The following is a summary of “Mini-Hyper-CVD & Inotuzumab Ozogamicin: Old Patients with B-Cell Acute Leukemia,” published in the June 2023 issue of Hematology by Jabbour, et al.

Due to the adverse disease biology and their incapacity to tolerate intensive therapy, the prognosis of older patients with B-cell acute lymphocytic leukemia is worse than that of younger patients. In these patients, the researchers intended to examine the long-term effects of inotuzumab ozogamicin with or without blinatumomab in combination with low-intensity chemotherapy. Eligible for this phase 2 open-label trial were patients aged 60 or older with newly diagnosed, Philadelphia-chromosome-negative, B-cell acute lymphocytic leukemia and an ECOG performance status of 3 or less. This research was conducted at the MD Anderson Cancer Center of the University of Texas. The induction chemotherapy consisted of mini-hyper-CVD and has previously been published; inotuzumab ozogamicin was administered intravenously on day 3 of the first four cycles at a dose of 1·3–1·8 mg/m² in cycle 1, and 1·0–1·3 mg/m² in subsequent cycles (cycles 2–4). About 3 years of dose-reduced POMP (6-mercaptopurine, vincristine, methotrexate, and prednisone) maintenance therapy was administered. 

From patient 50 onwards, the study protocol was amended to fractionate inotuzumab ozogamicin to a maximum cumulative dose of 2·7 mg/m² (0·9 mg/m² during cycle 1 fractionated into 0·6 mg/m² on day 2 and 0·3 mg/m² on day 8 of cycle 1, and 0·6 mg/m² in cycles 2–4 fractionated into 0·3 mg/m² on day 2 and 0·3 mg/m² on day 8) followed by blinatumomab for 4 cycles (cycles 5–8). Maintenance of POMP was reduced to 12 cycles, with one cycle of blinatumomab administered after every three cycles of POMP. The primary outcome was progression-free survival, and the analysis was based on the intention to treat. The current data are from the newly diagnosed, older subgroup of patients treated in the phase 2 portion of this trial; enrollment is ongoing. Between November 11, 2011, and March 31, 2022, 80 patients were enrolled and treated (32 female and 48 male patients; the median age of 68 years [IQR 63–70]), 31 of whom were treated after the protocol amendment. With a median follow-up of 928 months (IQR 42·0–106·7), progression-free survival at two years was 58·2% (95% CI 46·7–68·2), and progression-free survival at five years was 44·0% (31·2–54·3%).

At a median follow-up of 104·4 months (IQR 928–1104) for patients treated before the protocol amendment and 29·7 months (128–596) for those treated after the protocol amendment, progression-free survival did not significantly differ between the two groups (34·7 months [95% CI 15·0–68·3] vs. 56·4 months [11·3–69·7]; p=0·77). In 62 (78%) thrombocytopenia and 26 (32%) patients, febrile neutropenia was the most frequent grade 3–4 adverse event. Six patients (8%) were diagnosed with hepatic sinusoidal obstruction syndrome. There were eight (10%) fatalities attributable to infectious complications, nine (11%) deaths attributable to complications associated with secondary myeloid malignancy, and four (5%) deaths attributable to sinusoidal obstruction syndrome. In terms of progression-free survival, adding inotuzumab ozogamicin with or without blinatumomab to low-intensity chemotherapy showed promise in elderly patients with B-cell acute lymphocytic leukemia. In older patients, further attenuation of the chemotherapy regimen may enhance tolerability while maintaining efficacy.

Source: sciencedirect.com/science/article/abs/pii/S235230262300073X