Inotuzumab ozogamicin with bosutinib for relapsed/refractory Philadelphia chromosome-positive ALL or lymphoid blast phase of CML

This study aimed to investigate if a combination of inotuzumab ozogamicin (InO; Besponsa) and bosutinib (Bo; Bosulif) was safe and effective in patients with relapsed/refractory (r/r) Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) or lymphoid blast phase (BP) chronic myeloid leukemia (CML).  

This study concluded that this treatment combination was well tolerated and effective in these patients.  

BP-CML has a large number of young leukemia cells in the bone marrow. Is very similar to ALL. Patients with Ph+ ALL or BP-CML usually have a poorer prognosis. Ph+ leukemia means that certain types of leukemia, particularly ALL or CML have a genetic abnormality that makes the illness more aggressive. These patients commonly relapse after standard treatments or stop responding to these treatments. Newer immunotherapies are promising for these patients.

InO is an immunotherapy where an immune protein (monoclonal antibody) is combined with an anti-cancer chemotherapy drug. It is used for the treatment of r/r ALL. Bo is a type of targeted therapy known as a tyrosine kinase inhibitor (TKI). It is used for the treatment of chronic myeloid leukemia (CML).  

It was unknown if combining InO and Bo was safe and effective for patients with r/r Ph+ ALL or BP-CML. 

This study involved 18 patients with r/r Ph+ ALL or BP-CML. All patients had between one and five prior treatments. Patients were treated with a combination of InO and Bo. The average follow-up was 44 months. The maximum dose of Bo without side effects that led to stopping treatment was 400mg daily.  

The most common severe side effects were low levels of platelets (blood cells involved in clotting) and low white cell counts, as well as pneumonia, rash, and increased liver enzymes. 

83% of patients had a complete response (no signs of cancer left) after treatment. 81% of patients had a complete cytogenetic response (no leukemia cells are Ph+) after an average of 1 month. Response to treatment lasted for 7.7 months on average.

The average overall survival was 13.5 months. 61% of patients achieved negative measurable residual disease (MRD). Negative MRD means there is no disease detected after treatment. 33% of patients had a stem cell transplant after achieving a complete response.  

This study concluded that InO with Bo combination was well tolerated and effective in patients with r/r Ph+ ALL and BP-CML. 

This was a small phase 1/2 study. Further studies with more participants are needed. This study was funded by Pfizer, the manufacturer of both InO and Bo.