In a single-center phase II study reported in The Lancet Oncology, Kantarjian et al found that the addition of inotuzumab ozogamicin (Besponsa) to low-intensity chemotherapy produced promising outcomes in older patients with newly diagnosed Philadelphia chromosome–negative acute lymphoblastic leukemia (ALL).
The study included 52 patients aged ≥ 60 years (median = 68 years) enrolled at MD Anderson Cancer Center between November 2011 and April 2017.
Induction chemotherapy consisted of mini–hyper-CVD: cyclophosphamide (150 mg/m² every 12 hours on days 1–3) and dexamethasone (20 mg/d on days 1–4 and days 11–14) in cycles 1, 3, 5, and 7, with no anthracycline, and vincristine (2 mg flat dose) on days 1 and 8; and methotrexate (250 mg/m² on day 1) and cytarabine (0.5 g/m² every 12 hours on days 2 and 3) in even-numbered cycles. Inotuzumab ozogamicin was given on day 3 of the first four cycles at 1.3–1.8 mg/m² in cycle 1 followed by 1.0–1.3 mg/m² in subsequent cycles. Maintenance therapy with dose-reduced POMP (6-mercaptopurine, vincristine, methotrexate, and prednisone) was given for 3 years.
Of the 52 patients, 48 were treatment-naive and 4 were enrolled after achieving complete response after one cycle of previous therapy. The primary endpoint was progression-free survival at 2 years in the intent-to-treat population. The study is ongoing and recruiting patients for an approved expansion phase with a modified treatment plan.
Median follow-up was 29 months. Estimated progression-free survival was 59% at 2 years and 49% at 3 years; median progression-free survival was 35 months. Estimated overall survival was 66% at 2 years and 56% at 3 years; median overall survival was not reached. Response was achieved in 47 (98%) of 48 previously untreated patients, with complete response in 41 (85%).
The most common grade 3 or 4 adverse events were prolonged thrombocytopenia (81%), infection during induction (52%) and consolidation chemotherapy (69%), hyperglycemia (54%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Veno-occlusive disease occurred in 8%. Six (12%) patients died from adverse events considered related to treatment, including five from sepsis and one from veno-occlusive disease.
The investigators concluded, “Inotuzumab ozogamicin plus mini–hyper-CVD chemotherapy is a safe and active first-line therapy option in older patients with newly diagnosed acute lymphoblastic leukaemia and could represent a new therapy for this population. Randomised, phase III trials to evaluate the efficacy of this combination compared with the current standard of care in this setting, combination chemotherapy without inotuzumab ozogamicin, are warranted.”
The study was funded by MD Anderson Cancer Center.
Hagop Kantarjian, MD, of the Department of Leukemia, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.
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