Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden

Abstract

The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target cells may negatively impact the activation, persistence, and, as a consequence, the efficacy of subsequently used CAR-T cells. Here, we report a single-center experience in seven children with chemorefractory BCP-ALL treated with blinatumomab before CAR-T cell therapy either to reduce disease burden before apheresis (six patients) or as a bridging therapy (two patients). All patients responded to blinatumomab except one. At the time of CAR-T cell infusion, all patients were in cytological complete remission (CR). Four patients had low positive PCR-MRD, and the remaining three were MRD-negative. All patients remained in CR at day +28 after CAR-T infusion, and six out of seven patients were MRD-negative. With a median follow-up of 497 days, four patients remain in CR and MRD-negative. Three children relapsed with CD19 negative disease: two of them died, and one, who previously did not respond to blinatumomab, was successfully rescued by stem cell transplant. To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics. Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary.

Palbociclib and chemotherapy followed by blinatumomab consolidation to CAR‐T cell therapy in KMT2A‐rearranged, therapy‐related acute lymphoblastic leukemia

“…18 Moreover, the presence of KMT2Ar places patients treated with CAR T-cell therapy at risk for a lineage switch relapse. 17 Palbociclib combined with chemotherapy was safe and effective in attaining MRD-negative disease with cytogenetic and molecular remission from KMT2Ar t-ALL. Blinatumomab was also safely and effectively used to retain remission as a bridge to CAR T-cell therapy.…”

“…2,14 Blinatumomab has viable bridge to HSCT 15,16 and CAR T-cell therapy. 16,17 Our patient remains in remission at approximately 6 months after CAR T-cell infusion and under close surveillance due to risk of relapse given her t-ALL with t(4;11) translocation, early BCR post CAR-T therapy, and as 50% of patients with B-ALL relapse within the first year post-CD19 CAR T-cell therapy. 18 Moreover, the presence of KMT2Ar places patients treated with CAR T-cell therapy at risk for a lineage switch relapse.…”