Efficacy

YES
There's proven efficacy

//Compelling Responses1

In the ZUMA-1 (study design) pivotal trial, YESCARTA (axicabtagene ciloleucel) was proven effective in adult patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL). Patients receiving YESCARTA achieved a best objective response rate (ORR) of 72% (73/101). Response duration at a median follow-up of 7.9 months was longer in patients who achieved complete remission (not reached), as compared to patients with a best response of partial remission (2.1 months).

//ZUMA-1 Pivotal Trial*1

ZUMA-1 (study design) evaluated the efficacy and safety of YESCARTA single-infusion immunotherapy to address the unmet medical need for patients with relapsed or refractory aggressive B-cell NHL.1

Study Design

In the ZUMA-1 Phase 2, open-label, single-arm study, 101 adult patients received YESCARTA therapy in 22 academic centers.2 Patients received lymphodepleting chemotherapy: 500 mg/m2 IV cyclophosphamide and 30 mg/m2 IV fludarabine (-5, -4, -3 days before infusion). YESCARTA was administered as a single infusion to a target dose of 2 x 106 viable CAR T cells/kg body weight (maximum of 2 x 108 viable CAR T cells). All patients were hospitalized and monitored for YESCARTA infusion for a minimum of 7 days afterward.

Challenging Population

Patients had refractory disease to the most recent therapy or relapse within 1 year after autologous hematopoietic stem cell transplantation (HSCT). 76% had diffuse large B-cell lymphoma (DLBCL), 16% had transformed follicular lymphoma, and 8% had primary mediastinal large B-cell lymphoma. 77% of patients were refractory to ≥2nd line of therapy and 21% had relapsed ≤1 year after autologous HSCT.*

//Response Rates†1

The best objective response rate (ORR) was 72% (73/101; 95% CI: 62, 81), with 51% (52/101) of patients achieving complete remission (CR), and 21% (21/101) of patients achieving partial remission (PR). Median time to response was 0.9 months (range: 0.8-6.2 months).

Of the 52 patients who achieved CR, 14 initially had stable disease (7 patients) or PR (7 patients), with a median time to improvement of 2.1 months (range: 1.6-5.3 months).

//Duration of Response†‡1

The median duration of response (DOR) for all responders was 9.2 months [95% CI: 5.4, NE]. The median DOR if best response was a CR was not reached (95% CI: 8.1, NE); if best response was a PR, the median DOR was 2.1 months (95% CI: 1.3, 5.3).

Chart showing the median duration of response (DOR) for YESCARTA®

Median age was 58 years (range: 23-76 years) and patients had a median of 3 prior therapies (range: 1-10). Patients with a history of CNS disorders or autoimmune disease requiring systemic immunosuppression were ineligible.

Data reflect results from the ZUMA-1 pivotal trial at a median follow-up of 7.9 months. Efficacy was established on the basis of CR rate and DOR, as determined by an independent review committee.

DOR is measured from the date of first objective response to the date of progression or death from relapse or toxicity.

YESCARTA® logo
Available at
Authorized Treatment Centers
//IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

  • 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.
  • YESCARTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA REMS.

Cytokine Release Syndrome (CRS): CRS occurred in 94% of patients, including 13% with ≥ Grade 3. Among patients who died after receiving YESCARTA, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to infusion of YESCARTA. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

Neurologic Toxicities: Neurologic toxicities occurred in 87% of patients. Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks, with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade 3 or higher occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures occurred with YESCARTA. Fatal and serious cases of cerebral edema have occurred in patients treated with YESCARTA. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities. Monitor patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion and treat promptly.

YESCARTA REMS: Because of the risk of CRS and neurologic toxicities, YESCARTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA REMS. The required components of the YESCARTA REMS are: Healthcare facilities that dispense and administer YESCARTA must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after YESCARTA infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer YESCARTA are trained about the management of CRS and neurologic toxicities. Further information is available at www.YESCARTAREMS.com or 1-844-454-KITE (5483).

Hypersensitivity Reactions: Allergic reactions may occur. Serious hypersensitivity reactions including anaphylaxis may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in YESCARTA.

Serious Infections: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients, and in 23% with ≥ Grade 3. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. YESCARTA should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after YESCARTA infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and YESCARTA infusion. Grade 3 or higher cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after YESCARTA infusion.

Hypogammaglobulinemia: B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following YESCARTA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment.

Secondary Malignancies: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following YESCARTA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions: The most common adverse reactions (incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.

INDICATION

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy 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.

Limitation of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.

References: 1. YESCARTA [package insert]. Santa Monica, CA: Kite Pharma; 2017. 2. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544.