Yescarta (axicabtagene ciloleucel)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved October 2017

Specific Treatments:

relapsed or refractory large B-cell lymphomas

Therapeutic Areas

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General Information

Yescarta (axicabtagene ciloleucel) is a CD19-directed genetically modified autologous T cell immunotherapy.

Yescarta is specifically indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. 

Yescarta is supplied as a suspension for intravenous infusion. Each single infusion bag of Yescarta contains a suspension of chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL. The target dose is 2 × 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 108 CAR-positive viable T cells. 

Clinical Results

FDA Approval

The FDA approval of Yescarta was based on data from the ZUMA-1 pivotal trial. The single-arm, open-label, multicenter trial evaluated the efficacy of a single infusion of Yescarta in adult patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Following lymphodepleting chemotherapy, Yescarta was administered as a single intravenous infusion at a target dose of 2 × 106 CAR-positive viable T cells/kg (maximum permitted dose: 2 × 108 cells). The lymphodepleting regimen consisted of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 mg/m2 intravenously, both given on the fifth, fourth, and third day before Yescarta. Bridging chemotherapy between leukapheresis and lymphodepleting chemotherapy was not permitted. All patients were hospitalized for Yescarta infusion and for a minimum of 7 days afterward. In this study, 72% of patients treated with a single infusion of Yescarta (n=101) responded to therapy (overall response rate) including 51% of patients who had no detectable cancer remaining (complete remission; 95% CI: 41, 62). At a median follow-up of 7.9 months, patients who had achieved a complete remission had not reached the estimated median duration of response (95% CI: 8.1 months, not estimable [NE]). In the study, 13% of patients experienced grade 3 or higher cytokine release syndrome (CRS) and 31% experienced neurologic toxicities.

Side Effects

Adverse effects associated with the use of Yescarta may include, but are not limited to, the following:

  • cytokine release syndrome
  • fever
  • hypotension
  • encephalopathy
  • tachycardia
  • fatigue
  • headache
  • decreased appetite
  • chills
  • diarrhea
  • febrile neutropenia
  • infections-pathogen unspecified
  • nausea
  • hypoxia
  • tremor
  • cough
  • vomiting
  • dizziness
  • constipation
  • cardiac arrhythmias 

The Yescarta label comes with the following Black Box Warning:

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed. 

Mechanism of Action

Yescarta (axicabtagene ciloleucel) a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells. Studies demonstrated that following anti-CD19 CAR T cell engagement with CD19-expressing target cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades that lead to T cell activation, proliferation, acquisition of effector functions and secretion of inflammatory cytokines and chemokines. This sequence of events leads to killing of CD19-expressing cells.

Additional Information

For additional information regarding relapsed or refractory large B-cell lymphomas or Yescarta, please visit https://www.yescarta.com/