Breyanzi^® (lisocabtagene maraleucel): Clinical Profile & Patient Journey Guide

Breyanzi is the first CD19 CAR‑T therapy with a defined cellular dose and a precise 1:1 ratio of CD4+ to CD8+ T‑cells. This engineered consistency aims to provide more predictable efficacy and a potentially more favorable safety profile compared to products with variable cell compositions.

Breyanzi is an autologous CD19‑directed CAR‑T cell therapy with a distinct manufacturing approach:

1. T‑Cell Collection: Patient's own T‑cells are collected via leukapheresis.
2. Genetic Modification: T‑cells are transduced with a lentiviral vector encoding a CAR that recognizes CD19.
3. CAR Structure:
   • Targeting domain: Single‑chain variable fragment (scFv) derived from anti‑CD19 antibody
   • Costimulatory domain: 4‑1BB (same as Kymriah), which promotes T‑cell persistence and reduces exhaustion
   • Signaling domain: CD3ζ, which activates T‑cell cytotoxic function
4. Defined Dose Manufacturing:
   • CD4+ and CD8+ T‑cells are separated and modified independently
   • Cells are combined in a precise 1:1 ratio before infusion
   • Fixed dose: 100 million CAR‑positive cells (±20%)
   • This controlled composition aims to reduce variability between patients
5. Reinfusion: Patient receives lymphodepleting chemotherapy (fludarabine/cyclophosphamide), followed by single infusion of CAR‑T cells.
6. Mechanism: CAR‑T cells bind CD19 on B‑cells (normal and malignant), activate cytotoxic response, and persist long‑term due to 4‑1BB signaling.

Large B‑Cell Lymphoma (LBCL) — Initial Approval February 2021

• Adult patients with relapsed or refractory large B‑cell lymphoma after two or more lines of systemic therapy
• Includes: DLBCL NOS, high‑grade B‑cell lymphoma, PMBCL, DLBCL arising from follicular lymphoma

Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) — Approval April 2024

• Adult patients with relapsed or refractory CLL or SLL after two or more prior lines of therapy
• FDA approval date: April 2024

Follicular Lymphoma (FL) — Approval April 2024

• Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more prior lines of therapy
• FDA approval date: April 2024

TRANSCEND NHL 001 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
• Notably, lower rates of severe CRS and ICANS compared to historical data from CD28 constructs
• Long‑term follow‑up shows sustained responses in a subset of patients
• Single‑arm study without control group

TRANSCEND CLL 004 Trial (CLL/SLL)

• Phase II, single‑arm, multicenter study
• Adult patients with r/r CLL or SLL after ≥2 prior lines (including BTK inhibitor and/or BCL2 inhibitor)
• Demonstrated high overall response rates with durable remissions
• Led to FDA approval for CLL/SLL indication in April 2024

TRANSCEND FL 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 April 2024

Breyanzi carries significant safety risks that require careful patient selection and monitoring. The following are based on FDA prescribing information and clinical trial data:

(Regulatory status may change. Always verify current approval status with regional regulatory authorities.)

Pricing (Approximate, Out‑of‑Pocket for International Patients)

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 — may be less intensive due to lower CRS rates
  • Long‑term follow‑up and monitoring
  • Immunoglobulin replacement therapy
• Total treatment episode cost can exceed $500,000‑$700,000 in the US when all components are included.

Insurance Coverage & International Access

• Coverage varies significantly by insurer, country, and specific indication.
• Breyanzi is available only at certified treatment centers (REMS‑certified in the US or equivalent).
• Our platform can facilitate introductions to certified treatment centers, but we cannot guarantee access or coverage.

