FDA Approval Summary: Axicabtagene Ciloleucel for Relapsed or Refractory Large B-cell Lymphoma

Abstract

In October 2017, the FDA granted regular approval to axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. Efficacy was based on complete remission (CR) rate and duration of response (DOR) in 101 adult patients with relapsed or refractory large B-cell lymphoma (median 3 prior systemic regimens) treated on a single-arm trial. Patients received a single infusion of axicabtagene ciloleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. The objective response rate per independent review committee was 72% [95% confidence interval (CI), 62-81], with a CR rate of 51% (95% CI, 41-62). With a median follow-up of 7.9 months, the median DOR was not reached in patients achieving CR (95% CI, 8.1 months; not estimable, NE), whereas patients with partial remission had an estimated median DOR of 2.1 months (95% CI, 1.3-5.3). Among 108 patients evaluated for safety, serious adverse reactions occurred in 52%. Cytokine release syndrome and neurologic toxicities occurred in 94% and 87% of patients, respectively, leading to implementation of a risk evaluation and mitigation strategy.

Imaging CAR T cell therapy with PSMA-targeted positron emission tomography

“…Treatment of B cell malignancies, particularly those that express the CD19 surface marker, has been transformed by the appearance of CAR T cell therapy. According to ClinicalTrials.gov, there are currently 720 clinical trials under way that use CAR T cells, with objective response rates exceeding 70% for relapsed or refractory large B cell lymphoma (36). Significant effort is also under way to enable treatment of solid tumors using CAR T cells (37).…”

Toxicities of CD19 CAR‐T cell immunotherapy

“…CAR‐modified T (CAR‐T) cells targeting the B lineage molecule, CD19, have produced impressive results in patients with acute lymphoblastic leukemia (ALL), non‐Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia . The US Food and Drug Administration (FDA) has approved two CD19‐directed CAR‐T cell immunotherapies . Tisagenlecleucel was approved for the treatment of patients up to 25 years of age with B‐cell precursor ALL refractory or in second or later relapse after the ELIANA study showed minimal residual disease‐negative complete remission (CR) rates of 81%; and was later approved for adult patients with relapsed or refractory (R/R) large B‐cell lymphoma after two or more lines of systemic therapy after the JULIET study showed overall response (OR) and CR rates of 52% and 40%, respectively .…”

UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells

“…Its high potential is reflected by the impressive success of two CD19-specific CAR T cell therapeutics, axicabtagene ciloleucel and tisagenlecleucel that were approved by the U.S. Food and Drug Administration in 2017 for treatment of B cell malignancies. [6][7][8] CARs are composed of an extracellular tumor-specific antigen binding domain linked to intracellular signaling domains from activating immune receptors (e.g. CD3ζ, CD28, 4-1BB).…”