Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial

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 w...

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Bibliographic Details
Published in:Blood 2020-08, Vol.136 (8), p.936-945
Main Authors: Voorhees, Peter M., Kaufman, Jonathan L., Laubach, Jacob, Sborov, Douglas W., Reeves, Brandi, Rodriguez, Cesar, Chari, Ajai, Silbermann, Rebecca, Costa, Luciano J., Anderson, Larry D., Nathwani, Nitya, Shah, Nina, Efebera, Yvonne A., Holstein, Sarah A., Costello, Caitlin, Jakubowiak, Andrzej, Wildes, Tanya M., Orlowski, Robert Z., Shain, Kenneth H., Cowan, Andrew J., Murphy, Sean, Lutska, Yana, Pei, Huiling, Ukropec, Jon, Vermeulen, Jessica, de Boer, Carla, Hoehn, Daniela, Lin, Thomas S., Richardson, Paul G.
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bortezomib - administration & dosage
Bortezomib - adverse effects
Clinical Trials and Observations
Combined Modality Therapy
Dexamethasone - administration & dosage
Female
Hematopoietic Stem Cell Transplantation
Humans
Lenalidomide - administration & dosage
Lenalidomide - adverse effects
Maintenance Chemotherapy - methods
Male
Middle Aged
Multiple Myeloma - drug therapy
Multiple Myeloma - mortality
Multiple Myeloma - pathology
Multiple Myeloma - therapy
Patient Selection
Transplantation, Autologous
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Summary: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 = 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 = .068) and met the prespecified 1-sided α 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 = .0177), as did minimal residual disease (MRD) negativity (10−5 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 CD34+ cell yield was 8.2 × 106/kg for D-RVd and 9.4 × 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. •D-RVd improved sCR rates and MRD negativity vs RVd, both of which deepened over time.•No new safety concerns were observed with D-RVd, and no clinically significant impact on stem cell mobilization or engraftment was noted. [Display omitted]
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.2020005288