Real-world effectiveness and safety of daratumumab, bortezomib and dexamethasone in relapsed/refractory multiple myeloma in Slovakia.

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) are limited. Daratumumab in combination with bortezomib and dexamethasone is a promising new treatment. The aim of this analysis was to assess the outcomes of daratumumab-bortezomib-dexamethasone (DVd) combination for the treatment of patients with RRMM in a real-world setting. All consecutive RRMM patients who received at least two cycles of DVd treatment between December 2016 and July 2020 were identified. We analyzed the clinical characteristics and survival of 47 patients treated at 7 Slovak centers outside of the clinical trials. The median age was 65 years (range, 35 to 83). The median (range) number of lines of therapy per patient was 3 (2-6). All patients were previously exposed to PIs (proteasome inhibitors) and IMIDs (immunomodulatory drugs), the majority of patients (70.2%) had double refractory (IMIDs and PI) disease and 72.3% of patients were refractory to their last therapy. Most patients presented with high-risk characteristics, including 25.6% adverse cytogenetics and 25.5% extramedullary disease. The majority of patients responded with an overall response rate of 78%, we found complete response in 3, very good partial response in 22, partial response in 12, minor response or stable disease in 9, and progressive disease in 1 patient. After a median follow-up period of 8 months, the median progression-free survival was 10 months. There was a longer progression-free survival in those with 2 vs. >2 prior treatments, with equally good effectivity in standard-risk and high-risk cytogenetic groups. The adverse events were usually mild, none leading to permanent drug interruptions. Daratumumab-bortezomib-based combinations are efficacious and safe regimens in RRMM patients in the real-world setting. This is the first analysis in Slovakia addressing the DVd combination outside of the clinical trial setting.

Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy.

BACKGROUND: We confirmed the benefit of addition of ixazomib to lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM) in unselected real-world population. We report the final analysis for overall survival (OS), second progression free survival (PFS-2), and the subanalysis of the outcomes in lenalidomide (LEN) pretreated and LEN refractory patients. METHODS: We assessed 344 patients with RRMM, treated with IRD (N = 127) or RD (N = 217). The data were acquired from the Czech Registry of Monoclonal Gammopathies (RMG). With prolonged follow-up (median 28.5 months), we determined the new primary endpoints OS, PFS and PFS-2. Secondary endpoints included the next therapeutic approach and the survival measures in LEN pretreated and LEN refractory patients. RESULTS: The final overall response rate (ORR) was 73.0% in the IRD cohort and 66.8% in the RD cohort. The difference in patients reaching ≥VGPR remained significant (38.1% vs. 26.3%, p = 0.028). Median PFS maintained significant improvement in the IRD cohort (17.5 vs. 12.5 months, p = 0.013) with better outcomes in patients with 1-3 prior relapses (22.3 vs. 12.7 months p = 0.003). In the whole cohort, median OS was for IRD vs. RD patients 40.9 vs. 27.1 months (p = 0.001), with further improvement within relapse 1-3 (51.7 vs. 27.8 months, p ˂ 0.001). The median PFS of LEN pretreated (N = 22) vs. LEN naive (N = 105) patients treated by IRD was 8.7 vs. 23.1 months (p = 0.001), and median OS was 13.2 vs. 51.7 months (p = 0.030). Most patients in both arms progressed and received further myeloma-specific therapy (63.0% in the IRD group and 53.9% in the RD group). Majority of patients received pomalidomide-based therapy or bortezomib based therapy. Significantly more patients with previous IRD vs. RD received subsequent monoclonal antibodies (daratumumab-16.3% vs. 4.3%, p = 0.0054; isatuximab 5.0% vs. 0.0%, p = 0.026) and carfilzomib (12.5 vs. 1.7%, p = 0.004). The median PFS-2 (progression free survival from the start of IRD/RD therapy until the second disease progression or death) was significantly longer in the IRD cohort (29.8 vs. 21.6 months, p = 0.016). There were no additional safety concerns in the extended follow-up. CONCLUSIONS: The IRD regimen is well tolerated, easy to administer, and with very good therapeutic outcomes. The survival measures in unsorted real-world population are comparable to the outcomes of the clinical trial. As expected, patients with LEN reatment have poorer outcomes than those who are LEN-naive. The PFS benefit of IRD vs. RD translated into significantly better PFS-2 and OS, but the outcomes must be accounted for imbalances in pretreatment group characteristics (especially younger age and stem cell transplant pretreatment), and in subsequent therapies.