A 42-year old man with heavily-pretreated relapsed Philadelphia chromosome-positive, CD19-positive, pre-B acute lymphoblastic leukemia who was previously treated with CD19 chimeric antigen receptor-T (CAR-T) cell therapy experienced a complete response (CR) for 12 months following subsequent combination therapy with blinatumomab and ponatinib, according to a case study report published in Acta Haematologica.
Although salvage treatment with conventional chemotherapy in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is not very effective, anti-CD19 therapies such as CD19 CAR-T cell therapy approaches, as well as the use of blinatumomab, a monoclonal antibody classified as a CD19/CD3 bispecific T-cell engager (BiTE), have shown great promise in this setting. Although robust responses to CD19 CAR-T therapy have been reported following relapse on blinatumomab in B-ALL, use of the reverse sequence of anti-C19 therapies have not been previously reported.
In this case study, a 42-year old man diagnosed with pre-B ALL characterized as positive for the Philadelphia chromosome and the BCR-ABL fusion gene at the age of 36 years was reported to have received multiple prior treatments including induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation, several BCR-ABL targeted agents, and clofarabine followed by donor lymphocyte infusion, before receiving CD19 CAR-T cell therapy on a clinical trial. Upon disease relapse following CAR-T cell therapy, the patient received 4 courses of combination therapy with standard-dose blinatumomab and the tyrosine kinase inhibitor, ponatinib (30 mg daily), followed by ponatinib maintenance therapy. The patient achieved molecular remission and a CR lasting 12 months.
“[To their knowledge, this is] the first report of pre-B-ALL responding to CD19/CD3 BiTE therapy in combination with a tyrosine kinase inhibitor after failure of CD19 CAR-T therapy,” the study authors wrote.
“Further studies exploring the role of blinatumomab salvage, with or without a tyrosine kinase inhibitor, following CAR-T cell therapy or consolidation of partial responses to CAR-T cell therapy are warranted,” the authors wrote in conclusion.
- El Chaer F, Holtzman NG, Sausville EA, et al. Relapsed Philadelphia Chromosome-positive pre-B-ALL after CD19-directed CAR-T cell therapy successfully treated with combination of blinatumomab and ponatinib. Acta Haematol. 2019;141(2):107-110.