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Inotuzumab ozogamicin, low-intensity chemotherapy combination safe in older patients with leukemia
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SAN DIEGO — Elderly patients with acute lymphoblastic leukemia demonstrated safe and encouraging results in the frontline setting after receiving a combination of inotuzumab ozogamicin and low-intensity mini-hyper-CVD chemotherapy, according to study results presented at the ASH Annual Meeting and Exposition.
The combination appeared to produce better results than those achieved with the use of hyper-CVAD with or without rituximab (Rituxan; Genentech, Biogen), according to the results.
Older patients with ALL tend to have worse outcomes compared with younger patients due to poor tolerance of intensive therapy.
Previous findings of a randomized phase 3 study – simultaneously published in The New England Journal of Medicine and presented at the European Hematology Association Congress – demonstrated that patients with ALL were more likely to achieve complete remission and disease levels below the threshold for minimal residual disease with inotuzumab ozogamicin (CMC-544, Pfizer) than standard therapy.
Koji Sasaki, MD, of The University of Texas MD Anderson Cancer Center, and colleagues conducted an analysis of 42 evaluable older patients (median age, 68 years) to assess if the addition of inotuzumab ozogamicin – a humanized anti-CD22 monoclonal antibody conjugated to calicheamicin – to effective low-intensity therapy would improve outcome.
Four patients began the study in complete remission. There was a median follow-up of 24 months.
Patients aged 60 years or older with newly diagnosed B-cell ALL were eligible for chemotherapy with mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses) in combination with inotuzumab ozogamicin given on day 3 of each of the first four courses.
Rituximab – in patients whose cells were CD20 positive – and intrathecal chemotherapy were given for the first four courses. The first six patients received inotuzumab ozogamicin at 1.3 mg/m2 for cycle 1 followed by 0.8 mg/m2 for subsequent cycles. After the first six patients, the rest received 1.8 mg/m2 for the first cycle followed by 1.3 mg/m2 for subsequent cycles.
However, after the occurrence of hepatic veno-occlusive disease in four patients, researchers modified the dosing to 1.3 mg/m2 for the first cycle followed by 1.0 mg/m2 for subsequent cycles.
Thirty-five patients achieved complete response and five achieved a complete response with incomplete platelet recovery.
Of the 44 patients assessed for minimal residual disease, 93% achieved negative MRD (71% of them at CR).
The most frequent grade 3 or grade 4 toxicities reported included prolonged thrombocytopenia (n = 34), infections during consolidation (n = 34), infections during induction (n = 25), hyperglycemia (n = 24), hypokalemia (n = 16) and hyperbilirubinemia (n = 8).
Sixty-five percent of patients were alive and 61% were in complete remission at the last follow-up.
Overall survival at 3 years was 52% and complete remission at 3-years was 76%.
The mini-hyper-CVD plus inotuzumab ozogamicin with or without rituximab (n = 46) results appeared superior to historical data of HCVAD with or without rituximab (n = 46) in a similar patients’ population. Patients who received HCVAD with or without rituximab had a 36% 3-year OS rate, according to the researchers.
“These results appear to be better than those achieved with hyper-CVAD [with or without] rituximab and may become the new standard of care for frontline treatment of older patients with ALL,” Sasaki said during the presentation. – by Ryan McDonald
Reference:
Sasaki K, et al. Abstract 588. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Kantarjian HM, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1509277.
Disclosure: Sasaki reports no relevant financial disclosures. Please see the full study for a list of all other relevant financial disclosures.