Combination Therapy Shows Efficacy in Relapsed, Refractory ALL

By Cecilia Brown - May 23, 2023

Low-intensity chemotherapy plus inotuzumab showed “better survival” outcomes after the addition of blinatumomab in patients with relapsed or refractory acute lymphoblastic leukemia (ALL), according to a recent study.

Elias Jabbour, MD, of the MD Anderson Cancer Center, and colleagues conducted the study to address the “poor outcomes with intensive chemotherapy” in adults with relapsed or refractory ALL.

In a mature analysis of the study, they “explored the benefit” of adding sequential blinatumomab to low-intensity minihyper-CVD chemotherapy with inotuzumab ozogamicin in this setting. The study included 110 patients with a median age of 37 years.

During the first four courses of therapy, patients received inotuzumab with minihyper-CVD, which consisted of cyclophosphamide and dexamethasone at a 50% dose reduction, no anthracycline, methotrexate at a 75% dose reduction, and cytarabine at an 83% dose reduction. Starting with patient 68, patients received inotuzumab in reduced and fractionated doses, with blinatumomab added sequentially for four courses. Maintenance therapy consisted of 12 courses of prednisone, vincristine, 6-mercaptopurine, and methotrexate, and four additional courses of blinatumomab.

Most patients (83%) responded to the treatment, with 63% having a complete response. Among the patients who responded, 82% were negative for measurable residual disease. Around half (48%) of the patients received an allogeneic hematopoietic stem cell transplantation (HSCT).

The median overall survival (OS) was 17 months, while the three-year OS rate was 40% at a median follow-up of 48 months. The three-year OS rate was 34% in patients who received minihyper-CVD plus inotuzumab, while the three-year OS rate was 52% in those who received the treatment with additional blinatumomab (P=.16). A landmark analysis at four months showed the three-year OS was 54% and was “similar” between patients who underwent HSCT and those who did not, according to Dr. Jabbour and colleagues.

Hepatic sinusoidal obstruction syndrome occurred in nine of the 67 (13%) patients who were on the original inotuzumab schedule and in one of the 43 (2%) patients on the modified schedule.

“Low-intensity minihyper-CVD plus inotuzumab with or without blinatumomab showed efficacy in patients with relapsed [or] refractory ALL, with better survival after the addition of blinatumomab,” Dr. Jabbour and colleagues concluded.


Kantarjian H, Haddad FG, Jain N, et al. Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia. J Hematol Oncol. 2023;16(1):44. doi:10.1186/s13045-023-01444-2

Editorial Board