Comparing treatment options for CML and ALL patients with the T315I mutation

This paper compared ponatinib (Iclusib) and stem cell transplantation in leukemia patients with an abnormality on the T315I gene. Patients with acute lymphoblastic leukaemia (ALL) positive for the Philadelphia chromosome and patients with chronic myeloid leukaemia (CML) were studied. Authors reported improved survival with ponatinib only among CML patients in the chronic phase. 

CML and ALL are cancers of the blood and bone marrow. Certain genetic changes in CML and ALL can make it more difficult to treat. About 20% of patients with relapsed or resistant CML show a specific mutation on the threonine-to-isoleucine gene at position 315 (T315I mutation). CML and ALL patients with the T315I mutation often become resistant to standard treatment.

ALL patients with the T315I mutation who are also positive for the Philadelphia chromosome (Ph-positive) have a particularly poor prognosis. The Philadelphia chromosome is an abnormally short chromosome that plays a role in the process that creates abnormal white blood cells characteristic of ALL.

Stem cell transplantation is considered an effective therapy for patients with high-risk leukemia. However, patients with the T315I mutation may benefit from treatment with ponatinib. Ponatinib is a tyrosine kinase inhibitor that blocks an enzyme that causes stem cells to develop into more white blood cells than the body needs.

The records of 184 leukemia patients with the T315I mutation were analyzed. Of these, 27 were Ph-positive ALL patients. 90 of the CML patients had chronic disease (stable and slowly progressing). 26 CML patients were diagnosed with accelerated disease. 41 CML patients had aggressive disease. Of the 184 patients included, 128 received ponatinib and 56 underwent a stem cell transplantation.

The overall survival rate (proportion who have not died from any cause since treatment) at 2 years was significantly increased among patients treated with ponatinib (36.5%). It was 55.8% for patients who underwent a stem cell transplant.

At 48 months, 72.7% of chronic CML patients who received ponatinib survived. This was significantly higher compared to those treated with a stem cell transplant (55.8%). No significant differences in survival were observed across patients with accelerated CML. However, ponatinib worsened survival for patients with aggressive CML. At 48 months, survival was 2.29 times lower with ponatinib compared to stem cell transplantation. 

Ponatinib also lowered overall survival 2.77-fold among patients with Ph-positive ALL compared to stem cell transplantation. Average overall survival with ponatinib-treated patients was 6.7 months. It was 32.4 months for patients who underwent a stem cell transplant.

The authors concluded that stem cell transplantation remains an important treatment option for CML and ALL patients with the T315I mutation. CML patients in the chronic phase may consider ponatinib as an alternative.

Larger studies that randomly assign patients to treatment groups are needed to confirm these results.