Carfilzomib, thalidomide, and dexamethasone are safe and effective in relapsed and/or refractory multiple myeloma: final report of the single-arm, multicenter, phase II ALLG MM018/AMN002 study

Ninkovic, S; Harrison, SJ; Lee, JJ; Murphy, N; Lee, JH; Estell, J; Chen, VM; Horvath, N; Kim, K; Eek, R; Augustson, B; Bang, SM; Huang, SY; Rajagopal, R; Szabo, F; Engeler, D; Butcher, BE; Mollee, P; Durie, B; Chng, WJ; Quach, H

Author(s): Ninkovic, S; Harrison, SJ; Lee, JJ; Murphy, N; Lee, JH; Estell, J; Chen, VM; Horvath, N; Kim, K; Eek, R; Augustson, B; Bang, SM; Huang, SY; Rajagopal, R; Szabo, F; Engeler, D; Butcher, BE; Mollee, P; Durie, B; Chng, WJ; Quach, H;
Details: Publication Year 2024-07-01,Volume 109,Issue #7,Page 2229-2238
Journal Title: Haematologica
Publication Type: Research article
Abstract: This multicenter, phase II study of the Australasian Lymphoma and Leukemia Group and the Asian Myeloma Network investigated fixed-duration (18-month) treatment with carfilzomib (K), thalidomide (T), and dexamethasone (d) (KTd) in patients with relapsed and/or refractory multiple myeloma who had received one to three prior lines of therapy. Patients received induction with up to 12 28-day cycles of carfilzomib (20 mg/m2 intravenously in cycle 1 on days 1 and 2, then 56 mg/m2 [36 mg/m2 for patients ≥75 years] from day 8 onwards), thalidomide 100 mg orally in the evening and weekly dexamethasone 40 mg (20 mg for patients ≥75 years). During maintenance, thalidomide was omitted, while carfilzomib was continued on days 1, 2, 15, and 16 with fortnightly dexamethasone. The primary endpoint was progression-free survival. Secondary endpoints were overall response rate, overall survival, duration of response, safety, and tolerability. Ninety-three patients (median age 66.3 years [range, 41.9-84.5]) were enrolled and followed up for a median of 26.4 months (range, 1.6-54.6). The median progression-free survival was 22.3 months (95% confidence interval: 15.7-25.6) and the 2-year progression-free survival was 46.3% (95% confidence interval: 35.1-52.8). The median overall survival was not reached and the 2-year overall survival was 73.8% (95% confidence interval: 62.9-81.9). The overall response rate was 88% (73% had a very good partial response or better). There was no difference in the depth of response, progression-free survival or overall survival comparing Asian and non-Asian cohorts (P=0.61). The safety profile of KTd was consistent with that of each individual drug. KTd is well tolerated and effective in patients with relapsed and/or refractory multiple myeloma irrespective of Asian or non-Asian ethnicity and provides an alternative treatment option, particularly in circumstances in which the use of carfilzomib, lenalidomide, and dexamethasone (KRd) is limited by access, cost, or renal impairment.
Publisher: Ferrata-Storti Foundation
Keywords: Humans; *Multiple Myeloma/drug therapy/mortality; *Dexamethasone/administration & dosage/therapeutic use/adverse effects; Aged; *Oligopeptides/administration & dosage/therapeutic use/adverse effects; Female; Middle Aged; Male; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects; *Thalidomide/administration & dosage/therapeutic use; Aged, 80 and over; Adult; Treatment Outcome; Drug Resistance, Neoplasm/drug effects; Recurrence
Department(s): Clinical Haematology
Publisher's Version: https://doi.org/10.3324/haematol.2023.284238
Open Access at Publisher's Site: https://doi.org/10.3324/haematol.2023.284238
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-08-06 08:24:25

Last Modified: 2024-08-06 08:24:44