Relapsed Philadelphia Chromosome-Positive Pre-B-ALL after CD19-Directed CAR-T Cell Therapy Successfully Treated with Combination of Blinatumomab and Ponatinib

Abstract

Adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with conventional chemotherapy have dismal outcomes. Novel immunotherapies targeting CD19, including the bispecific T-cell engager blinatumomab and chimeric antigen-receptor T (CAR-T) cells, have revolutionized the treatment of R/R B-ALL. Robust response rates to CAR-T cell therapy after blinatumomab have recently been reported, but it is unknown whether blinatumomab can be effective following failure of anti-CD19 CAR-T cell therapy. Herein, we describe a patient with Philadelphia chromosome-positive B-ALL who relapsed after CD19-directed CAR-T therapy, but subsequently responded to the combination of blinatumomab and the tyrosine kinase inhibitor ponatinib, with the achievement of a complete remission lasting 12 months.

Mechanisms of Relapse After CD19 CAR T-Cell Therapy for Acute Lymphoblastic Leukemia and Its Prevention and Treatment Strategies

“…Hence, the combination regimen of Ponatinib and Blinatumomab is expected to address the relapse issues after CAR T-cell therapy. El Chaer et al (70) first reported a patient with Ph+ B-ALL who developed CD19-positive relapse after CD19 CAR T-cells treatment and subsequently responded to the combination of blinatumomab and ponatinib, which is a type of TKI and achieved CR for 12 months, indicating that TKI plays a critical role in the induction and maintenance phases of Ph+ B-ALL therapy. This provides a new approach for the prevention of CD19-positive relapse after CAR T-cell therapy.…”

Immunotherapies and Combination Strategies for Immuno-Oncology

“…Multiple clinical trials are underway to evaluate the safety and efficacy of combination of CAR T cells with checkpoint blockade [ 113 , 153 ]. In a separate case report, a patient with Philadelphia chromosome-positive B-ALL, who relapsed after CD19 targeted CAR therapy, was treated with the combination of blinatumomab (bi-specific T cell engagers against CD19 and CD3) and ponatinib (multi-tyrosine kinase inhibitor) [ 115 ]. Remarkably, the patient responded and achieved complete remission lasting 12 months [ 115 ].…”

“…In a separate case report, a patient with Philadelphia chromosome-positive B-ALL, who relapsed after CD19 targeted CAR therapy, was treated with the combination of blinatumomab (bi-specific T cell engagers against CD19 and CD3) and ponatinib (multi-tyrosine kinase inhibitor) [ 115 ]. Remarkably, the patient responded and achieved complete remission lasting 12 months [ 115 ]. It remains to be seen, however, if concurrent combination of these drugs with CAR T cell therapy will result in similar efficacy.…”