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 - 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.
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U2 - 10.1158/1078-0432.CCR-19-1997
DO - 10.1158/1078-0432.CCR-19-1997
M3 - Article
C2 - 32299820
AN - SCOPUS:85089129438
SN - 1078-0432
VL - 26
SP - 3969
EP - 3978
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -