MM logo

Daratumumab plus Cyclophosphamide, Bortezomib, Dexamethasone Well-Tolerated and Effective in Patients with RRMM and NDMM: The LYRA Study

The LYRA study was a multicenter, phase 2, single-arm study that evaluated the safety and efficacy of daratumumab in combination with cyclophosphamide, bortezomib, dexamethasone (CyBorD) in patients with newly diagnosed multiple myeloma (NDMM) or relapsed/refractory multiple myeloma (RRMM).

Patients received daratumumab plus CyBorD induction therapy and up to 12 monthly doses of daratumumab monotherapy maintenance treatment; those eligible could also receive high-dose therapy and autologous stem-cell transplant (ASCT). To be eligible, RRMM patients could have received 1 line of therapy, including an induction regimen followed by high-dose therapy and ASCT and single-agent maintenance therapy but could not be refractory to any proteasome inhibitor or the combination of a proteasome inhibitor and immunomodulatory agents. The primary end point was the rate of very good partial response or better (≥VGPR) after 4 cycles of daratumumab plus CyBorD induction therapy. Secondary end points were overall response rate, time to ≥VGPR, time to response, duration of response, progression-free survival (PFS), overall survival (OS), and safety and tolerability. The final analysis occurred when all patients completed a 36-month follow-up after the start of induction therapy, died, or withdrew from the study.

A total of 101 patients enrolled (87 patients with NDMM, 14 patients with RRMM), and 100 patients received ≥1 doses of the study treatment (86 patients with NDMM, 14 patients with RRMM).

The median follow-up for patients with NDMM was 35.7 months. Overall, 81 patients with NDMM completed ≥4 cycles of induction therapy, and 61 patients completed 5 to 8 cycles of induction. The ≥VGPR rate after 4 cycles of daratumumab plus CyBorD induction in patients with NDMM was 44.2%, and response rates increased with additional induction cycles and daratumumab maintenance. Of the NDMM patients, 39 underwent transplant, and the ≥VGPR rate by the end of induction in these patients was 64.1%, and this rate rose to 82.1% by the end of the study. For the 47 patients who did not receive transplant, the rate of ≥VGPR at the end of induction was 63.8%, which rose to 70.2% by the end of the study. Daratumumab 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 nontransplanted patients was 17.0% at the end of induction and 29.8% at the end of the study. Median PFS was not reached in the patients with NDMM, and estimated median 36-month PFS rates were 69.3% and 72.6% for transplanted and nontransplanted patients, respectively.

In patients with RRMM, median follow-up was 35.3 months. A total of 13 patients completed 4 cycles of induction therapy, and 10 patients completed 5 to 8 cycles. 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 patients with RRMM 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 patients with NDMM and 57.1% of patients with RRMM. The most frequent grade 3/4 TEAE was neutropenia in 12.8% of patients with NDMM and 21.4% of patients with RRMM. Therapy was discontinued in 7 patients with NDMM and 1 patient with RRMM due to TEAEs. In addition, 1 patient in each group experienced a TEAE leading to death. Infusion-related reactions occurred in 57.1% of patients with RRMM and 55.8% of patients with NDMM.

Although the RRMM cohort was limited by size, the final analysis of the LYRA study showed that daratumumab plus CyBorD induction followed by daratumumab maintenance was generally well-tolerated and effective in 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. 2022:1-10.

Related Articles

Subscribe Today!

To sign up for our free e-Newsletter or print publications, please enter your contact information below.

I'd like to receive:

OPM e-Newsletter
OPM print publication