Results of the CARDAMON trial indicate that, although carfilzomib maintenance was feasible and yielded higher MRD negativity rates at 6 months with ASCT than with consolidation, it was associated with a higher incidence of grade ≥3 adverse events and discontinuations after ASCT.
The CARDAMON trial investigated carfilzomib maintenance following carfilzomib/cyclophosphamide/dexamethasone (KCd) induction plus either autologous stem-cell transplantation (ASCT) or KCd consolidation in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Results of the trial were presented at the 2021 International Myeloma Workshop and summarized here.
Eligible patients received induction therapy consisting of 4 cycles of KCd (carfilzomib 20/56 mg/m2 biweekly; cyclophosphamide 500 mg on days 1, 8, and 15; and dexamethasone 40 mg weekly), and then randomized 1:1 to undergo ASCT or receive 4 cycles of KCd consolidation, followed by 18 cycles of carfilzomib maintenance (56 mg/m2 on days 1, 8, and 15). Minimal residual disease (MRD, 10–5) was assessed using flow cytometry after induction, premaintenance, and at 6-month maintenance. Primary end points were very good partial response or better after induction and 2-year progression-free survival (PFS) from randomization. Secondary end points included improvements in disease response and MRD conversion following ASCT/consolidation and maintenance.
A total of 218 patients were randomized to either undergo ASCT or receive KCd consolidation. A total of 196 patients received carfilzomib maintenance. Of these, 99 patients were in the ASCT arm and 97 were in the consolidation arm. Patients received a median of 16 cycles over a median of 15.9 months.
Carfilzomib maintenance treatment interruptions as a result of COVID-19 occurred in 41 patients (8 in the ASCT arm and 6 in the consolidation arm) and treatment discontinuation caused by COVID-19 occurred in 15 patients (9 in ASCT and 6 in consolidation). Carfilzomib maintenance discontinuations caused by progressive disease occurred in 14.1% of patients in the ASCT arm and 22.7% of patients in the consolidation arm. Carfilzomib maintenance discontinuations as a result of adverse events (AEs) were reported in 7.1% of patients in the ASCT arm and 4.1% of patients in the consolidation arm. Most common AEs reported were hypertension and infections. A significantly higher incidence of grade ≥3 AEs were reported in the ASCT cohort compared with the consolidation cohort (P = .01). Whereas the rate of patient–clinician withdrawals from maintenance were low overall, they occurred more often in the ASCT cohort (9.1% vs 1%, respectively).
Consolidation therapy with KCd failed to show noninferiority to ASCT, with median PFS for ASCT not yet reached versus 3.4 years for consolidation and a 6.5% difference in 2-year PFS (70% confidence interval, 1.0%-11.1%). After ASCT/consolidation, a significantly higher MRD negativity rate was achieved by the ASCT cohort compared with the consolidation cohort (53.6% vs 35.1%, respectively; P = .01), with patients who achieved MRD negativity showing a significant prolongation of PFS compared with the MRD-positive cohort (P = .002). Patients who achieved MRD negativity at 6 months after maintenance had significantly longer PFS than patients with MRD-positive disease (P = .004), with significantly higher MRD negativity rates achieved by patients in the ASCT cohort (58.1% vs 40.5%, respectively; P = .02). Overall, 27.8% of patients with MRD positivity converted to MRD negativity after ASCT/consolidation and 23.5% converted during maintenance, with a higher proportion converting after ASCT than after consolidation in both cases. There was no difference in maintenance of MRD negativity over the first 6 months between the ASCT and consolidation arms (P = .3).
These results indicate that although carfilzomib maintenance was feasible and yielded higher MRD negativity rates at 6 months with ASCT than with consolidation, it was associated with higher incidence of grade ≥3 AEs and discontinuations as a result of AEs after ASCT.
Source: Popat R, Wilson W, Camilleri M, et al. CARDAMON: carfilzomib (K) maintenance following autologous stem cell transplant (ASCT) or carfilzomib-cyclophosphamide-dexamethasone (KCd) consolidation for newly diagnosed (NDTE) multiple myeloma (MM). Clin Lymphoma Myeloma Leuk. 2021;21(suppl 2):S2-S3.
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