Mini-Hyper CVD Chemotherapy Plus Inotuzumab Ozogamicin Regimen With or Without Blinatumomab Demonstrates Efficacy, Safety for R/R Pre-B ALL

A treatment regimen of low-intensity mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 83% dose reduction) plus inotuzumab with or without blinatumomab showed efficacy among patients with relapsed/refractory (R/R) Philadelphia chromosome-negative CD22-positive pre-B acute lymphoblastic leukemia (ALL), according to an updated analysis of a phase 2 trial published in the Journal of Hematology & Oncology.

Additionally, the trial demonstrated improved survival after the addition of blinatumomab. These results indicate that the addition of blinatumomab to this regimen has potential to improve patient outcomes.

Hagop Kantarjian, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, and coauthors wrote, “In this updated analysis with a median follow-up of 48 months, we report the long‐term results of this regimen (mini-Hyper-CVD-inotuzumab ± blinatumomab) in 110 patients, and assess the impact of reducing and fractionating inotuzumab, and of adding sequential blinatumomab, on the long-term outcome of patients with R/R ALL.”

In this study, the mini-hyper-CVD regimen was combined with inotuzumab during the first 4 courses. In an amendment of the study protocol to reduce the risk of hepatic sinusoidal obstruction syndrome (SOS) and improve outcomes, 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.

Among 110 patients with a median age of 37 years who were treated, 91 (83%) responded (complete response, 69 patients, 63%). Measurable residual disease negativity was documented in 75 patients (82% of responders). The study noted that 53 of the patients (48%) received allogeneic stem cell transplantation (SCT). Hepatic sinusoidal obstruction syndrome occurred in 9 out of 67 patients (13%) on the original inotuzumab schedule, and in 1 out of 43 (2%) on the modified schedule. 

At the 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%, which was similar between patients who did or did not receive allogeneic SCT.

All 110 patients were evaluable for safety analyses. As for adverse events, the treatment was well-tolerated with most side effects being grade 1 to 2. Early mortality was noted in 6% of patients, notably, all of them treated before the amendment of the protocol. 9 patients died in complete remission (CR), with 2 of infections, 1 of myocardial infarction, 1 of bronchopulmonary hemorrhage, 1 of graft-versus-host disease. In 4 patients the cause of death was unknown. Of the 30 patients who received blinatumomab, no patients discontinued blinatumomab due to blinatumomab-related adverse events.

Dr Kantarjian and coauthors concluded, “The long-term follow-up of the mini-hyper-CVD-inotuzumab ± blinatumomab confirmed the efficacy and safety of this regimen, and showed that the addition of blinatumomab may further improve outcomes.” 

“Confirmation in a large multi-institutional trial is needed in order to establish it as a new form of standard of care therapy in adult R/R ALL,” they added. 

Source: 

Kantarjian, H., Haddad, F.G., 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. May 2, 2023; 16 (44) doi:10.1186/s13045-023-01444-2