Carfilzomib Noninferior to Bortezomib as Second-Line Treatment for Multiple Myeloma

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Carfilzomib is noninferior to bortezomib as second-line treatment for relapsed or refractory multiple myeloma (MM), according to a phase 2 study published in Haematologica.

The researchers noted that head-to-head studies comparing the efficacy of carfilzomib to bortezomib have provided mixed results.

The aim of the phase 2 MUKfive trial was to compare fixed-duration carfilzomib plus cyclophosphamide and dexamethasone (KCd) with bortezomib plus cyclophosphamide and dexamethasone (VCd) and determine the efficacy and safety of carfilzomib maintenance.


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The trial enrolled 300 patients with relapsed/refractory MM who had received 1 prior therapy. Their median age at baseline was 68 years (range, 32-85 years). Most patients had a prior transplant (66.7%), 21.7% had received bortezomib, and 22.7% had received lenalidomide.   

The patients were randomly assigned to receive KCd (n=201) or VCd (n=99) for 24 weeks. Patients who responded to KCd (n=141) were then randomly assigned 1:1 to receive carfilzomib maintenance for 18 cycles or no further treatment.

The study’s co-primary endpoints were very good partial response (VGPR) at 24 weeks after initial therapy and progression-free survival (PFS) after maintenance.

KCd was noninferior to VCd after initial therapy. The VGPR rate was 40.2% with KCd and 31.9% with VCd (odds ratio [OR], 1.48; 90% CI, 0.95-2.31).

Patients with adverse-risk genetics had higher VGPR rates with KCd than with VCd — 38.2% and 21.9%, respectively (OR, 2.47; 90% CI, 1.07-5.72). However, VGPR rates were similar between the arms for patients with standard-risk genetics.

The overall response rate was significantly higher with KCd than with VCd — 84.0% and 68.1%, respectively (OR, 2.72; 90% CI, 1.62-4.55; P =.0014).

The median PFS was significantly longer with carfilzomib maintenance than without it — 11.9 months and 5.6 months, respectively (hazard ratio, 0.59; 80% CI, 0.46-0.77; P =.0086).

The incidence of neuropathy (≥ grade 3 or ≥ grade 2 with pain) was significantly higher in the VCd arm than in the KCd arm — 19.8% and 1.5%, respectively (P <.0001).

Grade 3 or higher cardiac events and hypertension events each occurred in 3.6% of patients in the KCd arm, but none were reported with VCd.

Treatment discontinuation due to toxicity occurred in 7.0% of KCd recipients and 19.2% of VCd recipients. Dose modifications were required for 82.1% of patients on carfilzomib maintenance.

Based on these results, the researchers concluded that fixed-duration KCd is “at least as effective as VCd” for treating MM in first relapse, and carfilzomib is an effective maintenance therapy in this population.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Yong KL, Hinsley S, Auner HW, et al. Carfilzomib or bortezomib in combination with cyclophosphamide and dexamethasone followed by carfilzomib maintenance for patients with multiple myeloma after one prior therapy: Results from a multicenter, phase II, randomized, controlled trial (MUKfive). Haematologica. 2021;106:2694-2706. doi:10.3324/haematol.2021.278399



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