Chimeric Antigen Receptor T Cell Therapy in Patients with Multiply Relapsed or Refractory Extramedullary Leukemia

Abstract

Autologous CD19-directed chimeric antigen receptor T lymphocyte (CAR-T) therapy is an approved and effective treatment for the management of patients with refractory and multiply relapsed B cell precursor acute lymphoblastic leukemia (B-ALL). Experience using this therapy in pediatric patients with extramedullary (EM) disease is limited, in part because these patients have frequently been excluded from clinical trials owing to concerns for an increased risk of immune effector cell-associated neurotoxicity syndrome (ICANS). We infused 7 patients with refractory or multiply relapsed B-ALL who presented with isolated EM relapse with tisagenlecleucel. Six patients had isolated central nervous system (CNS) leukemia, and 1 patient had an isolated testicular relapse. An initial complete response was seen in all patients, with 5 patients remaining in CAR-T-induced remission at a median of 18 months from first infusion. Reversible ICANS was seen in 1 patient with CNS leukemia. Durable B cell aplasia occurred in 3 patients, with a median time to B cell recovery of 6.5 months in the other patients. These data suggest that CAR-T therapy has promising safety and efficacy in treating EM leukemia, although definitive conclusions are limited by the small size of the cohort and limited follow-up period.

Testicular involvement of acute lymphoblastic leukemia in children and adolescents: Diagnosis, biology, and management

“…Although CAR‐T cells have mostly been used to treat bone marrow relapse, CAR‐T therapy has been effective for CNS leukemia, and CAR‐T cells have been observed beyond the blood‐brain barrier. Similarly, the control of testicular relapse with CAR‐T cells and their penetration of the blood‐testis barrier have been reported 78‐80 . If other studies confirm CAR‐T therapy to be effective for treating testicular relapse, this approach will be quite attractive because CAR‐T cells can control both medullary and extramedullary disease and are expected to have less gonadal toxicity.…”

Innovative and Promising Strategies to Enhance Effectiveness of Immunotherapy for CNS Tumors: Where Are We?

“…The therapeutic efficacy of CAR T-cells beyond hematopoietic cancers is less clear to date, there is limited documented information on antitumor activity against solid neoplasms. Several reports on CAR.CD19 T cells have proven that the genetically modified cells can cross the BBB ( 87 , 88 ). A patient with primary refractory DLBCL involving the brain parenchyma who achieved complete remission after CAR.CD19 T-cell infusion, in the absence of cytokine release syndrome or neurotoxic effects, provides strong support that CAR T cells have the capacity to penetrate the CNS ( 89 ).…”

Cytokine release syndrome and complete remission of extra medullary acute lymphoblastic leukemia of the breast with CAR‐T and radiation therapy

“…Currently, there are 53 reported patients with ALL with relapsed EM breast disease. Given its rarity, there are no standard management guidelines 2–9 …”

“…Given its rarity, there are no standard management guidelines. [2][3][4][5][6][7][8][9] As the immunotherapy landscape continues to evolve, chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable benefit in patients with relapsed/refractory B-cell ALL, but studies reporting its role in patients with EM disease is limited. 10,11 Here, we present the case of an adolescent/young adult patient with EM (breast) ALL.…”