Carfilzomib-Based Combination Results in Sustained MRD-Negative Complete Response in Multiple Myeloma

Upfront treatment with carfilzomib, lenalidomide, and dexamethasone with lenalidomide maintenance (KRd-r) incorporating a “by-default-delayed” autologous stem cell transplant (ASCT) strategy in newly diagnosed multiple myeloma has demonstrated high rates of minimal residual disease negativity (MRD_neg) complete response (CR).

Expanding on these results, researchers at the 60th American Society of Hematology Annual Meeting & Exposition, held December 1-4 in San Diego, California, presented long-term study results showing that these responses were sustained with a median duration of over 4 years among treatment-naïve patients with multiple myeloma.

The 45 patients in the phase 2 study were treated for 8 cycles (28-day cycles) with carfilzomib 20/36 mg/m² intravenously on days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg orally days 1-21; and dexamethasone 20/10 mg intravenously/orally days 1, 2, 8, 9, 15, 16, 22, and 23. Patients who were transplant-eligible underwent stem cell collection after 4 or more cycles and then continued KRd treatment.

Following 8 cycles of KRd, patients received 2 years of lenalidomide 10 mg oral maintenance on days 1-21.

The primary objective of the study was to assess the rate of grade ≥3 peripheral neuropathy with secondary objectives of overall response rate (ORR), MRD_neg CR, time to progression, and response duration assessed after every cycle during induction and subsequently after every 90 days of maintenance therapy. MRD_neg CR was assessed by multi-color flow cytometry after 8 cycles of induction, 1 and 2 years of lenalidomide, and then annually.

Median potential follow-up was 5.7 years. The ORR was 97.8% (95% CI, 88.2%-99.9%) with a median duration of response of 65.7 months (95% CI, 55.6-not reached months). Notably, 28 patients (62.2%) had deep responses of MRD_neg CR, and the durability of MRD_neg CR was observed up to at least 70 months with a median duration of over 4 years.

Median time to progression was over 5.5 years and median overall survival was not reached. However, at 80 months, 84.3% of patients were still alive. “As expected, patients who attained MRD_neg CR by cycle 8 had a 78% reduction in the risk of progression,” wrote the researchers.

They added that these deep responses of MRD_neg CR and long progression-free durations occurred regardless of age or cytogenic-based risk profile. Toxicities were generally manageable with no grade ≥3 neuropathy or death due to toxicity.

Reference:

Kazandijan D, Korde N, Mailankody S, et al. A phase 2 study of carfilzomib, lenalidomide, and dexamethasone with lenalidomide maitenance (KRd-r) in newly diagnosed multiple myeloma (NDMM): sustained long term deep remissions and prolonged progresion-free duration regardless of age or cytogenetic risk after 5 years of follow up. In: Proceedings from the American Society of Hematology; December 1-4, 2018; San Diego, CA. Abstract 1957.