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Daratumumab + Cyclophosphamide, Bortezomib, and Dexamethasone Induction Followed by Daratumumab Maintenance Achieved Durable Responses in Patients with RRMM and NDMM

2022 Year in Review - Multiple Myeloma

Final results from LYRA demonstrated robust responses with dara + CyBorD induction, which deepened with dara maintenance.

The LYRA study was a multicenter, phase 2, single-arm study which evaluated the safety and efficacy of daratumumab (dara) in combination with cyclophosphamide plus bortezomib and dexamethasone (CyBorD) in patients with newly diagnosed multiple myeloma (NDMM) and relapsed/refractory multiple myeloma (RRMM). The previously reported primary analysis demonstrated efficacy and tolerability with dara + CyBorD in both patient populations. In a 2022 publication, Yimer and colleagues reported results from the final, end-of-study analysis of LYRA after all patients completed the study therapy, were followed for 36 months, withdrew, or died.

Patients received dara + CyBorD induction therapy and up to 12 monthly doses of dara monotherapy maintenance treatment; those eligible could receive high-dose therapy (HDT) and autologous stem-cell transplant (ASCT). RRMM patients were allowed to have received 1 line of therapy, including an induction regimen followed by HDT and ASCT and single-agent maintenance therapy, but could not be refractory to any proteasome inhibitor (PI) or combination of a PI and immunomodulatory agent. The primary end point was the rate of very good partial response or better (≥VGPR) after 4 cycles of dara + CyBorD induction therapy. Secondary end points were overall response rate, time to ≥VGPR, time to and duration of response, progression-free survival (PFS), and overall survival (OS).

Eighty-seven NDMM patients were enrolled, 39 underwent transplant, and 63 completed maintenance. The median follow-up for NDMM patients was 35.7 months. The ≥VGPR rate after 4 cycles of dara + CyBorD induction in NDMM patients was 44.2%, and response rates increased with additional induction cycles and dara maintenance. ≥VGPR rate by the end of induction in the 39 patients who underwent transplant was 64.1%, which rose to 82.1% by the end of the study. For patients who did not receive transplant (n = 47), ≥VGPR at the end of induction was 63.8%, which rose to 70.2% by the end of the study. Dara maintenance increased rates of overall response and complete response or better (≥CR). The ≥CR rate in transplanted NDMM patients was 5.1% at the end of induction and 48.7% at the end of the study. The ≥CR rate in non-transplant patients was 17.0% at the end of induction and 29.8% at the end of the study. Median PFS was not reached in NDMM patients, and estimated median 36-month PFS rates were 69.3% in transplanted patients and 72.6% for non-transplanted patients.

Fourteen RRMM patients were enrolled with a median follow-up of 35.3 months; 13 patients completed 4 cycles of induction and 10 completed 5 to 8 cycles of induction. The rate of ≥VGPR after 4 cycles was 57.1%, which increased to 71.4% by the end of the study. The rate of ≥CR was 28.6% at the end of induction and 64.3% at the end of the study. The median PFS in RRMM patients was 21.7 months and the median duration of response was 20.7 months. OS was not reached. The estimated 36-month PFS and OS rates were 31.7% and 50.0%, respectively.

Grade 3-4 treatment-emergent adverse events (TEAEs) occurred in 62.8% of NDMM patients and 57.1% of RRMM patients. Neutropenia was the most frequent grade 3-4 TEAE, occurring in 12.8% of NDMM and 21.4% of RRMM patients. Seven NDMM patients and 1 RRMM patient discontinued therapy due to TEAEs, and 1 patient in both groups experienced a TEAE leading to death. A total of 57.1% of RRMM and 55.8% of NDMM patients experienced infusion-related reactions. Although the RRMM cohort was limited by size, the final analysis of the LYRA study showed that dara + CyBorD induction followed by dara maintenance is well tolerated and effective for patients with NDMM and RRMM.


  1. Yimer H, Melear J, Faber E, et al. Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for multiple myeloma: final results of the LYRA study. Leuk Lymphoma. 2022;63:2383-2392.
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