Phase II Trial Evaluates Combination Therapy in Older Adults with B-Cell ALL

Inotuzumab ozogamicin with or without blinatumomab plus low intensity chemotherapy showed “promising activity in terms of progression-free survival” (PFS) in older patients with B-cell acute lymphocytic leukemia (ALL), according to a phase II trial.

The open-label trial, led by Elias Jabbour, MD, of the MD Anderson Cancer Center, included patients who were aged 60 years or older and had newly diagnosed Philadelphia chromosome-negative B-cell ALL. The trial’s investigators enrolled and treated 80 patients between November 2011 and March 2022. The median patient age was 68 years.

Patients received induction chemotherapy with minihyper-CVD. They received inotuzumab ozogamicin intravenously on day three of the first four cycles at a dose ranging from 1.3 to 1.8 mg/m² in cycle one, followed by dose ranging from 1.0 to 1.3 mg/m² in cycles two through four.

Patients received maintenance therapy with dose-reduced 6-mercaptoprine, vincristine, methotrexate, and prednisone (POMP) for three years.

However, from patient 50 onwards, the researchers amended the study protocol to fractionate inotuzumab ozogamicin to a maximum cumulative dose of 2.7 mg/m² followed by blinatumomab for four cycles (cycles five through eight). They also shortened the POMP maintenance therapy to 12 cycles, administering one cycle of blinatumomab by continuous infusion after every three cycles of POMP. A total of 31 patients received this treatment regimen after the study protocol amendment.

The two-year PFS rate was 58.2%, while the five-year PFS rate was 44% at a median follow-up of 92.8 months. With a median follow-up of 104.4 months for patients who received treatment before the protocol amendment and a median follow-up of 29.7 months for those who received treatment after the amendment, there were no significant differences between the median PFS for the groups. The patients treated before the protocol amendment had a median PFS of 34.7 months (95% CI, 15.0-68.3), while those who received treatment after the amendment had a median PFS of 56.4 months (95% CI, 11.3-69.7; P=.77).

The most common grade 3 to 4 events were thrombocytopenia, occurring in 62 (78%) patients, febrile neutropenia, occurring in 26 (32%) patients. Hepatic sinusoidal obstruction syndrome occurred in six (8%) patients.

The study’s investigators reported eight patients (10%) died due to infectious complications, nine patients (11%) died from complications related to secondary myeloid malignancy, and four (5%) died from sinusoidal obstruction syndrome.

There were eight (10%) deaths due to infectious complications, nine (11%) from complications related to secondary myeloid malignancy, and four (5%) from sinusoidal obstruction syndrome.

“Inotuzumab ozogamicin with or without blinatumomab added to low-intensity chemotherapy showed promising activity in terms of [PFS] in older patients with B-cell [ALL],” Dr. Jabbour and colleagues concluded. “Further attenuation of the chemotherapy regimen might improve tolerability while maintaining efficacy in older patients.”

Reference

Jabbour E, Short NJ, Senapati J, et al. Mini-hyper-CVD plus inotuzumab ozogamicin, with or without blinatumomab, in the subgroup of older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: long-term results of an open-label phase 2 trial. Lancet Haematol. 2023. doi:10.1016/S2352-3026(23)00073-X