An 8-cycle transplant-based regimen with carfilzomib, lenalidomide, and dexamethasone (KRd) as induction and consolidation followed by 1-year lenalidomide maintenance was highly effective in patients with newly diagnosed multiple myeloma (NDMM), researchers reported in a study published in Blood.
The open-label, phase 2 study (ClinicalTrials.gov Identifier: NCT02405364) was conducted at 10 centers in France and enrolled patients from March 2014 to November 2014. Patients were aged younger than 66 years with symptomatic and measurable NDMM, had not received any previous myeloma therapy, and were eligible for autologous stem cell transplantation.
All patients received four 28-day cycles of intravenous carfilzomib 20 mg/m2 to 36 mg/m2, oral lenalidomide 25 mg, and oral dexamethasone 20 mg. Study patients who were nonprogressive could receive consolidation therapy with four 28-day KRd cycles 2 months after hematologic recovery. The stringent complete response (sCR) rate at the completion of consolidation was the primary endpoint.
A total of 46 patients were included (median age, 56 years [interquartile range, 50-62]; 70% men) and received at least 1 dose of treatment during the induction phase. Of the cohort, 42 patients underwent transplantation, 41 entered the consolidation phase, and 40 entered the maintenance phase of 1 year of lenalidomide (10 mg).
After completion of consolidation therapy, 26 patients achieved an sCR (61.9%; 90% CI, 48.0-74.4; P =.0034). The sCR rate was 56.5% (90% CI, 43.4-69.0; P =.0172), based on a sensitivity analysis of the primary endpoint. In addition, 27 participants (64.3%) were at least in complete response, and 25 (92.6%) had undetectable minimal residual disease (MRD) with use of multiparameter flow cytometry (2.5 × 10-5) and 17 (63.0%) with next generation sequencing (10-6).
The median follow-up was 60.5 months (58.7-62.1); 21 patients progressed and 10 died as of November 2019. The median progression-free survival was 56.4 months (95% CI, 43.5-not evaluable), and the median overall survival was not reached.
No KRd-related deaths were observed, and 4 patients (8.7%) permanently discontinued combined treatment because of serious adverse events (SAEs); 3 during induction and 1 posttransplant.
A total of 56 SAEs were reported in 31 (67.4%) of the patients including 23 treatment-emergent SAEs (TEAEs) among 19 (41.3%) of those patients, infections among 12 (26.1%) of the patients, and musculoskeletal disorders among 9 (19.6%) of the study patients. Also, at least 1 grade 3 to 4 TEAE occurred in 45 (97.8%) of the patients. Hematologic toxicities (induction, 26.1%; consolidation, 75.6%) and infections (induction, 19.6%; consolidation: 2.4%) were the most frequently occurring grade 3 to 4 TEAEs.
“Responses are rapid and deep with improvement at each step including deepening rates of undetectable MRD,” the researchers commented. “The safety profile is acceptable especially if patients undergo regular, close monitoring to minimize cardiovascular and thrombotic toxicities,” they concluded.
Disclosures: This clinical trial was supported by Amgen and Celgene. Several of the study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Roussel M, Lauwers-Cances V, Wuilleme S, et al. Upfront carfilzomib, lenalidomide, dexamethasone with transplant in multiple myeloma patients, the IFM KRd final results. Blood. Published online April 7, 2021. doi:10.1182/blood.2021010744