TY - JOUR
T1 - Differential impact of minimal residual disease negativity according to the salvage status in patients with relapsed/refractory B-cell acute lymphoblastic leukemia
AU - Jabbour, Elias
AU - Short, Nicholas J.
AU - Jorgensen, Jeffrey L.
AU - Yilmaz, Musa
AU - Ravandi, Farhad
AU - Wang, Sa A.
AU - Thomas, Deborah A.
AU - Khoury, Joseph
AU - Champlin, Richard E.
AU - Khouri, Issa
AU - Kebriaei, Partow
AU - O'Brien, Susan M.
AU - Garcia-Manero, Guillermo
AU - Cortes, Jorge E.
AU - Sasaki, Koji
AU - Dinardo, Courtney D.
AU - Kadia, Tapan M.
AU - Jain, Nitin
AU - Konopleva, Marina
AU - Garris, Rebecca
AU - Kantarjian, Hagop M.
N1 - Publisher Copyright:
© 2016 American Cancer Society
PY - 2017/1/1
Y1 - 2017/1/1
N2 - BACKGROUND: Minimal residual disease (MRD) assessment predicts survival for patients with newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear. METHODS: This study identified 78 patients with relapsed/refractory B-cell ALL who achieved a morphologic response with inotuzumab ozogamicin (n = 41), blinatumomab (n = 11), or mini-hyperfractionated cyclophosphamide, vincristine, and doxorubicin plus inotuzumab (n = 26) during either salvage 1 (S1; n = 46) or salvage 2 (S2; n = 32) and had undergone an MRD assessment by multiparameter flow cytometry at the time of remission. RESULTS: MRD negativity was achieved in 41 patients overall (53%). The MRD negativity rate was 57% in S1 and 47% in S2. Among patients in S1, achieving MRD negativity was associated with longer event-free survival (EFS; median, 18 vs 7 months; 2-year EFS rate, 46% vs 17%; P =.06) and overall survival (OS; median, 27 vs 9 months; 2-year OS, 52% vs 36%; P =.15). EFS and OS were similar in S2, regardless of the MRD response. Among MRD-negative patients who underwent allogeneic stem cell transplantation (SCT), EFS and OS were superior for those who underwent SCT in S1 rather than S2 (P =.003 and P =.04, respectively). Patients in S1 who achieved MRD negativity and subsequently underwent SCT had the best outcomes with a 2-year OS rate of 65%. CONCLUSIONS: Patients with relapsed/refractory ALL who achieve MRD negativity in S1 can have long-term survival. Patients in S2 generally have poor outcomes, regardless of their MRD status. Cancer 2017;123:294–302.
AB - BACKGROUND: Minimal residual disease (MRD) assessment predicts survival for patients with newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear. METHODS: This study identified 78 patients with relapsed/refractory B-cell ALL who achieved a morphologic response with inotuzumab ozogamicin (n = 41), blinatumomab (n = 11), or mini-hyperfractionated cyclophosphamide, vincristine, and doxorubicin plus inotuzumab (n = 26) during either salvage 1 (S1; n = 46) or salvage 2 (S2; n = 32) and had undergone an MRD assessment by multiparameter flow cytometry at the time of remission. RESULTS: MRD negativity was achieved in 41 patients overall (53%). The MRD negativity rate was 57% in S1 and 47% in S2. Among patients in S1, achieving MRD negativity was associated with longer event-free survival (EFS; median, 18 vs 7 months; 2-year EFS rate, 46% vs 17%; P =.06) and overall survival (OS; median, 27 vs 9 months; 2-year OS, 52% vs 36%; P =.15). EFS and OS were similar in S2, regardless of the MRD response. Among MRD-negative patients who underwent allogeneic stem cell transplantation (SCT), EFS and OS were superior for those who underwent SCT in S1 rather than S2 (P =.003 and P =.04, respectively). Patients in S1 who achieved MRD negativity and subsequently underwent SCT had the best outcomes with a 2-year OS rate of 65%. CONCLUSIONS: Patients with relapsed/refractory ALL who achieve MRD negativity in S1 can have long-term survival. Patients in S2 generally have poor outcomes, regardless of their MRD status. Cancer 2017;123:294–302.
KW - acute lymphoblastic leukemia
KW - blinatumomab
KW - inotuzumab
KW - minimal residual disease
KW - refractory
KW - relapsed
UR - http://www.scopus.com/inward/record.url?scp=84992535694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992535694&partnerID=8YFLogxK
U2 - 10.1002/cncr.30264
DO - 10.1002/cncr.30264
M3 - Article
C2 - 27602508
AN - SCOPUS:84992535694
SN - 0008-543X
VL - 123
SP - 294
EP - 302
JO - Cancer
JF - Cancer
IS - 2
ER -