Yescarta (axicabtagene ciloleucel)
Clinical Profile & Access Information
An independent clinical reference for Yescarta — a CD28-based CD19 CAR-T therapy for large B-cell lymphoma and follicular lymphoma.
Product Overview
| Brand Name | Yescarta |
| Generic Name | axicabtagene ciloleucel (axi-cel) |
| Manufacturer | Gilead Sciences / Kite Pharma |
| Target Antigen | CD19 → |
| CAR Construct | CD19 scFv + CD28 costimulatory domain + CD3ζ signaling domain |
| FDA Approval | October 2017 (second CAR-T therapy) |
| EMA Approval | August 2018 |
| Administration | Single intravenous infusion (autologous CAR-T cells) |
| Manufacturing | Patient's own T-cells collected via leukapheresis, genetically modified ex vivo using retroviral vector, expanded, and reinfused |
Yescarta was the second CAR-T therapy to receive FDA approval and the first to utilize a CD28 costimulatory domain, which confers distinct pharmacological characteristics compared to the 4-1BB domain used in Kymriah.
For general information on how CAR-T therapy works, please visit our CAR-T Cell Therapy Hub → For information on the CD19 target specifically, see CD19 CAR-T →
Mechanism of Action
Yescarta is an autologous CD19-directed CAR-T cell therapy with a distinct CAR structure:
- T-Cell Collection: Patient's own T-cells are collected via leukapheresis.
- Genetic Modification: T-cells are transduced with a retroviral vector encoding a CAR that recognizes CD19.
-
CAR Structure:
- Targeting domain: Single-chain variable fragment (scFv) derived from anti-CD19 antibody
- Costimulatory domain: CD28 (distinct from Kymriah's 4-1BB), which promotes rapid T-cell activation and potent cytotoxic response
- Signaling domain: CD3ζ, which activates T-cell cytotoxic function
- Expansion: Modified cells are expanded ex vivo to achieve therapeutic doses.
- Reinfusion: Patient receives lymphodepleting chemotherapy (fludarabine/cyclophosphamide), followed by single infusion of CAR-T cells.
- Mechanism: CAR-T cells bind CD19 on B-cells (normal and malignant), activate rapid cytotoxic response.
Key Pharmacological Distinction from Kymriah:
- CD28 domain drives more rapid and potent T-cell activation compared to 4-1BB
- This results in faster response onset but may be associated with higher rates of severe CRS
- CAR-T persistence may be shorter than 4-1BB constructs, though long-term durability is still observed in responders
- These differences influence patient selection, monitoring intensity, and toxicity management
Approved Indications
Yescarta is approved for the following indications (specific indications vary by region and approval date):
Large B-Cell Lymphoma (LBCL) — Initial Approval 2017
- Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy
- Includes:
- Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS)
- DLBCL arising from follicular lymphoma
- Primary mediastinal large B-cell lymphoma (PMBCL)
- High-grade B-cell lymphoma
- Transformed follicular lymphoma
- Note: This was the initial FDA approval (October 2017)
Follicular Lymphoma (FL) — Approval March 2021
- Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy
- FDA approval date: March 2021 (separate from initial LBCL approval)
- EMA indication: FL after two or more lines of systemic therapy
Important Clarification: Yescarta is NOT approved for Mantle Cell Lymphoma (MCL).
MCL is an approved indication for Tecartus (brexucabtagene autoleucel), a different CD19 CAR-T product from the same manufacturer.
Always verify specific indications with the most current prescribing information.
Note: Indications have evolved since initial approval. Always consult the most current regional prescribing information for specific line-of-therapy requirements.
Clinical Evidence Summary
Yescarta's approvals were based on pivotal multicenter clinical trials:
ZUMA-1 Trial (LBCL)
- Phase I/II, single-arm, multicenter study
- Adult patients with r/r LBCL after ≥2 prior lines
- Demonstrated high overall response rates with durable complete responses
- Long-term follow-up (median >60 months) shows sustained responses in a subset of patients
- Note: This was a single-arm study without control group
ZUMA-5 Trial (FL)
- Phase II, single-arm, multicenter study
- Adult patients with r/r FL after ≥2 prior lines
- Demonstrated high overall response rates with durable remissions
- Led to FDA approval for FL indication in March 2021
ZUMA-7 Trial (Second-Line LBCL)
- Phase III, randomized, open-label trial
- Compared Yescarta vs standard second-line therapy in patients with r/r LBCL within 12 months of first-line therapy
- Demonstrated superior event-free survival vs standard care
- Led to FDA approval for second-line treatment (earlier line of therapy) in 2022
Key Considerations:
- ZUMA-1 and ZUMA-5 were single-arm studies (no control group)
- ZUMA-7 was a randomized Phase III trial (higher level of evidence)
- Patient populations were highly selected (good performance status, adequate organ function)
- Results may not generalize to all patients in routine clinical practice
- Long-term safety data continue to be collected through post-marketing studies
Safety Profile
Yescarta carries significant safety risks that require careful patient selection and monitoring. The following are based on FDA prescribing information and clinical trial data.
