TY - JOUR
T1 - Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma
T2 - The GRIFFIN trial
AU - Voorhees, Peter M.
AU - Kaufman, Jonathan L.
AU - Laubach, Jacob
AU - Sborov, Douglas W.
AU - Reeves, Brandi
AU - Rodriguez, Cesar
AU - Chari, Ajai
AU - Silbermann, Rebecca
AU - Costa, Luciano J.
AU - Anderson, Larry D.
AU - Nathwani, Nitya
AU - Shah, Nina
AU - Efebera, Yvonne A.
AU - Holstein, Sarah A.
AU - Costello, Caitlin
AU - Jakubowiak, Andrzej
AU - Wildes, Tanya M.
AU - Orlowski, Robert Z.
AU - Shain, Kenneth H.
AU - Cowan, Andrew J.
AU - Murphy, Sean
AU - Lutska, Yana
AU - Pei, Huiling
AU - Ukropec, Jon
AU - Vermeulen, Jessica
AU - Boer, Carla de
AU - Hoehn, Daniela
AU - Lin, Thomas S.
AU - Richardson, Paul G.
N1 - Funding Information:
This work was supported by research funding from Janssen Oncology.
Funding Information:
Conflict-of-interest disclosure: P.M.V. served in a consultancy or advisory role and received honoraria from Adaptive Biotechnologies, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and TeneoBio; served in a consultancy or advisory role for Novartis, and Oncopeptides; served on a speakers’ bureau for Janssen and Amgen; and received research funding from Amgen, Celgene, Janssen, GlaxoSmithKline, Takeda, and TeneoBio. J.L.K. has held membership on an entity’s board of directors or advisory committee for Pharmacyclics and Karyopharm; has received honoraria from Janssen; served as a consultant for AbbVie, Takeda, Celgene, Amgen, Bristol-Myers Squibb, Incyte, and TG Therapeutics; and is an employee of Winship Cancer Institute of Emory University. D.W.S. served in a consultancy or advisory role for Amgen, Celgene, and Janssen; and received honoraria from Celgene. B.R. has served as a consultant for Incyte, Takeda, and Seattle Genetics; received honoraria from Celgene, Incyte, Takeda, and Seattle Genetics; and served on a speakers’ bureau for Celgene. C.R. has served in a consultancy role or on a speakers’ bureau for Celgene, Takeda, Janssen, Kite, Sanofi, and Bristol-Myers Squibb. A.C. has received research funding from, served as a consultant for, and served on an advisory board for Janssen, Celgene, Novartis, and Amgen; has served in a consultancy role for Bristol-Myers Squibb; has served on an advisory board for Karyopharm, Sanofi, and Oncopeptides; has received research funding and served on an advisory board for Seattle Genetics and Millennium Pharmaceuticals/Takeda; and has received research funding from Pharmacyclics. R.S. has served on an advisory committee for Janssen and on an advisory board for Sanofi. L.J.C. has received research funding from Janssen, Celgene, GlaxoSmithKline, and Amgen; received honoraria from Amgen, Celgene, Sanofi, GlaxoSmithKline, and Janssen; has served in a consultancy or advisory role for AbbVie, Amgen, Celgene, Sanofi, GlaxoSmithKline, and Karyopharm; and has served on a speakers’ bureau for Amgen, Sanofi, and Janssen. L.D.A. has served in a consultancy or advisory role for, served on a speakers’ bureau for, and received honoraria from Celgene, Takeda, Janssen, and Amgen. N.S. has received research funding from Celgene, Janssen, Bluebird Bio, Sutro Biopharma, and Poseida; has served in an advisory role or held membership on an entity’s board of directors for Bristol-Myers Squibb, Amgen, Kite, Nkarta, TeneoBio, Genentech, Seattle Genetics, Oncopeptides, Karyopharm, Surface Oncology, Precision BioSciences, GlaxoSmithKline, Nektar, Amgen, Indapta Therapeutics, and Sanofi; owns stock in Indapta Therapeutics; and has received research funding from Celgene, Janssen, Bluebird Bio, and Sutro Biopharma. Y.A.E. has served on a speakers’ bureau for Janssen; received honoraria from and served on an independent adjudication committee for Takeda; and served on an advisory board and speakers’ bureau for Akcea. S.A.H. has served in a consultancy or advisory role for and received honoraria from Adaptive Biotechnologies, Bristol-Myers Squibb, Celgene, Genentech, Oncopep-tides, Sorrento, and Takeda; and has received research funding from Oncopeptides. C.C. has received honoraria from Takeda and Celgene; has served as a consultant for Celgene; and has received research funding from Takeda, Janssen, and Celgene. A.J. served as a consultant for, received honoraria from, or held membership on an entity’s board of directors or advisory committee for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm Therapeutics, Millennium Pharmaceuticals, Sanofi, SkylineDx, and Takeda; and has served as a consultant for and received honoraria from Adaptive Biotechnologies and Juno. T.M.W. has received research funding from Janssen and served as a consultant for Carevive. R.Z.O. has received honoraria from or held membership on an entity’s board of directors or advisory committees for