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

Peter M. Voorhees, Jonathan L. Kaufman, Jacob Laubach, Douglas W. Sborov, Brandi Reeves, Cesar Rodriguez, Ajai Chari, Rebecca Silbermann, Luciano J. Costa, Larry D. Anderson, Nitya Nathwani, Nina Shah, Yvonne A. Efebera, Sarah A. Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M. Wildes, Robert Z. Orlowski, Kenneth H. Shain, Andrew J. CowanSean Murphy, Yana Lutska, Huiling Pei, Jon Ukropec, Jessica Vermeulen, Carla de Boer, Daniela Hoehn, Thomas S. Lin, Paul G. Richardson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)936-945
Number of pages10
JournalBlood
Volume136
Issue number8
DOIs
StatePublished - Aug 20 2020

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Voorhees, P. M., Kaufman, J. L., Laubach, J., Sborov, D. W., Reeves, B., Rodriguez, C., Chari, A., Silbermann, R., Costa, L. J., Anderson, L. D., Nathwani, N., Shah, N., Efebera, Y. A., Holstein, S. A., Costello, C., Jakubowiak, A., Wildes, T. M., Orlowski, R. Z., Shain, K. H., ... Richardson, P. G. (2020). Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood, 136(8), 936-945. https://doi.org/10.1182/blood.2020005288