Brigatinib in Relapsed or Refractory ALK-Positive Anaplastic Large Cell Lymphoma

Although patients with ALK+ anaplastic large cell lymphoma (ALCL), a type of peripheral T-cell lymphoma (PTCL), are considered to have a favorable prognosis, relapse is not uncommon if multiple International Prognostic Index (IPI) risk factors, age ≥ 40, and beta-2 microglobulin ≥ 3 mg/L are present at diagnosis. For patients older than 40 years at diagnosis and beta-2 microglobulin ≥ 3 mg/L, progression-free survival (PFS) and overall survival (OS) is less than 50% at 2.5 years when treated with standard anthracycline-based induction therapy. Patients with ALK+ ALCL with 3 or more IPI risk factors have a 5-year PFS rate of only 20% to 30%. In total, approximately 40 to 65% of patients with ALCL develop recurrent disease after front-line chemotherapy and at relapse, the disease is historically resistant to conventional chemotherapy. Current FDA approved for treatment of relapsed or refractory PTCLs have a median PFS of 20 months and majority of patients relapse within 2 years. Despite ALK tyrosine kinase being an attractive target for management of relapsed or refractory ALK+ ALCL, ALK gene rearrangement makes cancer resistant to first and 2nd generation ALK inhibitors. Brigatinib is a next generation inhibitor with broad activity aganst a broad spetrum of resistant ALK mutants. Brigatinib has been shown to overcome mechanisms associated with resistane to 1st and 2nd generation ALK inhibitors. It is approved as 2nd line of treament in non small cell lung cancer patients. and is being tested in patients with relapsed or refractory ALK-positive ALCL.