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

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Researchers at the 60th American Society of Hematology Annual Meeting & Exposition presented long-term study results showing that high rates of minimal residual disease–negative complete response were sustained with a median duration of over 4 years among treatment-naïve patients with 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 (MRDneg) 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), MRDneg CR, time to progression, and response duration assessed after every cycle during induction and subsequently after every 90 days of maintenance therapy. MRDneg 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 MRDneg CR, and the durability of MRDneg 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 MRDneg CR by cycle 8 had a 78% reduction in the risk of progression,” wrote the researchers.

They added that these deep responses of MRDneg 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.

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