Combination Therapy Shows Efficacy in Relapsed, Refractory ALL

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.

In a mature analysis of the study, the researchers “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 the researchers.

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,” they concluded.

Reference

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