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Nilotinib with low-intensity chemotherapy may be viable in older patients with Ph+ALL
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SAN FRANCISCO — The addition of nilotinib to chemotherapy yielded improved OS in a cohort of older patients with Philadelphia-positive acute lymphoblastic leukemia, according to findings presented here.
Oliver G. Ottmann, MD, professor of hematology at Goethe University in Frankfurt, Germany, said that the combination of chemotherapy and tyrosine kinase inhibitors is the gold standard for Philadelphia-positive ALL, a diagnosis in which poor outcomes are typically reported in older patients. Patients in the current study were older than 55 years.
“We only allowed patients with minimal prior treatment,” Ottmann said. “These are de novo newly diagnosed patients.”
The treatment regimen began with pre-phase dexamethasone with optional cyclophosphamide, after which nilotinib (Tasigna, Novartis Oncology) was administered at 400 mg twice daily starting with induction therapy and given continuously thereafter. During induction, nilotinib was combined with intravenous vincristine and dexamethasone for 4 weeks. Consolidation cycles consisted of nilotinib, methotrexate, asparaginase and cytarabine, while the maintenance phase consisted of nilotinib, methotrexate, dexamethasone and vincristine.
“The treatment schedule was relatively complicated, as it usually is for ALL,” Ottmann said.
Study protocols also called for assessment of minimal residual disease at two time points, according to Ottmann. “One was early and occurred after induction, and the later one was used to assess the impact of induction,” he said.
Ottmann reported findings for 47 patients with a minimum duration of follow-up. Complete hematological remission occurred in 87% of the cohort. The failure rate was 4%, with a 2% rate of induction death. Six percent of patients discontinued before complete remission assessment. “The median time to achieve this response was 6 weeks,” Ottmann said. “This seems to be a highly effective treatment, with only a few relapses at this time.”
The OS rate at 30 months was 67.1% for the full cohort and 72.7% for those without stem cell transplantation.
Analysis of minimal residual disease indicated that continued treatment increased the depth of response, according to Ottmann.
“Looking at MRD negativity, approximately 80% of patients achieved a major molecular response,” he said, and added that the proportion of patients who reached BRC-ABL negativity was 26.3% during treatment.
“Nilotinib combined with age-adapted, low-intensity chemotherapy is highly effective therapy for elderly Ph+ ALL patients Ottmann concluded.
For more information:
Ottmann OG. Abstract #798. Presented at: Presented at: ASH Annual Meeting and Exhibition; Dec. 6-9, 2014; San Francisco.
Disclosure: Ottmannreports a consulting relationship, receiving honoraria and research funding associations with Novartis.