Final analysis results of the LYRA study demonstrated that daratumumab in combination with CyBorD induction therapy and as maintenance yielded durable and deep responses in patients with newly diagnosed or recurrent MM irrespective of ASCT status, with no new safety signals.
The community practice–based, phase 2, single-arm LYRA trial (NCT02951819) evaluated the anti-CD38 monoclonal antibody daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) as an immunomodulatory drug–sparing induction regimen in patients with multiple myeloma (MM). Results of the final analysis of the LYRA trial were presented at the 2021 ASCO Annual Meeting and summarized here.
The study enrolled patients aged ≥18 years with MM per International Myeloma Working Group criteria and who have received ≤1 previous lines of therapy. Eligible patients received 4 to 8 induction cycles of daratumumab plus CyBorD (cyclophosphamide 300 mg/m2 orally [PO] every week; bortezomib 1.5 mg/m2 subcutaneous on days 1, 8, and 15; dexamethasone 40 mg PO or intravenously [IV] every week, every 28 days; daratumumab IV 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg every week cycle 1 day 8 through cycle 2, 16 mg/kg every 2 weeks in cycles 3-6, and 16 mg/kg every 4 weeks in cycles 7-8). After induction, eligible patients received autologous stem-cell transplantation (ASCT). Following induction therapy and/or ASCT, all patients received up to 12 maintenance cycles with daratumumab 16 mg/kg IV every 4 weeks and were followed for up to 36 months.
A total of 101 patients were enrolled in the study. Of these, 87 patients had newly diagnosed MM (NDMM) and 14 patients had relapsed MM (RMM). Thirty-six percent of patients had high-risk cytogenetics. In the NDMM cohort, patients received a median of 6 induction treatment cycles, 44.8% of patients underwent ASCT, and 72.4% completed 12 months of maintenance therapy. Among RMM patients, 7.1% underwent ASCT and 50.0% completed 12 months of maintenance.
Response rates deepened with additional cycles of the daratumumab plus CyBorD induction. At the end of the study in the NDMM cohort, 82.1% of patients who had ASCT achieved at least a very good partial response (VGPR) and 48.7% achieved at least a complete response (CR). VGPR and CR were 70.2% and 29.8%, respectively, in patients who did not undergo ASCT. In the NDMM cohort, with a median follow-up of 35.7 months, median progression-free survival (PFS) and overall survival were not reached regardless of transplant status. Among NDMM patients, estimated 36-month PFS rates were 69.3% in patients who underwent ASCT and 72.6% in those who did not; estimated 36-month overall survival rates were 94.9% and 84.3%, respectively. Among RMM patients, at least VGPR rate at the end of the study was 71.4%, at least CR rate was 64.3%, estimated 36-month PFS rate was 31.7% (median PFS was 21.7 months), and estimated 36-month overall survival rate was 50%.
In the overall population, grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 62.0% of patients. The most common (14.0%) TEAE that occurred in ≥10% of patients was neutropenia. Serious TEAEs occurred in 33.0% of patients in the NDMM cohort and 36% in the RMM cohort; the most common serious TEAEs were pneumonia (RMM cohort, 14.0%) and pulmonary embolism (2.3% in each cohort). Treatment discontinuation caused by TEAEs occurred in 7 patients in the NDMM cohort and 1 patient in the RMM cohort. Cardiac-related TEAEs occurred in 16.3% of patients in the NDMM cohort, and none in the RMM cohort. Infusion-related reactions occurred in 56.0% of patients in the NDMM cohort and 57% of patients in the RMM cohort.
Final analysis results of the LYRA study demonstrated that daratumumab in combination with CyBorD induction therapy and as maintenance yielded durable and deep responses in patients with NDMM or RMM irrespective of ASCT status, with no new safety signals.
Source: Rifkin RM, Melear JM, Faber E, et al. Daratumumab (DARA) maintenance therapy following DARA + cyclophosphamide, bortezomib, and dexamethasone (CyBorD) induction therapy in multiple myeloma (MM): end-of-study analysis of LYRA. J Clin Oncol. 2021;39(suppl 15):Abstract 8035.