TY - JOUR
T1 - Chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD, with or without blinatumomab, is highly effective in patients with Philadelphia chromosome–negative acute lymphoblastic leukemia in first salvage
AU - Jabbour, Elias
AU - Sasaki, Koji
AU - Ravandi, Farhad
AU - Huang, Xuelin
AU - Short, Nicholas J.
AU - Khouri, Maria
AU - Kebriaei, Partow
AU - Burger, Jan
AU - Khoury, Joseph
AU - Jorgensen, Jeffrey
AU - Jain, Nitin
AU - Konopleva, Marina
AU - Garcia-Manero, Guillermo
AU - Kadia, Tapan
AU - Cortes, Jorge
AU - Jacob, Jovitta
AU - Montalbano, Kathryn
AU - Garris, Rebecca
AU - O’Brien, Susan
AU - Kantarjian, Hagop M.
N1 - Publisher Copyright:
© 2018 American Cancer Society
PY - 2018/10/15
Y1 - 2018/10/15
N2 - Background: The outcomes of patients with relapsed or refractory (R-R) acute lymphoblastic leukemia (ALL) are poor. Inotuzumab ozogamicin and blinatumomab have single-agent activity in R-R ALL. Their addition to low-intensity chemotherapy may further improve the outcomes of patients with ALL in their first relapse. Methods: The chemotherapy was lower in intensity than conventional hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone and was called mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone (or mini-HCVD). Inotuzumab was given on day 3 of each of the first 4 cycles at 1.8 to 1.3 mg/m2 for cycle 1, and this was followed by 1.3 to 1.0 mg/m2 for subsequent cycles. From patient 39 onward, the inotuzumab dose was reduced and fractionated into weekly doses (0.6 and 0.3 mg/m2 during cycle 1 and 0.3 and 0.3 mg/m2 during subsequent cycles), and blinatumomab was administered for up to 4 cycles after inotuzumab therapy. Results: Forty-eight patients with Philadelphia chromosome–negative ALL with a median age of 39 years were treated during their first relapse. Overall, 44 patients (92%) responded, with 35 of them (73%) achieving a complete response. The overall minimal residual disease negativity rate among the responders was 93%. Twenty-four patients (50%) underwent allogeneic stem cell transplantation (ASCT). Veno-occlusive disease of any grade occurred in 5 patients (10%). With a median follow-up of 31 months, the median progression-free survival (PFS) and the median overall survival (OS) were 11 and 25 months, respectively. The 2-year PFS and OS rates were 42% and 54%, respectively. Of the 24 patients (50%) who underwent ASCT, 14 patients were alive at the last follow-up (13 [54%] in remission). Of the remaining 20 responding patients who did not undergo subsequent ASCT, 6 (30%) remained in remission at the last follow-up. According to propensity score matching, the combination of mini-HCVD and inotuzumab with or without blinatumomab conferred better outcomes than intensive salvage chemotherapy or inotuzumab alone. Conclusions: The combination of inotuzumab and low-intensity mini-HCVD chemotherapy with or without blinatumomab shows encouraging results in patients with ALL in first salvage.
AB - Background: The outcomes of patients with relapsed or refractory (R-R) acute lymphoblastic leukemia (ALL) are poor. Inotuzumab ozogamicin and blinatumomab have single-agent activity in R-R ALL. Their addition to low-intensity chemotherapy may further improve the outcomes of patients with ALL in their first relapse. Methods: The chemotherapy was lower in intensity than conventional hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone and was called mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone (or mini-HCVD). Inotuzumab was given on day 3 of each of the first 4 cycles at 1.8 to 1.3 mg/m2 for cycle 1, and this was followed by 1.3 to 1.0 mg/m2 for subsequent cycles. From patient 39 onward, the inotuzumab dose was reduced and fractionated into weekly doses (0.6 and 0.3 mg/m2 during cycle 1 and 0.3 and 0.3 mg/m2 during subsequent cycles), and blinatumomab was administered for up to 4 cycles after inotuzumab therapy. Results: Forty-eight patients with Philadelphia chromosome–negative ALL with a median age of 39 years were treated during their first relapse. Overall, 44 patients (92%) responded, with 35 of them (73%) achieving a complete response. The overall minimal residual disease negativity rate among the responders was 93%. Twenty-four patients (50%) underwent allogeneic stem cell transplantation (ASCT). Veno-occlusive disease of any grade occurred in 5 patients (10%). With a median follow-up of 31 months, the median progression-free survival (PFS) and the median overall survival (OS) were 11 and 25 months, respectively. The 2-year PFS and OS rates were 42% and 54%, respectively. Of the 24 patients (50%) who underwent ASCT, 14 patients were alive at the last follow-up (13 [54%] in remission). Of the remaining 20 responding patients who did not undergo subsequent ASCT, 6 (30%) remained in remission at the last follow-up. According to propensity score matching, the combination of mini-HCVD and inotuzumab with or without blinatumomab conferred better outcomes than intensive salvage chemotherapy or inotuzumab alone. Conclusions: The combination of inotuzumab and low-intensity mini-HCVD chemotherapy with or without blinatumomab shows encouraging results in patients with ALL in first salvage.
KW - acute lymphoblastic leukemia (ALL)
KW - first relapse
KW - inotuzumab ozogamicin
KW - salvage
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U2 - 10.1002/cncr.31720
DO - 10.1002/cncr.31720
M3 - Article
C2 - 30307611
AN - SCOPUS:85054769674
SN - 0008-543X
VL - 124
SP - 4044
EP - 4055
JO - Cancer
JF - Cancer
IS - 20
ER -
