Evaluating ponatinib in recurrent Philadelphia chromosome positive central nervous system leukemia

This study aimed to investigate ponatinib combined with conventional therapy in recurrent Philadelphia chromosome-positive central nervous system leukemia with a BCR-ABL T315I mutation after allogeneic hematopoietic stem cell transplant. 

This study concluded that ponatinib may be effective for these patients.  

Philadelphia chromosome-positive leukemia (Ph+), is an aggressive subtype of leukemia. It includes acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (Ph+ CML). In Ph+ leukemia, the Philadelphia chromosome contains the abnormal BCR-ABL gene that helps leukemia cells to grow. The BCR-ABL T315I mutation is resistant to 1st and 2nd generation tyrosine kinase inhibitors (TKIs). Ponatinib (Iclusig) is a type of targeted therapy called a tyrosine kinase inhibitor (TKI). It is used for the treatment of Ph+ ALL and CML. 

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a procedure in which a person receives blood-forming stem cells from a genetically similar, but not identical, donor. This is often a sister or brother but could be an unrelated donor. Central nervous system leukemia (CNSL; leukemia in the brain) relapse is common in patients with Ph+ ALL or CML. It has a poor prognosis in patients with the T315I mutation who underwent allo-HSCT.  

It was unknown if ponatinib combined with conventional therapy in recurrent Ph+ CNSL with the BCR-ABL T315I mutation after allo-HSCT was safe and effective.

This study involved 9 patients with Ph+ CNSL and a T315I mutation. All patients had recurrent disease after allo-HSCT. 5 of the patients had Ph+ ALL and 4 had Ph+ CML. All patients received ponatinib combined with chemotherapy administered into the spinal canal (intrathecal). 

All patients achieved a deep molecular response (DMR – a sign of disease remission) and central nervous system remission (CNSR) at an average time of 1.5 months after ponatinib treatment. 2 patients (22.2%) experienced a second CNSL relapse due to ponatinib dose reduction but CNSR was achieved again after increasing the standard dose.  

6 patients (66.7%) developed graft versus host disease (GVHD). GVHD is where the transplanted cells begin to attack the patients. The average survival time after the first CNSL relapse after transplant was 18 months.  

This study concluded that ponatinib may be effective for recurrent Ph+ CNSL patients with BCR-ABL T315I mutation after allo-HSCT. 

This study included a very small number of patients. Larger studies are needed to confirm the results of this study.