A phase 1/2 of carfilzomib and melphalan conditioning for autologous stem cell transplantation for multiple myeloma (CARAMEL).

Autor: Visram A; Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada., Hayman SR; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Dispenzieri A; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Kapoor P; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Lacy MQ; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Gertz MA; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Buadi FK; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Dingli D; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Warsame R; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Kourelis T; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Cook J; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Binder M; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Gonsalves W; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Muchtar E; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Leung N; Division of Nephrology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Roy V; Division of Hematology, Mayo Clinic, Jacksonville, Florida, USA., Rajkumar SV; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Kumar S; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2023 Aug; Vol. 98 (8), pp. 1277-1285. Date of Electronic Publication: 2023 Jun 19.
DOI: 10.1002/ajh.26990
Abstrakt: In this phase 1/2 study, carfilzomib was added to high-dose melphalan conditioning prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma that had been treated with ≤2 prior lines of therapy. Carfilzomib was escalated at doses of 27, 36, 45, and 56 mg/m2 on days -6, -5, -2, and -1 before ASCT in the phase 1 component of the study. In addition, all the patients received melphalan 100 mg/m 2 on days -4 and -3. The primary endpoint of the phase 1 component was to identify the maximum tolerated dose, and the primary endpoint of the phase 2 component was the rates of complete response (≥CR) at 1 year after ASCT. The phase 1 dose escalation cohort included 14 patients, and 35 patients were included in the phase 2 cohort. The maximum tested dose was 56 mg/m 2 (MTD). The median time from diagnosis to study enrollment was 5.8 (range 3.4-88.4) months, and 16% of patients had obtained a ≥CR prior to ASCT. The best response within 1 year after ASCT was a ≥ CR rate in 22% for the entire cohort, and 22% for patients treated at the MTD. The ≥VGPR rates improved from 41% before ASCT to 77% by 1 year after ASCT. One patient had a grade 3 renal adverse event, and renal function returned to baseline with supportive care. The rate of grade 3-4 cardiovascular toxicity was 16%. The addition of carfilzomib to melphalan conditioning was safe and resulted in deep responses after ASCT.
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Databáze: MEDLINE
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