Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma

Summary

The purpose of this study is to determine if the addition of daratumumab to lenalidomide-bortezomib-dexamethasone (RVd) will increase the proportion of participants achieving stringent complete response (sCR), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of post autologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone.

Timeline

Start

2016-08-29

Primary completion

2019-01-25

Completion

2022-04-08

Outcome

Met primary endpoint

paper 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%; PMID 32325490 ↗

paper 1-sided P = .068) and met the prespecified 1-sided α of 0.10. PMID 32325490 ↗

Publications

• Voorhees PM, Sborov DW, Laubach J, Kaufman JL, Reeves B, Rodriguez C, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Dinner S, Gries KS, Pei H, Cortoos A, Patel S, Lin TS, Usmani SZ, Richardson PG. A plain language summary of the final analysis of the GRIFFIN study of daratumumab plus lenalidomide, bortezomib, and dexamethasone for people with newly diagnosed multiple myeloma. Future Oncol. 2025 Jan;21(1):25-49. doi: 10.1080/14796694.2024.2408909. Epub 2024 Oct 25.
• Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, Hulin C, Antonioli E, Leleu X, Mangiacavalli S, Perrot A, Cavo M, Belotti A, Broijl A, Gay F, Mina R, van de Donk NWCJ, Katodritou E, Schjesvold F, Balari AS, Rosinol L, Delforge M, Roeloffzen W, Silzle T, Vangsted A, Einsele H, Spencer A, Hajek R, Jurczyszyn A, Lonergan S, Ahmadi T, Liu Y, Wang J, Vieyra D, van Brummelen EMJ, Vanquickelberghe V, Sitthi-Amorn A, de Boer CJ, Carson R, Rodriguez-Otero P, Blade J, Moreau P. A plain language summary of the PERSEUS study of daratumumab plus bortezomib, lenalidomide, and dexamethasone for treating newly diagnosed multiple myeloma. Future Oncol. 2024;20(38):3043-3063. doi: 10.1080/14796694.2024.2394323. Epub 2024 Sep 17.
• Chari A, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Voorhees PM, Usmani SZ, Richardson PG. Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN. Blood Cancer J. 2024 Jul 8;14(1):107. doi: 10.1038/s41408-024-01088-6.
• Callander NS, Silbermann R, Kaufman JL, Godby KN, Laubach J, Schmidt TM, Sborov DW, Medvedova E, Reeves B, Dhakal B, Rodriguez C, Chhabra S, Chari A, Bal S, Anderson LD Jr, Dholaria BR, Nathwani N, Hari P, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Giri S, Costa LJ, Usmani SZ, Richardson PG, Voorhees PM. Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk. Blood Cancer J. 2024 Apr 22;14(1):69. doi: 10.1038/s41408-024-01030-w.
• Silbermann R, Laubach J, Kaufman JL, Sborov DW, Reeves B, Rodriguez C, Chari A, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Orlowski RZ, Shain KH, Cowan AJ, Gries KS, Pei H, Cortoos A, Patel S, Lin TS, Voorhees PM, Usmani SZ, Richardson PG. Health-related quality of life in transplant-eligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, bortezomib, and dexamethasone: Patient-reported outcomes from GRIFFIN. Am J Hematol. 2024 Jul;99(7):1257-1268. doi: 10.1002/ajh.27326. Epub 2024 Apr 15.
• Voorhees PM, Sborov DW, Laubach J, Kaufman JL, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Dinner S, Pei H, Cortoos A, Patel S, Lin TS, Usmani SZ, Richardson PG. Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial. Lancet Haematol. 2023 Oct;10(10):e825-e837. doi: 10.1016/S2352-3026(23)00217-X. Epub 2023 Sep 11.
• Nooka AK, Kaufman JL, Rodriguez C, Jakubowiak A, Efebera Y, Reeves B, Wildes T, Holstein SA, Anderson LD Jr, Badros A, Shune L, Chari A, Pei H, Cortoos A, Patel S, Lin TS, Richardson PG, Voorhees P. A plain language summary of daratumumab plus lenalidomide/bortezomib/dexamethasone in transplant-eligible Black patients with newly diagnosed multiple myeloma in the GRIFFIN study. Future Oncol. 2022 Dec;18(40):4443-4456. doi: 10.2217/fon-2022-0775. Epub 2023 Feb 17.
• Sborov DW, Baljevic M, Reeves B, Laubach J, Efebera YA, Rodriguez C, Costa LJ, Chari A, Silbermann R, Holstein SA, Anderson LD Jr, Kaufman JL, Shah N, Pei H, Patel S, Cortoos A, Bartlett JB, Vermeulen J, Lin TS, Voorhees PM, Richardson PG. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the GRIFFIN study. Br J Haematol. 2022 Nov;199(3):355-365. doi: 10.1111/bjh.18432. Epub 2022 Sep 16.
• Swan D, Henderson R, McEllistrim C, Naicker SD, Quinn J, Cahill MR, Mykytiv V, Lenihan E, Mulvaney E, Nolan M, Parker I, Natoni A, Lynch K, Ryan AE, Szegezdi E, Krawczyk J, Murphy P, O'Dwyer M. CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment. Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):847-852. doi: 10.1016/j.clml.2022.07.011. Epub 2022 Jul 21.
• Voorhees PM, Rodriguez C, Reeves B, Nathwani N, Costa LJ, Lutska Y, Bobba P, Hoehn D, Pei H, Ukropec J, Qi M, Lin TS, Richardson PG. Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN. Blood Adv. 2021 Feb 23;5(4):1092-1096. doi: 10.1182/bloodadvances.2020003642.
• Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Murphy S, Lutska Y, Pei H, Ukropec J, Vermeulen J, de Boer C, Hoehn D, Lin TS, Richardson PG. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020 Aug 20;136(8):936-945. doi: 10.1182/blood.2020005288.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Bortezomib	Small molecule	1.3 mg/m2	Subcutaneous
Subject	Daratumumab	Monoclonal antibody	16 mg/kg	Intravenous
Subject	Dexamethasone	Small molecule	40 mg	Oral
Subject	Lenalidomide	Other / unclassified	10 mg	Oral

Indications