Results of Salvage Therapy With Mini-Hyper-Cvd and Inotuzumab Ozogamicin With or Without Blinatumomab in Pre-B Acute Lymphoblastic Leukemia

Authors

Hagop Kantarjian
Fadi G Haddad
Nitin Jain
Koji Sasaki
Nicholas J Short
Sanam Loghavi
Rashmi Kanagal-Shamanna
Jeffrey Jorgensen
Issa Khouri
Partow Kebriaei
Yesid Alvarado
Tapan Kadia
Shilpa Paul
Guillermo Garcia-Manero
Bouthaina Dabaja
Musa Yilmaz
Jovitta Jacob
Rebecca Garris
Susan O'Brien
Farhad Ravandi
Elias Jabbour

Publication Date

5-2-2023

Journal

Journal of Hematology & Oncology

Abstract

Background: Historically, adults with relapsed-refractory acute lymphoblastic leukemia (ALL) experienced poor outcomes with intensive chemotherapy. This mature analysis explores the benefit of the addition of sequential blinatumomab to low-intensity mini-Hyper-CVD chemotherapy with inotuzumab ozogamicin in this setting.

Methods: Mini-Hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 83% dose reduction) was combined with inotuzumab during the first 4 courses. From Patient #68 and onwards, inotuzumab was given in reduced and fractionated doses, and blinatumomab was added sequentially for 4 courses. Maintenance therapy with prednisone, vincristine, 6-mercaptopurine and methotrexate was given for 12 courses, and blinatumomab for 4 additional courses.

Results: Among 110 patients (median age, 37 years) treated, 91 (83%) responded (complete response, 69 patients, 63%). Measurable residual disease negativity was documented in 75 patients (82% of responders). Fifty-three patients (48%) received allogeneic stem cell transplantation (SCT). Hepatic sinusoidal obstruction syndrome occurred in 9/67 patients (13%) on the original inotuzumab schedule and in 1/43 (2%) on the modified schedule. With a median follow-up of 48 months, the median overall survival (OS) was 17 months, and the 3 year OS was 40%. The 3 year OS was 34% with mini-Hyper-CVD plus inotuzumab and 52% with additional blinatumomab (P = 0.16). By landmark analysis at 4 months, the 3 year OS was 54%, similar between patients who did or did not receive allogeneic SCT.

Conclusion: Low-intensity mini-Hyper-CVD plus inotuzumab with or without blinatumomab showed efficacy in patients with relapsed-refractory ALL, with better survival after the addition of blinatumomab. Trial registration The trial was registered on clinicaltrials.gov with the identifier NCT01371630.

Keywords

Adult, Humans, Antibodies, Bispecific, Cardiovascular Diseases, Inotuzumab Ozogamicin, Methotrexate, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Salvage Therapy, Philadelphia-negative ALL, Inotuzumab, Blinatumomab, Chemo-immunotherapy, Salvage, Outcome

DOI

10.1186/s13045-023-01444-2

PMID

37131217

PMCID

PMC10155451

PubMedCentral® Posted Date

5-2-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes