Long-term follow-up of salvage therapy using a combination of inotuzumab ozogamicin and mini–hyper-CVD with or without blinatumomab in relapsed/refractory Philadelphia chromosome–negative acute lymphoblastic leukemia

Elias Jabbour, Koji Sasaki, Nicholas J. Short, Farhad Ravandi, Xuelin Huang, Joseph D. Khoury, Rashmi Kanagal-Shamanna, Jeffrey Jorgensen, Issa F. Khouri, Partow Kebriaei, Nitin Jain, Yesid Alvarado, Tapan M. Kadia, Shilpa Paul, Guillermo Garcia-Manero, Bouthaina S. Dabaja, Jan A. Burger, Courtney D. DiNardo, Naval A. Daver, Guillermo Montalban-BravoMusa Yilmaz, Maro Ohanian, Alessandra Ferrajoli, Jovitta Jacob, Meagan Rostykus, Rebecca Garris, Susan O’Brien, Hagop M. Kantarjian

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

BACKGROUND: The outcome of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. The combination of inotuzumab with low-intensity mini–hyper-CVD (mini-hyper-CVD; cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 × 4 doses) chemotherapy has shown encouraging results. The sequential addition of blinatumomab might improve outcome in patients with R/R ALL. METHODS: We used lower intensity chemotherapy, mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses) compared to conventional hyper-CVAD. RESULTS: Ninety-six patients with a median age of 37 years (range, 18-87 years) were treated. Overall, 77 patients (80%) responded, 55 (57%) of whom achieved complete response. The overall measurable residual disease negativity rate among responders was 83%. Forty-four (46%) patients underwent later allogeneic stem cell transplantation. Veno-occlusive disease of any grade occurred in 10 (10%) patients. The rates were 13% with the original schedule and 3% with the use of lower-dose inotuzumab and sequential blinatumomab. With a median follow-up of 36 months, the median overall survival (OS) was 13.4 months, with 3-year OS rates of 33%. The 3-year OS rate for patients with CD22 expression ≥70% and without adverse cytogenetics (KMT2A rearrangements, low hypodiploidy/near triploidy) was 55%. CONCLUSION: The combination of inotuzumab and low-intensity mini-hyper-CVD chemotherapy with or without blinatumomab shows sustained efficacy in patients with R/R ALL.

Original languageEnglish (US)
Pages (from-to)2025-2038
Number of pages14
JournalCancer
Volume127
Issue number12
DOIs
StatePublished - Jun 15 2021
Externally publishedYes

Keywords

  • Philadelphia-negative ALL
  • blinatumomab
  • chemo-immunotherapy
  • inotuzumab
  • outcome
  • salvage

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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