Week 0: Decision & Preparation

• Consultation with oncologist · Discussion of risks, benefits, and alternatives · Selection of certified treatment center · Insurance pre‑authorization begins

Week 1‑2: Medical Records Transfer

• Collection of complete medical history, pathology reports, imaging · Secure transfer to treatment center · Initial remote consultation

Week 3‑4: Pre‑Treatment Evaluation

• In‑person consultation · Comprehensive evaluation: cardiac, pulmonary, hepatic, renal function · Patient and caregiver education on CRS/ICANS

Week 5‑6: Leukapheresis (T‑Cell Collection)

• 4‑6 hour procedure to collect T‑cells · Cells shipped to manufacturing facility

Week 7‑9: Manufacturing (Waiting Period)

• T‑cells are separated into CD4+ and CD8+ populations · Each population is modified independently · Combined in 1:1 ratio · Typical manufacturing time: 2‑3 weeks (potentially shorter than other products)

Week 10: Hospital Admission & Lymphodepletion

• Admission · 3 days of lymphodepleting chemotherapy (fludarabine + cyclophosphamide) · 1‑2 day rest period

Week 11: CAR‑T Infusion

• Single intravenous infusion (typically 30‑60 minutes) · Close monitoring for immediate reactions · Day 0 of post‑infusion monitoring

Week 12‑15: Intensive Monitoring (CRS/ICANS)

• Daily vital signs, neurologic assessments · Monitoring for CRS and ICANS · Treatment with tocilizumab and/or corticosteroids if needed

Week 16‑19: Discharge & Early Recovery

• Discharge if stable · Frequent outpatient follow‑up (2‑3 times per week) · Gradual return to normal activities

Month 2‑3: Continued Monitoring

• Weekly to biweekly outpatient visits · Blood tests · Imaging at day 30 and day 90

Month 4‑12: Long‑Term Follow‑Up

• Monthly visits, then every 2‑3 months · Annual follow‑up required for at least 15 years

What to Expect Emotionally

• Before treatment: Anxiety, hope, uncertainty are all normal
• During manufacturing: The waiting period (2‑3 weeks) can be especially stressful
• During CRS/ICANS: You may see confusion, personality changes, or physical symptoms — these are usually temporary
• After treatment: Adjustment period as patient recovers strength

Your Role in the Hospital

• You CAN: Provide emotional support, help with communication, assist with daily activities, advocate for patient needs
• You CANNOT: Make medical decisions, stay in the room 24/7, replace the medical team's expertise

Preventing Caregiver Burnout

• Recognize the signs: Exhaustion, irritability, feeling overwhelmed
• Ask for help: Family, friends, hospital social workers, support groups
• Take breaks — you cannot pour from an empty cup

Questions You Should Ask

• What are the signs of CRS/ICANS I should watch for?
• Who do I call if there's an emergency after hours?
• What medications does the patient need to take at home?
• When can the patient return to normal activities?

"Can I have children after Breyanzi?"

• The lymphodepleting chemotherapy and CAR‑T therapy may affect fertility. Discuss fertility preservation BEFORE treatment. Pregnancy after CAR‑T is possible but requires careful planning.

"Can I go back to work?"

• Most patients need 2‑3 months off work minimum. Return depends on recovery, blood counts, cognitive function, and energy levels.

"What if the treatment doesn't work?"

• Options may include other CAR‑T products, clinical trials, stem cell transplant, other targeted therapies, or palliative care.

"Does CAR‑T hurt?"

• Leukapheresis is well‑tolerated. The infusion is usually painless. Chemotherapy and CRS can cause side effects, but these are managed with medications.

"How long will I be away from home?"

• If local: 4‑6 weeks minimum. If traveling internationally: plan for 2‑3 months away from home.

"Can I get vaccinated after CAR‑T?"

• Live vaccines are avoided for at least 6 weeks before and 6 months after CAR‑T. Inactivated vaccines may be given after immune recovery.

Why Might Breyanzi Not Work?

• Antigen escape: Cancer cells may lose CD19 expression
• Insufficient CAR‑T expansion: Not enough CAR‑T cells persist
• Disease too advanced: Very high tumor burden may overwhelm the response
• Patient factors: Poor performance status, organ dysfunction

What Are the Next Options?

• Other CAR‑T products targeting different antigens (BCMA, CD22)
• Clinical trials with new constructs or bispecific antibodies
• Allogeneic stem cell transplant
• Palliative care focusing on quality of life

Wait times can be longer if manufacturing delays occur. International patients must factor in travel, accommodation, and extended stay costs. Not all patients are eligible.

These are general pharmacological differences. Individual patient responses vary. Treatment selection should be based on specific clinical circumstances, disease characteristics, and physician recommendation.