Treatment with carfilzomib combination therapies are mostly feasible for patients with relapsed/refractory multiple myeloma (RRMM), but further strategies that can overcome bortezomib or lenalidomide resistance are still needed, according to research published in Cancer Reports.

Resistance to bortezomib or lenalidomide is strongly associated with failure to first-line therapy, and may have prognostic significance to response to carfilzomib-based regimens for salvage therapy.

RRMM remains an incurable disease. Combination therapies with carfilzomib plus dexamethasone with or without lenalidomide have shown promise for patients with RRMM. However, the real-world efficacy of these combinations for patients with resistance has not been evaluated.

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The multicenter, pilot, prospective observational study in Kyoto evaluated 50 Asian patients with RRMM who received carfilzomib-based treatments. A total of 31 patients received carfilzomib with dexamethasone and lenalidomide (KRD) and 19 received carfilzomib plus dexamethasone (KD) therapy.

A total of 90% of patients in the study had received prior treatment with bortezomib, and 70% had previously received lenalidomide. There were 21 patients who were refractory to bortezomib, and 19 were refractory to lenalidomide.

The overall response rate (ORR) was 78% at a median follow-up of 28.3 months, with no significant difference between therapies. The 2-year progression-free survival (PFS) was 44.4%, and the overall survival (OS) was 69.5%.

The KRD therapy group had a longer OS, with the median not reached, than the KD group, which had a median OS of 28.1 months (P =.001). Patients who were refractory to bortezomib or lenalidomide had shorter PFS and OS, with double-refractory patients having the poorest prognosis. A total of 86% of patients experienced hematological adverse events.

Overall, this real-world study found that carfilzomib-based treatment is feasible and effective in Asian patients with RRMM. However, prior resistance to bortezomib or lenalidomide may limit the efficacy of these therapies.

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


Kawaji-Kanayama Y, Kobayashi T, Muramatsu A, et al. Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib-based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients. Cancer Rep (Hoboken). 2021;e1476. doi:10.1002/cnr2.1476