OVERALL SURVIVAL RESULTS WITH DARATUMUMAB, LENALIDOMIDE, AND DEXAMETHASONE VERSUS LENALIDOMIDE AND DEXAMETHASONE IN TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PHASE 3 MAIA STUDY
Author(s): ,
Thierry Facon
Affiliations:
University of Lille, CHU Lille, Service des Maladies du Sang,Lille,France
,
Shaji K. Kumar
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester, MN,United States
,
Torben Plesner
Affiliations:
Vejle Hospital and University of Southern Denmark,Vejle,Denmark
,
Robert Z. Orlowski
Affiliations:
Department of Lymphoma and Myeloma,The University of Texas MD Anderson Cancer Center,Houston, TX,United States
,
Philippe Moreau
Affiliations:
Hematology,University Hospital Hôtel-Dieu,Nantes,France
,
Nizar Bahlis
Affiliations:
Arnie Charbonneau Cancer Research Institute, University of Calgary,Calgary, AB,Canada
,
Supratik Basu
Affiliations:
Royal Wolverhampton NHS Trust and University of Wolverhampton,Wolverhampton,United Kingdom
,
Hareth Nahi
Affiliations:
Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge,Stockholm,Sweden
,
Cyrille Hulin
Affiliations:
Department of Hematology,Hôpital Haut Lévêque, University Hospital,Pessac,France
,
Hang Quach
Affiliations:
University of Melbourne, St Vincent’s Hospital,Melbourne,Australia
,
Hartmut Goldschmidt
Affiliations:
University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT),Heidelberg,Germany
,
Michael O’Dwyer
Affiliations:
Department of Medicine/Haematology,NUI,Galway,Ireland
,
Aurore Perrot
Affiliations:
CHU de Toulouse, IUCT-O, Université de Toulouse, UPS, Service d’Hématologie,Toulouse,France
,
Christopher P. Venner
Affiliations:
Cross Cancer Institute, University of Alberta,Edmonton, AB,Canada
,
Katja Weisel
Affiliations:
Department of Oncology,Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf,Hamburg,Germany
,
Joseph R. Mace
Affiliations:
Florida Cancer Specialists,St. Petersburg, FL,United States
,
Noopur Raje
Affiliations:
Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center,Boston, MA,United States
,
Mourad Tiab
Affiliations:
CHD Vendée,La Roche sur Yon,France
,
Margaret Macro
Affiliations:
Centre Hospitalier Universitaire (CHU) de Caen,Caen,France
,
Laurent Frenzel
Affiliations:
Department of Clinical Haematology,Hopital Necker-Enfants Malades,Paris,France
,
Xavier Leleu
Affiliations:
CHU Poitiers, Hôpital la Milétrie,Poitiers,France
,
Tahamtan Ahmadi
Affiliations:
Genmab US, Inc.,Plainsboro, NJ,United States
,
Jianping Wang
Affiliations:
Janssen Research & Development, LLC,Raritan, NJ,United States
,
Rian Van Rampelbergh
Affiliations:
Janssen Research & Development,Beerse,Belgium
,
Clarissa M. Uhlar
Affiliations:
Janssen Research & Development, LLC,Spring House, PA,United States
,
Brenda Tromp
Affiliations:
Janssen Research & Development, LLC,Leiden,Netherlands
,
Maria Delioukina
Affiliations:
Janssen Research & Development, LLC,Spring House, PA,United States
,
Jessica Vermeulen
Affiliations:
Janssen Research & Development, LLC,Leiden,Netherlands
Saad Z. Usmani
Affiliations:
Levine Cancer Institute/Atrium Health,Charlotte, NC,United States
EHA Library. Facon T. 06/12/21; 330171; LB1901
Prof. Thierry Facon
Prof. Thierry Facon
Contributions
Abstract
This abstract is embargoed until Saturday, June 12, 09:00 CEST
Presentation during EHA2021: The Late-Breaking Oral Session will be held on Saturday, June 12, 2021 (16:00 - 17:30 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: LB1901

Type: Oral Presentation

Session title: Late-Breaking Oral Session

Background
The primary analyses of the phase 3 ALCYONE, MAIA, and CASSIOPEIA studies established the superior clinical efficacy of daratumumab (DARA) in combination with standard-of-care regimens versus standard of care alone for patients with newly diagnosed multiple myeloma (NDMM). In ALCYONE, after longer follow-up, an overall survival (OS) benefit was observed; adding DARA to bortezomib, melphalan, and prednisone significantly reduced the risk of death by 40%. In the primary analysis of MAIA, DARA plus lenalidomide and dexamethasone (D-Rd) reduced the risk of disease progression or death by 44% versus lenalidomide and dexamethasone (Rd).

Aims
To report the updated efficacy and safety of D-Rd versus Rd after almost 5 years of median follow-up in transplant-ineligible patients with NDMM from the prespecified interim OS analysis of MAIA (NCT02252172).

Methods
Patients with NDMM ineligible for high-dose chemotherapy and autologous stem cell transplantation due to age ≥65 years or comorbidities were randomized 1:1 to D-Rd or Rd. All patients received 28-day cycles of Rd (R: 25 mg orally once daily on Days 1‑21; d: 40 mg orally on Days 1, 8, 15 and 22) with or without DARA (16 mg/kg intravenously once weekly for Cycles 1‑2, once every 2 weeks for Cycles 3-6, and once every 4 weeks thereafter). In both arms, patients were treated until disease progression or unacceptable safety events. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall response rate (ORR), OS, and safety.

