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

Elias Jabbour, Koji Sasaki, Farhad Ravandi, Xuelin Huang, Nicholas J. Short, Maria Khouri, Partow Kebriaei, Jan Burger, Joseph Khoury, Jeffrey Jorgensen, Nitin Jain, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Jorge Cortes, Jovitta Jacob, Kathryn Montalbano, Rebecca Garris, Susan O’Brien, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4044-4055
Number of pages12
JournalCancer
Volume124
Issue number20
DOIs
StatePublished - Oct 15 2018
Externally publishedYes

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Stem Cell Transplantation
Drug Therapy
Vincristine
Cyclophosphamide
Dexamethasone
Disease-Free Survival
Inotuzumab Ozogamicin
blinatumomab
Recurrence
Propensity Score
Residual Neoplasm
Doxorubicin
Survival Rate
Survival

Keywords

  • acute lymphoblastic leukemia (ALL)
  • first relapse
  • inotuzumab ozogamicin
  • salvage

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Jabbour, Elias; Sasaki, Koji; Ravandi, Farhad; Huang, Xuelin; Short, Nicholas J.; Khouri, Maria; Kebriaei, Partow; Burger, Jan; Khoury, Joseph; Jorgensen, Jeffrey; Jain, Nitin; Konopleva, Marina; Garcia-Manero, Guillermo; Kadia, Tapan; Cortes, Jorge; Jacob, Jovitta; Montalbano, Kathryn; Garris, Rebecca; O’Brien, Susan; Kantarjian, Hagop M.

In: Cancer, Vol. 124, No. 20, 15.10.2018, p. 4044-4055.

Research output: Contribution to journalArticle

Jabbour, E, Sasaki, K, Ravandi, F, Huang, X, Short, NJ, Khouri, M, Kebriaei, P, Burger, J, Khoury, J, Jorgensen, J, Jain, N, Konopleva, M, Garcia-Manero, G, Kadia, T, Cortes, J, Jacob, J, Montalbano, K, Garris, R, O’Brien, S & Kantarjian, HM 2018, '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', Cancer, vol. 124, no. 20, pp. 4044-4055. https://doi.org/10.1002/cncr.31720
Jabbour, Elias ; Sasaki, Koji ; Ravandi, Farhad ; Huang, Xuelin ; Short, Nicholas J. ; Khouri, Maria ; Kebriaei, Partow ; Burger, Jan ; Khoury, Joseph ; Jorgensen, Jeffrey ; Jain, Nitin ; Konopleva, Marina ; Garcia-Manero, Guillermo ; Kadia, Tapan ; Cortes, Jorge ; Jacob, Jovitta ; Montalbano, Kathryn ; Garris, Rebecca ; O’Brien, Susan ; Kantarjian, Hagop M. / 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. In: Cancer. 2018 ; Vol. 124, No. 20. pp. 4044-4055.
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abstract = "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.",
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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.

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

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C2 - 30307611

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VL - 124

SP - 4044

EP - 4055

JO - Cancer

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