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.
- 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.