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Clinical Trial
. 2019 May;185(3):492-502.
doi: 10.1111/bjh.15806. Epub 2019 Mar 3.

Daratumumab, bortezomib, cyclophosphamide and dexamethasone in newly diagnosed and relapsed multiple myeloma: LYRA study

Habte Yimer  1 , Jason Melear  2 , Edward Faber  3 , William I Bensinger  4 , John M Burke  5 , Mohit Narang  6 , Don Stevens  7 , Sriya Gunawardena  8 , Yana Lutska  8 , Keqin Qi  9 , Jon Ukropec  10 , Ming Qi  11 , Thomas S Lin  8 , Robert M Rifkin  12
Affiliations
Clinical Trial

Daratumumab, bortezomib, cyclophosphamide and dexamethasone in newly diagnosed and relapsed multiple myeloma: LYRA study

Habte Yimer et al. Br J Haematol. 2019 May.

Abstract

This United States community study evaluated the combination of daratumumab, bortezomib, cyclophosphamide and dexamethasone (D-VCd) in newly diagnosed multiple myeloma (NDMM) and relapsed multiple myeloma (RMM). Patients received 4-8 induction cycles of bortezomib 1·5 mg/m2 , cyclophosphamide 300 mg/m2 and dexamethasone 40 mg weekly. Intravenous daratumumab 16 mg/kg was administered as approved except for a split-first dose in Cycle 1. Eligible patients underwent autologous stem cell transplantation. All patients received ≤12 daratumumab maintenance doses monthly. Eighty-six NDMM and 14 RMM patients received ≥1 treatment dose. In NDMM patients, very good partial response or better (≥VGPR) and overall response rates after 4 induction cycles were 44% (primary endpoint) and 79%, respectively, and 56% and 81% at end of induction. The 12-month progression-free survival (PFS) rate was 87%. Efficacy was also observed in RMM patients. Fatigue (59%) and neutropenia (13%) were the most frequent treatment-emergent adverse event (TEAE) and grade 3/4 TEAE, respectively. Infusion reactions occurred in 54% of patients, primarily during the first dose, and were mild (2% grade 3). The first 2 daratumumab infusions were 4·5 and 3·8 h (median). Overall, D-VCd was well tolerated, split-first daratumumab dosing was feasible, the ≥VGPR rate after 4 cycles was 44% and the 1-year PFS rate was 87%.

Keywords: LYRA; bortezomib; cyclophosphamide; daratumumab; multiple myeloma.

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Conflict of interest statement

HY served on advisory boards for Seattle Genetics and Celgene; served as a speaker for Janssen, AstraZeneca and Seattle Genetics; owns stock in Epizyme, Clovis Oncology and Puma Biotechnology. JM served on a speakers’ bureau for Janssen. EF served on advisory boards for and received honoraria from Amgen, Cardinal Health, Celgene and Kite. WIB served on speakers’ bureaus for Janssen and Takeda and served on advisory boards for Janssen. JMB served as a consultant for Celgene, Bayer, Genentech, Gilead, AbbVie, Seattle Genetics and Tempus Labs, and served on a speakers’ bureau for Seattle Genetics. MN received speaker fees or honoraria from Janssen and Celgene and served as a consultant for Celgene. DS is a member on an entity's board of directors or advisory committee for Bayer and served as a consultant for Bayer. SG, YL, KQ, JU, MQ and TSL are employees of Janssen. RMR served as a consultant for Amgen, Boehringer Ingelheim, Celgene, EMD Serono, Sandoz and Takeda, and holds equity in McKesson.

Figures

Figure 1
Figure 1
LYRA study design. aRange of 4–8 induction cycles due to differences in local standard of care across study sites and enrolment of both transplant eligible, transplant ineligible and relapsed patients. bIn Cycle 1, 20 mg dexamethasone was given on Days 1 and 2 and weekly thereafter. cIn patients who underwent ASCT, maintenance therapy was to begin approximately 90 days after ASCT. ASCT, autologous stem cell transplantation; HDT, high‐dose therapy; IV, intravenously; PO, orally; SC, subcutaneously; VCd, bortezomib, cyclophosphamide and dexamethasone.
Figure 2
Figure 2
ORR in Cycles 1–4 and end of induction (A) and progression‐free survival (B) in newly diagnosed multiple myeloma patients treated with daratumumab plus VCd. Responses may not add up to the total response rates due to rounding. CR, complete response; ORR, overall response rate; PR, partial response; VCd, bortezomib, cyclophosphamide and dexamethasone; VGPR, very good partial response.
See this image and copyright information in PMC

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