Does the Addition of Cyclophosphamide to Bortezomib and Dexamethasone Improve Outcomes in Patients with MM and Renal Disease?

A study published in the Journal of Clinical Oncology assessed doublet versus triplet bortezomib-based therapy in patients with initial myeloma cast nephropathy and acute kidney injury (AKI) without the need for dialysis. The study found that triplet therapy “did not show any benefit … on renal recovery of patients with initial cast nephrology not requiring dialysis,” according to the authors.

In this multicenter, controlled study, patients were randomized to receive bortezomib and dexamethasone with (n=92; triplet) or without (n=92; doublet) cyclophosphamide. Among patients with less than 50% reduction of serum-free light chains (sFLCs) after three cycles, chemotherapy was reinforced with either cyclophosphamide or thalidomide.

Median patient age across both treatment cohorts was 68 years; serum creatinine levels were 305.5 µmol/L in those receiving bortezomib and dexamethasone alone versus 273.5 µmol/L in those receiving cyclophosphamide.

At three months, renal response rate (primary endpoint) did not differ among those who did and did not receive cyclophosphamide (47 vs. 41, respectively; relative risk [RR], 0.87; P=0.46). Very-good partial response (defined as free light chain reduction ≥90%) or more was achieved in 47 and 36 patients, respectively (RR, 0.76; P=0.10).

After one cycle of chemotherapy, 69 patients in the bortezomib and dexamethasone alone group and 67 patients in the cyclophosphamide combination cohort achieved sFLC level ≤500 mg/L.

“Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance,” the authors wrote. Serious adverse events occurred in 30 patients in the bortezomib and dexamethasone alone cohort and 40 patients in the cyclophosphamide group. At 12 months, 19 patients had died (nine in the bortezomib and dexamethasone alone group vs. 10 in the cyclophosphamide group arm); 10 deaths were related to multiple myeloma (MM) progression and three were due to infection.

During a median follow-up of 27 months, 43 patients in the bortezomib and dexamethasone alone group and 42 in the cyclophosphamide group switched to a new therapy.

“Patients with MM with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty,” the authors concluded.