Weekly carfilzomib plus cyclophosphamide and dexamethasone (wKCd) was found to be effective among patients with relapsed/refractory multiple myeloma (MM), according to the results of a phase 2 trial published in the American Journal of Hematology.
The wKCd protocol “provides a useful regimen in the relapsed MM with a more convenient dosing schedule much more conducive to long-term therapy,” the authors wrote.
The single-arm, phase 2 trial (ClinicalTrials.gov Identifier: NCT02597062) included 75 patients with relapsed MM treated with wKCd. The primary endpoint was overall response rate after 4 treatment cycles; secondary endpoints included progression-free survival, overall survival, response depth, and toxicity.
At baseline, the median age was 66, and 63% of patients were men. High-risk cytogenetics was present among 32% of patients, and 20% were not evaluated for risk features. The majority of patients were classified as having Revised International Staging System stage 2 MM (67%), followed by 19% at stage 1, 11% at stage 3, and 1% who were not evaluable. The majority of patients had undergone prior treatment with a proteasome inhibitor and immunomodulatory agent, and 76% had undergone autologous stem cell transplantation.
After 4 cycles, the overall response rate was 84%, with a complete response rate of 29% and at least a very good partial response rate of 68%.
During median follow-up of 24.6 months, the median progression-free survival was 17.2 months and median overall survival was 27.4 months.
Among patients evaluable for cytogenetics, the ORR was higher with favorable risk features at 97% compared with 75% among patients with high-risk cytogenetics (odds ratio [OR], 11.67; 95% CI, 1.30-104.45; P =.013).
High-risk cytogenetics was also associated with shorter progression-free survival of 13.8 months compared with 21.9 months with favorable-risk cytogenetics. Median overall survival also differed, with a median of 18.4 months with high-risk cytogenetics and not yet reached with favorable cytogenetics.
The wKCd regimen was considered well tolerated, with most treatment-related adverse events reversible. The most common adverse events included anemia, neutropenia, and thrombocytopenia. The most common nonhematologic adverse events included hypertension, dyspnea, and congestive heart failure.
The authors concluded that “wKCd is a safe and effective regimen in [relapsed MM], especially for patients ineligible for lenalidomide-based therapies.”
Venner CP, LeBlanc R, Sandhu I, et al. Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: final results from the MCRN-003/MYX.1 single arm phase II trial. Am J Hematol. Published online March 1, 2021. doi:10.1002/ajh.26147