Boxed Warnings (FDA)
Cytokine Release Syndrome (CRS):
- Occurs in majority of patients (typically within first 1-10 days post-infusion)
- CD28 construct may be associated with more rapid onset and higher severity compared to 4-1BB constructs
- Symptoms: fever, hypotension, hypoxia, organ dysfunction
- Severe (Grade 3-4) CRS occurs in approximately 15-20% of patients (slightly higher than Kymriah)
- Management: tocilizumab (IL-6 receptor antagonist), corticosteroids, supportive care
- Yescarta is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS) program
Neurologic Toxicities (ICANS):
- Immune effector cell-associated neurotoxicity syndrome (ICANS)
- May occur earlier and with higher frequency compared to 4-1BB constructs
- Symptoms: encephalopathy, aphasia, seizures, cerebral edema
- Typically occurs within first 8 days post-infusion
- Severe (Grade 3-4) ICANS occurs in approximately 20-25% of patients (higher than Kymriah)
- Management: corticosteroids, supportive care
Other Serious Adverse Reactions
- Prolonged cytopenias: Neutropenia, thrombocytopenia, anemia (may persist for weeks to months)
- Infections: Increased risk due to B-cell aplasia and hypogammaglobulinemia; prophylactic antimicrobials and immunoglobulin replacement may be required
- Hemophagocytic lymphohistiocytosis (HLH)/Macrophage activation syndrome (MAS): Rare but potentially fatal
- Hypogammaglobulinemia: Expected on-target effect due to B-cell aplasia; requires monitoring and immunoglobulin replacement
Long-Term Monitoring
- Patients must be monitored long-term for persistent cytopenias, infections, and secondary malignancies
- Annual follow-up recommended for at least 15 years per FDA requirement
Regulatory Status
| Region | Regulatory Authority | Approval Status | Approval Date |
|---|---|---|---|
| United States | FDA | Approved | Oct 2017 (FL: Mar 2021, 2nd-line: 2022) |
| European Union | EMA | Approved | August 2018 |
| United Kingdom | MHRA | Approved | 2018 |
| Japan | PMDA | Approved | 2020 |
| China | NMPA | Not approved | — |
Note: Regulatory status may change. Always verify current approval status with regional regulatory authorities.
Cost & Access Information
Pricing (Approximate, Out-of-Pocket for International Patients)
| Country | Approximate Cost (USD) | Notes |
|---|---|---|
| United States | $410,000 - $425,000 | List price; does not include hospitalization, supportive care, or management of complications |
| European Union | €320,000 - €373,000 | Varies by country; may be subject to national pricing agreements |
| Other Regions | Variable | Contact local Gilead/Kite representatives for pricing |
Total Treatment Cost Considerations
- The drug acquisition cost is only one component
- Additional costs include:
- Leukapheresis and cell collection
- Lymphodepleting chemotherapy
- Hospitalization (typically 2-4 weeks minimum)
- Management of CRS/ICANS (tocilizumab, corticosteroids, ICU care if needed) — may be more intensive due to CD28 construct
- Long-term follow-up and monitoring
- Immunoglobulin replacement therapy
- Total treatment episode cost can exceed $500,000-$800,000 in the US when all components are included
Insurance Coverage
- Coverage varies significantly by insurer, country, and specific indication
- Many insurers require prior authorization and documentation of eligibility criteria
- Patients should contact their insurance provider directly to verify coverage before treatment
International Access
- Yescarta is available only at certified treatment centers
- Treatment centers must be REMS-certified (US) or equivalent
- International patients must coordinate with certified centers in their region
- Our platform can facilitate introductions to certified treatment centers, but we cannot guarantee access or coverage
For patients exploring treatment options: Our platform can help you understand what records a treating center may need and facilitate introductions to certified centers. Request an Information-Based Case Review →
Comparison with Other CD19 CAR-T Products
Yescarta vs Kymriah (tisagenlecleucel):
| Feature | Yescarta (axi-cel) | Kymriah (tisa-cel) |
|---|---|---|
| Costimulatory Domain | CD28 | 4-1BB |
| Onset of Response | Faster (days) | Slower (weeks) |
| CRS Severity (Grade 3-4) | Higher (15-20%) | Lower (10-20%) |
| ICANS Severity (Grade 3-4) | Higher (20-25%) | Lower (5-15%) |
| CAR-T Persistence | Shorter (months) | Longer (years) |
| Approved Indications | LBCL, FL | B-ALL, DLBCL, FL |
| Manufacturing Vector | Retroviral | Lentiviral |
Note: These are general pharmacological differences. Individual patient responses vary. Treatment selection should be based on specific clinical circumstances, disease characteristics, and physician recommendation.