poitiers, France, Janssen Research & Development, LLC, Titusville, NJ, Janssen-Cilag, Birkerød, Denmark, Memorial Sloan Kettering Cancer Center, New York, NY Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: In the phase 3 MAIA study, adding DARA to Rd improved progression-free survival (primary endpoint), overall survival, duration of response, and PROs in transplant-ineligible pts with NDMM. We report a MAIA subgroup analysis of time to response, duration of response, and PROs. Methods: Transplant-ineligible pts with NDMM received 28-day cycles of Rd (R 25 mg PO on Days 1-21; d 40 mg PO QW) ± DARA (16 mg/kg IV QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter) until disease progression or unacceptable toxicity. Secondary endpoints included time to response and duration of response. PROs were measured using the EORTC QLQ-C30, with treatment effects assessed via mixed-effects model with repeated measures. Results: In total, 368 pts were assigned to the D-Rd group and 369 pts to the Rd group; 162 (44%) D-Rd pts and 142 (38%) Rd pts had renal impairment (defined as baseline CrCl ≤60 mL/min). At a 56.2-mo median follow-up, median times to very good partial response or better (≥VGPR) and complete response or better (≥CR) were shorter with D-Rd vs Rd in the overall study population and in the subgroups of pts with and without renal impairment (Table). Among pts who achieved ≥CR or partial response or better (≥PR), higher proportions of D-Rd vs Rd pts had not experienced disease progression at 48 mo (Table). Among pts with renal impairment, greater improvements from baseline in pt-reported pain, fatigue, and nausea and vomiting symptom scores were observed with D-Rd vs Rd across most timepoints; a notably greater meaningful reduction in pain symptom score was seen with D-Rd vs Rd as early as Cycle 6 Day 1 (least squares mean change from baseline, −14.9 vs −7.0; P =0.0241). Analyses for additional pt subgroups will be presented. Conclusions: In transplant-ineligible pts with NDMM, D-Rd showed more rapid deep responses as well as more durable responses vs Rd, regardless of renal function. Improvements in pt-reported symptoms were generally greater with D-Rd vs Rd in pts with renal impairment. Our results support the use of D-Rd in transplant-ineligible pts with NDMM. Clinical trial information: NCT02252172. All Responders (≥PR) Responders with Baseline CrCl >60 mL/min Responders with Baseline CrCl ≤60 mL/min D-Rd Rd D-Rd Rd D-Rd Rd Time to response Median (range), mo ≥CR 10.7 (1.0-46.7) 13.2 (2.8-54.6) 11.0 (1.0-41.9) 13.0 (2.8-47.9) 10.4 (3.0-46.7) 13.6 (5.6-54.6) ≥VGPR 3.0 (0.9-55.1) 4.7 (0.9-43.3) 3.0 (0.9-28.9) 4.7 (0.9-43.3) 2.9 (0.9-55.1) 4.9 (1.0-41.7) Duration of response Estimated 48-mo event-free rate, % (95% CI) ≥CR 81.8 (74.3-87.2) 57.8 (43.4-69.7) 82.2 (72.9-88.5) 55.3 (37.4-70.0) 81.0 (66.5-89.7) 61.5 (34.8-79.9) ≥PR 68.7 (63.1-73.5) 47.2 (40.8-53.3) 69.8 (62.4-76.0) 48.9 (40.8-56.5) 67.2 (58.5-74.5) 44.4 (34.1-54.3)