TY - JOUR
T1 - Low-dose versus High-dose Carfilzomib with Dexamethasone (S1304) in Patients with Relapsed-Refractory Multiple Myeloma
AU - Ailawadhi, Sikander
AU - Sexton, Rachael
AU - Lentzsch, Suzanne
AU - Abidi, Muneer H.
AU - Voorhees, Peter M.
AU - Cohen, Adam D.
AU - Rohren, Eric M.
AU - Heitner, Stephen
AU - Kelly, Kevin
AU - Mackler, Niklas J.
AU - Baer, David M.
AU - Hoering, Antje
AU - Durie, Brian
AU - Orlowski, Robert Z.
N1 - Funding Information:
This work was supported by NIH/NCI grants CA180888, CA180819, CA180820, CA180821, CA180830, CA189821, CA189971, CA180826, CA189830, CA180858, CA189858, CA189872, CA189829, CA180846, CA139519, CA189822, CA180798, CA189808, and CA189952, legacy grants CA46282 and CA13612, and in part by Onyx Pharmaceuticals, Inc. (AMGEN subsidiary). R. Z. Orlowski, the Florence Maude Thomas Cancer Research Professor, would like to acknowledge support from the National Cancer Institute (R01 CA194264, R01 CA184464), and the Leukemia & Lymphoma Society (SCOR-12206-17). Additional support came from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.
Publisher Copyright:
©2020 American Association for Cancer Research.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Purpose: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits. Patients and Methods: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m2; arm 1) to high-dose carfilzomib (56 mg/m2; arm 2), both with dexamethasone, administered for 12 cycles (11 months) for relapsed and/or refractory multiple myeloma with up to six prior lines of therapy (NCT01903811). The primary endpoint was progression-free survival (PFS), and patients on arm 1 could cross-over to arm 2 after progression on treatment. Results: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (P ¼ 0.113). Also, neither the median PFS [5 months and 8 months, respectively; HR, 1.061; 80% Wald confidence interval (CI), 0.821–1.370; P ¼ 0.384] nor the median overall survival were significantly different (26 and 22 months, respectively; HR, 1.149, 80% Wald CI, 0.841–.571; P ¼ 0.284). Sixteen patients crossed over to arm 2 with a median PFS benefit of 3 months. Certain adverse events (AE) were more frequent in arm 2, including fatigue, thrombocytopenia, and peripheral neuropathy, but there was no significant difference in cardiopulmonary AEs. Conclusions: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m2 dosing of carfilzomib over the 27 mg/m2 dose for the treatment of relapsed and/or refractory multiple myeloma. However, treatment to progression in earlier patient populations with high-dose carfilzomib using different schedules should still be considered as part of the standard of care.
AB - Purpose: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits. Patients and Methods: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m2; arm 1) to high-dose carfilzomib (56 mg/m2; arm 2), both with dexamethasone, administered for 12 cycles (11 months) for relapsed and/or refractory multiple myeloma with up to six prior lines of therapy (NCT01903811). The primary endpoint was progression-free survival (PFS), and patients on arm 1 could cross-over to arm 2 after progression on treatment. Results: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (P ¼ 0.113). Also, neither the median PFS [5 months and 8 months, respectively; HR, 1.061; 80% Wald confidence interval (CI), 0.821–1.370; P ¼ 0.384] nor the median overall survival were significantly different (26 and 22 months, respectively; HR, 1.149, 80% Wald CI, 0.841–.571; P ¼ 0.284). Sixteen patients crossed over to arm 2 with a median PFS benefit of 3 months. Certain adverse events (AE) were more frequent in arm 2, including fatigue, thrombocytopenia, and peripheral neuropathy, but there was no significant difference in cardiopulmonary AEs. Conclusions: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m2 dosing of carfilzomib over the 27 mg/m2 dose for the treatment of relapsed and/or refractory multiple myeloma. However, treatment to progression in earlier patient populations with high-dose carfilzomib using different schedules should still be considered as part of the standard of care.
UR - http://www.scopus.com/inward/record.url?scp=85089129438&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089129438&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-1997
DO - 10.1158/1078-0432.CCR-19-1997
M3 - Article
C2 - 32299820
AN - SCOPUS:85089129438
VL - 26
SP - 3969
EP - 3978
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 15
ER -