Alemtuzumab
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Alemtuzumab: From Relapsing-Remitting Multiple Sclerosis to Hepatic Infarction
One-Sentence Summary
Alemtuzumab is an anti-CD52 antibody that depletes lymphocytes, originally used to treat relapsing-remitting multiple sclerosis. The TxGNN model's top-ranked prediction is hepatic infarction, but this has no clinical trials and no publications behind it. Among the other candidates, syndrome with combined immunodeficiency has the most support (7 clinical trials and 8 publications). There, alemtuzumab acts as a transplant conditioning component rather than a direct treatment.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Relapsing-remitting multiple sclerosis (the Singapore licence record contains no approved indication text) |
| Predicted New Indication | Hepatic infarction (rank 1). For reference, the best-supported candidate is syndrome with combined immunodeficiency |
| TxGNN Prediction Score | 94.44% (hepatic infarction) |
| Evidence Level | L5 (hepatic infarction); L2 (combined immunodeficiency) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold (hepatic infarction); the combined immunodeficiency candidate is a research question only |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, alemtuzumab is an anti-CD52 monoclonal antibody that depletes T and B lymphocytes. This is the basis of its use in relapsing-remitting multiple sclerosis, where it resets an overactive immune system.
Hepatic infarction (rank 1): No mechanistic rationale is evident. Lymphocyte depletion has no known role in ischaemic hepatic necrosis. The high score is a computational prediction only, with no supporting trials or literature. The other top-ranked candidates, such as urothelial carcinoma subtypes and peliosis hepatis, likewise lack a clear mechanism and any clinical evidence.
Combined immunodeficiency (rank 2): This is the best-supported candidate. Alemtuzumab depletes host lymphocytes and is used in reduced-intensity or serotherapy conditioning before allogeneic stem cell transplantation. This helps engraftment and reduces graft-versus-host disease in primary immunodeficiencies such as SCID, CD40L deficiency, IPEX, XIAP deficiency and chronic granulomatous disease. It is a conditioning component, not a direct treatment of the immunodeficiency.
Hemophagocytic syndromes (ranks 9-10): The rationale is biologically plausible, because HLH is driven by hyperactivated T cells that alemtuzumab depletes. Evidence is limited to a case report in lupus-associated HLH and general reviews.
Hepatic veno-occlusive disease (rank 3): This is a complication of transplant conditioning, not a disease alemtuzumab would treat. The literature mentions alemtuzumab only as part of conditioning regimens in which the condition occurs as an adverse outcome, so there is a risk of harm rather than benefit.
Clinical Trial Evidence
No clinical trials are registered for hepatic infarction (the rank 1 prediction). The table below shows trials for the best-supported candidate, syndrome with combined immunodeficiency.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01962415 | Phase 2 | Recruiting | 100 | Reduced-intensity conditioning for transplant in children and young adults with non-malignant disorders, including immunodeficiencies. Most directly relevant |
| NCT01182675 | Phase 2 | Terminated | 7 | Stem cell transplant for paediatric SCID using alemtuzumab and plerixafor, avoiding chemotherapy conditioning. Underpowered |
| NCT00579137 | Phase 1/2 | Terminated | 3 | CD45 antibody plus alemtuzumab conditioning for SCID and other primary immunodeficiencies. Insufficient data |
| NCT01019876 | Phase 2/3 | Completed | 38 | Risk-adapted transplant for mixed donor chimerism in non-malignant diseases. The alemtuzumab effect is not isolated |
| NCT01652092 | Not applicable | Active, not recruiting | 57 | Standard-of-care allogeneic transplant guideline for primary immune deficiencies |
| NCT05463133 | Phase 1/2 | Recruiting | 50 | Alemtuzumab, busulfan and TBI-based conditioning for chronic granulomatous disease. Indirect relevance |
| NCT00152100 | Phase 1 | Completed | 4 | Haploidentical CD133 transplant in children with SCID. Alemtuzumab's role is unclear |
Literature Evidence
Literature for the best-supported candidate (combined immunodeficiency). No literature is available for hepatic infarction.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27543157 | 2016 | Cohort | Biol Blood Marrow Transplant | Alemtuzumab/fludarabine/melphalan reduced-intensity conditioning compared with myeloablative conditioning in chronic granulomatous disease |
| 29155317 | 2018 | Cohort | Biol Blood Marrow Transplant | Treosulfan and fludarabine conditioning in 160 children with primary immunodeficiency (UK experience) |
| 21325599 | 2011 | Cohort | Blood | Treosulfan-based conditioning in 70 children with primary immunodeficiency, with alemtuzumab |
| 23131490 | 2013 | Cohort | Blood | International survey of transplant for XIAP deficiency. Outcomes were poor, with reduced-intensity regimens mostly alemtuzumab-based |
| 26073206 | 2015 | Cohort | Pediatr Transplant | Single-centre transplant experience in hyper-IgM syndrome (CD40L defect) |
| 19471859 | 2009 | Case report | Immunol Res | FOXP3 expression after reduced-intensity transplant for IPEX syndrome |
| 15590388 | 2004 | Review | Haematologica | Infectious toxicity associated with alemtuzumab |
| 18502831 | 2008 | Case report | Blood | EBV-positive lymphoproliferative disease after alemtuzumab-CHOP in T-cell lymphoma |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14919P | LEMTRADA Concentrate for Solution for Infusion 12 mg/1.2 mL | Infusion, solution concentrate | Not stated in the available record |
Safety Considerations
- Drug Interactions: 100 interactions were recorded. The major-level ones in the displayed results are deferiprone and samarium (153Sm) lexidronam. Moderate-level interactions include:
- corticosteroids (hydrocortisone, betamethasone, budesonide, dexamethasone, prednisolone, prednisone, triamcinolone)
- acetylsalicylic acid
- anticoagulants (heparin, argatroban, lepirudin)
- radiopharmaceuticals and radioimmunotherapies (ibritumomab tiuxetan, tositumomab, iobenguane I-131, strontium-89)
- palifermin
- Literature signals: Alemtuzumab carries a documented risk of infection and immunosuppression (PMID 15590388). EBV-related lymphoproliferative complications have been reported (PMID 18502831). Late-onset hepatic veno-occlusive disease has been seen in conditioning regimens that include it.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction, hepatic infarction, rests on a computational score alone. It has no mechanistic rationale, trials or literature. The most evidence exists for combined immunodeficiency, but it comes from small, early-phase trials and single-centre series. Alemtuzumab is only one conditioning component in these, so this is a research question rather than a ready repurposing candidate.
To proceed, the following is needed:
- The package insert warnings and contraindications from the HSA, which are currently missing and block safety screening
- Detailed mechanism of action data
- For combined immunodeficiency, a study that isolates alemtuzumab's contribution to transplant outcomes, plus a review of infection and EBV-related risks
- For hemophagocytic syndromes, a review of the indirect evidence and further clinical data
- Confirmation of the approved indication and route compatibility for the Singapore licence
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.