Frontline KCyd safe, effective in high-risk multiple myeloma

In transplant-eligible patients with high-risk newly diagnosed multiple myeloma (NDMM), frontline treatment with carfilzomib, cyclophosphamide, and dexamethasone (KCyd) is safe and effective, inducing high rates of treatment response without a heavy burden of adverse events (AEs), according to a recent Singapore study.

“The demonstration of a good progression-free survival (PFS) and overall survival (OS) using KCyd supports the notion that upfront strategies using two or more novel agents may not always be necessary for every patient especially when the cost is a key consideration,” the researchers said, adding that their findings continue to support the relevance of cyclophosphamide in the era of novel therapies.

Thirty NDMM patients (median age 61.9 years) participated in the study and received six 28-day induction cycles of KCyd. Those who responded to treatment underwent autologous stem cell transplant (ASCT) after six induction cycles. Those who achieved at least very good partial remission (VGPR) were subjected to minimal residual disease (MRD) analysis. The primary outcome was PFS, while OS and MRD status were set as secondary outcomes.

Ten patients (33.3 percent) achieved complete response (CR) after treatment induction, 12 (52.2 percent) after ASCT, and 15 (71.4 percent) after consolidation. Corresponding rates of ≥VGPR were 63.3 percent, 91.3 percent, and 100 percent. Twenty-one patients (71 percent) were able to complete the treatment plan, from induction, through ASCT, and up to consolidation. [Blood Cancer J 2021;11:150]

Twelve of the treatment completers (57.1 percent) achieved MRD and were put on 36-mg/m² carfilzomib maintenance. The remaining nine patients were MRD-negative and were managed expectantly.

Over a median follow-up duration of 43.4 months, PFS was calculated to be 40.3 months while OS was 49.5 months. PFS was comparable between those who did vs did not achieve MRD (p=0.43).

In terms of safety, 13 patients developed haematologic treatment-emergent AEs (TEAEs), yielding an incidence rate of 43.3 percent. Other common TEAEs included pneumonia, infections, acute kidney injuries, and gastrointestinal side effects. Of note, six TEAEs led to treatment discontinuation: three cases of thrombotic microangiography (TMA) and one case each of non-ST elevation myocardial infarction (NSTEMI), cytomegalovirus retinitis, and acute pulmonary oedema (APO).

Following discontinuation, all TMA cases were resolved. Both NSTEMI and APO episodes occurred during induction, and the patients were removed from the study. The average relative dose intensity of carfilzomib was 82.4 percent during induction and 86.2 percent during consolidation.

“Although acknowledging the combination of proteasome inhibitors and immunomodulatory drug rightly remains the current standard of care, results from our study support continued investigation of KCyd as a more economical and efficacious alternative as a first-line treatment regimen (especially when generic preparations are not available), as compared with regimens such as Velcade-Revlimid-dexamethasone, in NDMM,” the researchers said.