Wei Ying Jen, MD, of the Department of Leukemia at the University of Texas MD Anderson Cancer Center, discusses Philadelphia chromosome-positive acute lymphoblastic leukemia and treatment options.

Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) is the most frequent cytogenetic abnormality in adults with ALL. Patients with Ph-positive ALL usually demonstrate expression of a truncated version of the BCR-ABL protein called p190bcr-abl. Irrespective of age and breakpoint location, Ph-positive ALL carries a poor prognosis. Although remission rates are identical to those of Ph-negative ALL, relapse is almost universal and long-term survival remains rare.

As Dr. Jen explains, Ph-positive ALL has been difficult to treat, especially before the use of tyrosine kinase inhibitors (TKIs). These drugs have the ability to target the Philadelphia chromosome, an abnormal fusion between chromosomes 9 and 22. This makes them a viable treatment option to combine with traditional treatments such as chemotherapy or stem cell transplants.

The addition of TKIs to the treatment plans of Ph-positive ALL patients has developed greatly over the years. Initially through imatinib, then dasatinib, and now ponatinib and blinatumomab, a BiTE targeted at CD 19. These advancements have allowed for the novel concept of chemo-free treatment approaches, reducing side effects for patients.

A study published in 2017 looked at the feasibility of combining chemotherapy, blinatumomab and a TKI in Ph-positive acute lymphoblastic leukemia patients. Twelve adults with relapsed/refractory Ph-positive ALL or chronic myeloid leukemia in blast crisis were studied, treated with the combination blinatumomab and a TKI. All patients had previously failed at least 1 line of chemotherapy, including allogeneic stem cell transplantation, and 1 class of TKIs. Patients were treated for either overt hematologic relapse or persistent minimal residual disease following other regimens. From this study, the conclusion was drawn that the combination of blinatumomab with TKI is safe and effective in patients with relapsed/refractory Ph-positive disease.

Dr. Kim also stresses the importance of individualized treatment plans for Ph-positive ALL patients. Knowing a patient’s health history is imperative to developing a safe and effective combination of chemo, transplants, TKIs, and blinatumomab that is right for each individual.

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