Amgen, Janssen, Bristol-Myers Squibb, Kite Pharma, Celgene, Ionis Pharmaceuticals, Legend Biotech, Molecular Partners, Sanofi-Aventis, Servier, Takeda, and Pharmaceuticals North America; and received research funding from Amgen, BioTheryX, and Spectrum Pharmaceuticals. K.H.S. has received research funding from AbbVie; has served as a consultant for Adaptive Biotechnologies; and has held membership on an entity’s board of directors or served in an advisory role for Celgene, Bristol-Myers Squibb, Amgen, Takeda, Janssen, and Sanofi Genzyme. A.J.C. has received research funding from and served as a consultant for Janssen and Celgene; has received research funding from AbbVie and Juno Therapeutics, a subsidiary of Celgene; and served in a consultancy role for Cellectar and Sanofi. Y.L. is an employee of Janssen. S.M., H.P., J.U., J.V., C.d.B., D.H., and T.S.L. are employees of Janssen and have equity ownership. P.G.R. has received research funding from Oncopeptides, Celgene, Takeda, and Bristol-Myers Squibb; and has served as a member of an advisory committee or received honoraria from Karyopharm, Oncopep-tides, Celgene, Takeda, Amgen, Janssen, and Sanofi. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/8/20
Y1 - 2020/8/20
N2 - Lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) is standard frontline therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab (D) to RVd (D-RVd) in transplant-eligible NDMM patients was evaluated. Patients (N 5 207) were randomized 1:1 to D-RVd or RVd induction (4 cycles), ASCT, D-RVd or RVd consolidation (2 cycles), and lenalidomide or lenalidomide plus D maintenance (26 cycles). The primary end point, stringent complete response (sCR) rate by the end of post-ASCT consolidation, favored D-RVd vs RVd (42.4% vs 32.0%; odds ratio, 1.57; 95% confidence interval, 0.87-2.82; 1-sided P 5 .068) and met the prespecified 1-sided a of 0.10. With longer follow-up (median, 22.1 months), responses deepened; sCR rates improved for D-RVd vs RVd (62.6% vs 45.4%; P 5 .0177), as did minimal residual disease (MRD) negativity (1025 threshold) rates in the intent-to-treat population (51.0% vs 20.4%; P < .0001). Four patients (3.8%) in the D-RVd group and 7 patients (6.8%) in the RVd group progressed; respective 24-month progression-free survival rates were 95.8% and 89.8%. Grade 3/4 hematologic adverse events were more common with D-RVd. More infections occurred with D-RVd, but grade 3/4 infection rates were similar. Median CD341 cell yield was 8.2 3 106/kg for D-RVd and 9.4 3 106/kg for RVd, although plerixafor use was more common with D-RVd. Median times to neutrophil and platelet engraftment were comparable. Daratumumab with RVd induction and consolidation improved depth of response in patients with transplant-eligible NDMM, with no new safety concerns. This trial was registered at www.clinicaltrials.gov as #NCT02874742. (Blood.
AB - Lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) is standard frontline therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab (D) to RVd (D-RVd) in transplant-eligible NDMM patients was evaluated. Patients (N 5 207) were randomized 1:1 to D-RVd or RVd induction (4 cycles), ASCT, D-RVd or RVd consolidation (2 cycles), and lenalidomide or lenalidomide plus D maintenance (26 cycles). The primary end point, stringent complete response (sCR) rate by the end of post-ASCT consolidation, favored D-RVd vs RVd (42.4% vs 32.0%; odds ratio, 1.57; 95% confidence interval, 0.87-2.82; 1-sided P 5 .068) and met the prespecified 1-sided a of 0.10. With longer follow-up (median, 22.1 months), responses deepened; sCR rates improved for D-RVd vs RVd (62.6% vs 45.4%; P 5 .0177), as did minimal residual disease (MRD) negativity (1025 threshold) rates in the intent-to-treat population (51.0% vs 20.4%; P < .0001). Four patients (3.8%) in the D-RVd group and 7 patients (6.8%) in the RVd group progressed; respective 24-month progression-free survival rates were 95.8% and 89.8%. Grade 3/4 hematologic adverse events were more common with D-RVd. More infections occurred with D-RVd, but grade 3/4 infection rates were similar. Median CD341 cell yield was 8.2 3 106/kg for D-RVd and 9.4 3 106/kg for RVd, although plerixafor use was more common with D-RVd. Median times to neutrophil and platelet engraftment were comparable. Daratumumab with RVd induction and consolidation improved depth of response in patients with transplant-eligible NDMM, with no new safety concerns. This trial was registered at www.clinicaltrials.gov as #NCT02874742. (Blood.
UR - http://www.scopus.com/inward/record.url?scp=85087138059&partnerID=8YFLogxK
U2 - 10.1182/blood.2020005288
DO - 10.1182/blood.2020005288
M3 - Article
C2 - 32325490
AN - SCOPUS:85087138059
SN - 0006-4971
VL - 136
SP - 936
EP - 945
JO - Blood
JF - Blood
IS - 8
ER -