Results
737 patients (D-Rd, 368; Rd, 369) were enrolled in this study. Baseline characteristics were well balanced between arms. The median age was 73 (range, 45-90) years. After a median follow-up of almost 5 years (56.2 months), a significant 32% reduction in the risk of death was observed with D-Rd versus Rd; median OS was not reached (NR) in either arm (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.53-0.86; P=0.0013 [crossing the prespecified stopping boundary of P=0.0414]). The estimated 5-year OS rate was 66.3% with D-Rd and 53.1% with Rd (Figure A). The updated median PFS was NR with D-Rd versus 34.4 months with Rd (HR, 0.53; 95% CI, 0.43-0.66; P<0.0001; Figure B). The estimated 5-year PFS rate was 52.5% with D-Rd and 28.7% with Rd. The updated ORR was 92.9% with D-Rd versus 81.6% with Rd (P<0.0001). No new safety signals were identified with longer follow-up. The most common (in >15% of patients in either arm) grade 3/4 treatment-emergent adverse events for the D-Rd/Rd arms were neutropenia (54.1%/37.0%, respectively), pneumonia (19.2%/10.7%), anemia (16.8%/21.6%), and lymphopenia (16.5%/11.2%). 

Conclusion
After almost 5 years of follow-up, a significant and clinically meaningful OS improvement was demonstrated with the use of D-Rd versus Rd in patients with NDMM who are transplant ineligible, representing a 32% reduction in the risk of death. The significant PFS benefit of D-Rd versus Rd from the primary analysis (median follow-up, 28 months) was maintained, with a 47% reduction in risk of disease progression or death and a median PFS for D-Rd NR. The favorable benefit-risk profile observed supports the use of D-Rd in transplant-ineligible patients with NDMM. These results, together with the OS benefit observed in ALCYONE, support the use of frontline DARA-based combination regimens to maximize PFS for optimal long-term outcomes.

Keyword(s): Monoclonal antibody, Multiple myeloma, Survival

This abstract is embargoed until Saturday, June 12, 09:00 CEST
Presentation during EHA2021: The Late-Breaking Oral Session will be held on Saturday, June 12, 2021 (16:00 - 17:30 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: LB1901

Type: Oral Presentation

Session title: Late-Breaking Oral Session

Background
The primary analyses of the phase 3 ALCYONE, MAIA, and CASSIOPEIA studies established the superior clinical efficacy of daratumumab (DARA) in combination with standard-of-care regimens versus standard of care alone for patients with newly diagnosed multiple myeloma (NDMM). In ALCYONE, after longer follow-up, an overall survival (OS) benefit was observed; adding DARA to bortezomib, melphalan, and prednisone significantly reduced the risk of death by 40%. In the primary analysis of MAIA, DARA plus lenalidomide and dexamethasone (D-Rd) reduced the risk of disease progression or death by 44% versus lenalidomide and dexamethasone (Rd).

Aims
To report the updated efficacy and safety of D-Rd versus Rd after almost 5 years of median follow-up in transplant-ineligible patients with NDMM from the prespecified interim OS analysis of MAIA (NCT02252172).

Methods
Patients with NDMM ineligible for high-dose chemotherapy and autologous stem cell transplantation due to age ≥65 years or comorbidities were randomized 1:1 to D-Rd or Rd. All patients received 28-day cycles of Rd (R: 25 mg orally once daily on Days 1‑21; d: 40 mg orally on Days 1, 8, 15 and 22) with or without DARA (16 mg/kg intravenously once weekly for Cycles 1‑2, once every 2 weeks for Cycles 3-6, and once every 4 weeks thereafter). In both arms, patients were treated until disease progression or unacceptable safety events. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall response rate (ORR), OS, and safety.

Results
737 patients (D-Rd, 368; Rd, 369) were enrolled in this study. Baseline characteristics were well balanced between arms. The median age was 73 (range, 45-90) years. After a median follow-up of almost 5 years (56.2 months), a significant 32% reduction in the risk of death was observed with D-Rd versus Rd; median OS was not reached (NR) in either arm (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.53-0.86; P=0.0013 [crossing the prespecified stopping boundary of P=0.0414]). The estimated 5-year OS rate was 66.3% with D-Rd and 53.1% with Rd (Figure A). The updated median PFS was NR with D-Rd versus 34.4 months with Rd (HR, 0.53; 95% CI, 0.43-0.66; P<0.0001; Figure B). The estimated 5-year PFS rate was 52.5% with D-Rd and 28.7% with Rd. The updated ORR was 92.9% with D-Rd versus 81.6% with Rd (P<0.0001). No new safety signals were identified with longer follow-up. The most common (in >15% of patients in either arm) grade 3/4 treatment-emergent adverse events for the D-Rd/Rd arms were neutropenia (54.1%/37.0%, respectively), pneumonia (19.2%/10.7%), anemia (16.8%/21.6%), and lymphopenia (16.5%/11.2%). 

Conclusion
After almost 5 years of follow-up, a significant and clinically meaningful OS improvement was demonstrated with the use of D-Rd versus Rd in patients with NDMM who are transplant ineligible, representing a 32% reduction in the risk of death. The significant PFS benefit of D-Rd versus Rd from the primary analysis (median follow-up, 28 months) was maintained, with a 47% reduction in risk of disease progression or death and a median PFS for D-Rd NR. The favorable benefit-risk profile observed supports the use of D-Rd in transplant-ineligible patients with NDMM. These results, together with the OS benefit observed in ALCYONE, support the use of frontline DARA-based combination regimens to maximize PFS for optimal long-term outcomes.

Keyword(s): Monoclonal antibody, Multiple myeloma, Survival

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