TY - JOUR
T1 - A Multicenter Phase II, Double-Blind, Placebo-Controlled Trial of Maintenance Ixazomib After Allogeneic Transplantation for High-Risk Multiple Myeloma
T2 - Results of the Blood and Marrow Transplant Clinical Trials Network 1302 Trial
AU - Bashir, Qaiser
AU - Nishihori, Taiga
AU - Pasquini, Marcelo C.
AU - Martens, Michael J.
AU - Wu, Juan
AU - Alsina, Melissa
AU - Anasetti, Claudio
AU - Brunstein, Claudio
AU - Dawson, Peter
AU - Efebera, Yvonne
AU - Gasparetto, Cristina
AU - Geller, Nancy
AU - Giralt, Sergio
AU - Hall, Aric C.
AU - Koreth, John
AU - McCarthy, Philip
AU - Scott, Emma
AU - Stadtmauer, Edward A.
AU - Vesole, David H.
AU - Hari, Parameswaran
N1 - Publisher Copyright:
© 2023
PY - 2023/6
Y1 - 2023/6
N2 - The role of allogeneic hematopoietic cell transplantation (allo-HCT) followed by maintenance therapy in high-risk multiple myeloma (MM) remains controversial. We evaluated the efficacy of ixazomib maintenance therapy after reduced-intensity conditioning allo-HCT from HLA-matched donors in patients with high-risk MM. The primary study endpoint was progression-free survival (PFS) postrandomization, treated as a time to event. Secondary endpoints were grade II-IV and grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, best response, disease progression, nonrelapse mortality (NRM), overall survival (OS), toxicity, infection, and health-related quality of life. In this phase 2, double-blinded, prospective multicenter trial, we randomized patients with high-risk MM (ie, those with poor-risk cytogenetics, plasma cell leukemia, or relapsing within 24 months after autologous HCT) to ixazomib (3 mg on days 1, 8, and 15) or placebo after allo-HCT. The conditioning regimen included fludarabine/melphalan/bortezomib with tacrolimus plus methotrexate for GVHD. Fifty-seven patients were enrolled, of whom 52 (91.2%) underwent allo-HCT and 43 (82.7%) were randomized to ixazomib versus placebo. At 21 months postrandomization, the ixazomib and placebo groups had similar PFS (55.3% versus 59.1%; P = 1.00) and OS (94.7% versus 86.4%; P = .17). The cumulative incidences of grade III-IV acute GVHD at 100 days (9.5% versus 0%) and chronic GVHD at 12 months (68.6% versus 63.6%) also were similar in the 2 groups. The secondary analysis showed that at 24 months post-allo-HCT, PFS and OS were 52% and 82%, respectively, with a corresponding NRM of 11.7%. These results demonstrate the safety and durable disease control with allo-HCT in high-risk MM patients. We could not adequately assess the efficacy of ixazomib maintenance because the trial terminated early owing to enrollment delays, but there was no indication of any impact on outcomes.
AB - The role of allogeneic hematopoietic cell transplantation (allo-HCT) followed by maintenance therapy in high-risk multiple myeloma (MM) remains controversial. We evaluated the efficacy of ixazomib maintenance therapy after reduced-intensity conditioning allo-HCT from HLA-matched donors in patients with high-risk MM. The primary study endpoint was progression-free survival (PFS) postrandomization, treated as a time to event. Secondary endpoints were grade II-IV and grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, best response, disease progression, nonrelapse mortality (NRM), overall survival (OS), toxicity, infection, and health-related quality of life. In this phase 2, double-blinded, prospective multicenter trial, we randomized patients with high-risk MM (ie, those with poor-risk cytogenetics, plasma cell leukemia, or relapsing within 24 months after autologous HCT) to ixazomib (3 mg on days 1, 8, and 15) or placebo after allo-HCT. The conditioning regimen included fludarabine/melphalan/bortezomib with tacrolimus plus methotrexate for GVHD. Fifty-seven patients were enrolled, of whom 52 (91.2%) underwent allo-HCT and 43 (82.7%) were randomized to ixazomib versus placebo. At 21 months postrandomization, the ixazomib and placebo groups had similar PFS (55.3% versus 59.1%; P = 1.00) and OS (94.7% versus 86.4%; P = .17). The cumulative incidences of grade III-IV acute GVHD at 100 days (9.5% versus 0%) and chronic GVHD at 12 months (68.6% versus 63.6%) also were similar in the 2 groups. The secondary analysis showed that at 24 months post-allo-HCT, PFS and OS were 52% and 82%, respectively, with a corresponding NRM of 11.7%. These results demonstrate the safety and durable disease control with allo-HCT in high-risk MM patients. We could not adequately assess the efficacy of ixazomib maintenance because the trial terminated early owing to enrollment delays, but there was no indication of any impact on outcomes.
KW - Allogeneic hematopoietic cell transplantation
KW - Ixazomib
KW - Maintenance
KW - Multiple myeloma
UR - http://www.scopus.com/inward/record.url?scp=85151326035&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85151326035&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2022.07.007
DO - 10.1016/j.jtct.2022.07.007
M3 - Article
C2 - 35840087
AN - SCOPUS:85151326035
SN - 2666-6367
VL - 29
SP - 358.e1-358.e7
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 6
ER -