Targeted Therapy Effective in Elderly Patients with Philadelphia-Positive Acute Lymphocytic Leukemia

While rates of remission among elderly patients with leukemia continue to improve, the outlook remains poor among those with a disease subtype present in nearly one-third of adults with acute lymphocytic leukemia known as Philadelphia-positive ALL (Ph+ ALL).

Nilotinib (Tasigna®) and Chemotherapy for First-Line Treatment in Elderly Patients with De Novo Philadelphia Chromosome/BCR-ABL1 Positive Acute Lymphoblastic Leukemia (ALL): A Trial of the European Working Group for Adult ALL (EWALL-PH-02)

This Phase II study evaluated the efficacy of the tyrosine kinase inhibitor nilotinib in combination with a low-intensity chemotherapy regimen to treat patients 55 or older with newly diagnosed Ph+ ALL. Patients received 400 mg of nilotinib twice daily with initial chemotherapy and then continuously during subsequent phases of chemotherapy for up to two years. Of 36 evaluable patients, 35 (97%) experienced complete responses, with 31 of 35 patients remaining in complete remission. Four patients relapsed after a median follow up of 211 days. Complete molecular remission, defined as the absence of mutations in the blood, was reached in 30 percent of patients after initial therapy and 42 percent during a subsequent phase known as consolidation. No patients died during initial therapy, though there were 34 reports of serious adverse events, including infections and neutropenic fever.

“Our results strongly support adding this targeted therapy to standard chemotherapy to help elderly ALL patients achieve remission without significant toxicity,” said lead study author Oliver G. Ottmann, MD, of Goethe University in Frankfurt, Germany. “This study, which joins several others evaluating treatments for elderly patients with Ph+ ALL, offers physicians valuable information to improve outcomes among these patients. We hope that additional study will further illuminate this drug’s positive effects and lead to its eventual approval as a treatment in this setting.”