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.

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.

• Authors: 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-Bravo, Musa Yilmaz, Maro Ohanian, Alessandra Ferrajoli, Jovitta Jacob, Meagan Rostykus, Rebecca Garris, Susan O'Brien, Hagop M Kantarjian
• Journal: Cancer (Cancer) Vol. 127 Issue 12 Pg. 2025-2038 (06 15 2021) ISSN: 1097-0142 [Electronic] United States
• PMID: 33740268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 American Cancer Society.

Chemical References

• Antibodies, Bispecific
• blinatumomab
• Inotuzumab Ozogamicin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Bispecific
• Follow-Up Studies
• Humans
• Inotuzumab Ozogamicin
• Middle Aged
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, genetics)
• Salvage Therapy (methods)
• Young Adult