Abecma
Abecma
Generic Name
Abecma
Mechanism
- CAR T‑cell platform: Autologous T cells are harvested, genetically modified using a lentiviral vector to express a BCMA‑specific scFv linked to CD137 and CD3ζ signaling domains, and expanded ex vivo.
- Targeted cytotoxicity: Upon infusion, CAR T cells recognize BCMA on myeloma cells, become activated, proliferate, and release cytotoxic granules (perforin, granzymes) and cytokines (IL‑2, IFN‑γ).
- B‑cell aplasia: Normal BCMA‑expressing plasma cells are eradicated, leading to hypogammaglobulinemia and a need for IgG replacement therapy.
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Pharmacokinetics
- Cell-based “drug”: Traditional PK parameters (C_max, T_max, AUC) are not applicable.
- Expansion & persistence: Rapid in‑vitro expansion (≈10‑200 fold) during manufacturing; post‑infusion expansion peaks within 1–3 days, followed by gradual decline.
- Half‑life: Median time to detectable persistence ≈ 23–37 days; functional persistence may extend up to 1 year in responders.
- Route: Intravenous infusion; no oral bioavailability.
- Clearance: CAR‑bearing T cells are cleared by immune-mediated apoptosis and differentiation into memory/effector populations; no hepatic or renal elimination pathways.
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Indications
- RRMM (relapsed/refractory multiple myeloma) after *≥3* prior therapy lines, including a proteasome inhibitor, an immunomodulatory drug, and an anti‑CD38 monoclonal antibody.
- Patients must have adequate organ function and no active CNS involvement.
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Contraindications
| Contraindications | Warnings |
| Inadequate organ function (hepatic, renal, cardiac) | Cytokine Release Syndrome (CRS) – life‑threatening; requires close monitoring and prompt intervention. |
| Uncontrolled infections (bacterial, viral, fungal) | Immune‑associated neurotoxicity (ICANS) – can result in seizures, dysphasia, and delirium. |
| Active autoimmune disease or immune‑mediated inflammation | B‑cell aplasia → hypogammaglobulinemia, recurrent infections. |
| Pregnancy or lactation | Tumor lysis syndrome – monitor electrolytes. |
| Prior CAR‑T therapy (within 12 months) | Infusion reactions – anaphylaxis risk increased with high cell doses. |
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Dosing
1. Leukapheresis → capture of autologous T cells.
2. Manufacturing (≈ 3–4 weeks) → lentiviral transduction, expansion, quality testing.
3. Lymphodepletion:
• *Fludarabine* 30 mg/m² × 3 days + *Cyclophosphamide* 500 mg/m² × 2 days.
4. Infusion:
• Target dose: 150–200 million CAR‑positive T cells (fixed dose, not weight‑based).
• Infusion over 45–60 minutes IV, preferably in a monitored setting (bleeding, CRT).
• Premedication: typically no routine steroids/anxiolytics, but anti‑hypersensitivity agents may be used in high‑risk cases.
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Adverse Effects
| Common (≥ 10 %) | Serious (≥ 1 %) |
| Infusion reaction (rash, pruritus) | CRS (≥ grade 3; ICU admission may be needed) |
| Fatigue | ICANS (≥ grade 3; seizures, altered mental status) |
| Anemia, neutropenia, thrombocytopenia | Severe infections (bacterial, viral, fungal) |
| Headache, nausea | Opportunistic infections (Pneumocystis, CMV, EBV) |
| Diarrhea, mucositis | B‑cell aplasia → hypogammaglobulinemia |
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Monitoring
- Baseline: CBC, CMP, serum albumin, immunoglobulins, viral serology (HBV, HCV, HIV).
- Post‑infusion:
- CTCAE‑graded CRS: vital signs, capillary refill, oxygen saturation hourly until stable.
- ICE score for neurotoxicity (every 6 h for first 14 days).
- CBC weekly for cytopenias.
- Serum albumin, creatinine daily for first 7 days.
- IL‑6, CRP if CRS suspected.
- Long‑term:
- Maintain IgG levels, administer IVIG prophylaxis if < 500 mg/dL.
- Monitor for late infections and quality‑of‑life.
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Clinical Pearls
- Early CRS grading is pivotal: a proactive tocilizumab (8 mg/kg) protocol reduces ICU stays without compromising efficacy.
- Steroid stewardship: Use dexamethasone only for grade 3–4 CRS or ICANS; avoid high steroid doses early to preserve CAR‑T expansion.
- Infusion speed matters: slower push rates (≥ 2 mL/min) have lower infusion‑related adverse events but do not affect efficacy.
- Vaccination gaps: Re‑vaccinate for pneumococcal, Haemophilus influenzae, and shingles ≥ 3 months post‑CAR‑T to prevent severe infections.
- Choice of lymphodepletion: A shorter fludarabine regimen (15 mg/m² × 3 days) can reduce hematologic toxicity, but its impact on CAR‑T persistence is still under investigation.
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• Key Takeaway
Abecma represents a paradigm shift in RRMM therapy, combining precision targeting of BCMA with the profound anti‑myeloma activity of CAR T cells. Mastery of its administration, vigilant monitoring for CRS/ICANS, and proactive infection prophylaxis are essential to maximize patient benefit.