Ofatumumab
| Evidence Level: L2 | Predicted Indications: 4 |
Table of Contents
- Ofatumumab
- Pharmacist Assessment Report
- Ofatumumab: From Acute Lymphoblastic Leukemia and Richter Syndrome to Follicular Lymphoma
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Ofatumumab: From Acute Lymphoblastic Leukemia and Richter Syndrome to Follicular Lymphoma
One-Sentence Summary
Ofatumumab is an anti-CD20 antibody. The TxGNN model (deep learning) predicts it may be effective for follicular lymphoma, with 11 clinical trials and 20 publications compiled for this direction, including several completed Phase 2 trials in follicular lymphoma itself.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute lymphoblastic/lymphocytic leukemia and Richter syndrome (relations recorded in the knowledge graph; the local licence records contain no indication text) |
| Predicted New Indication | Follicular lymphoma |
| TxGNN Prediction Score | 0.9970 |
| Evidence Level | L2 |
| India Market Status | Listed in a compiled Indian medicine price dataset (2 of 2) – CDSCO approval status is not included in this data |
| Number of Listed Products | 2 (valid: 2) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the compiled data. Based on known information, ofatumumab is a fully human anti-CD20 monoclonal antibody that binds a distinct epitope on CD20, involving both the small and large extracellular loops. It is thought to act through complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity.
Follicular lymphoma is a CD20-positive B-cell malignancy, so the drug’s target is expressed directly on the tumour cells. The original uses recorded in the knowledge graph are also B-cell or lymphoid malignancies. Complement-mediated killing may also explain activity in rituximab-refractory disease. The high TxGNN score is consistent with this biology.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01286272 | Phase 2 | Completed | 135 | Randomized: ofatumumab + bendamustine vs. the same plus bortezomib in untreated follicular lymphoma |
| NCT00494780 | Phase 2 | Completed | 59 | Randomized two-dose ofatumumab + CHOP in untreated follicular lymphoma |
| NCT01190449 | Phase 2 | Completed | 51 | Single-agent ofatumumab in previously untreated follicular NHL |
| NCT00394836 | Phase 2 | Completed | 116 | Single-arm ofatumumab in rituximab-refractory follicular lymphoma |
| NCT01077518 | Phase 3 | Terminated | 346 | Ofatumumab + bendamustine vs. bendamustine alone in rituximab-unresponsive indolent B-cell NHL |
| NCT02710643 | Phase 2 | Completed | 110 | MIRO: local radiotherapy with or without ofatumumab in stage I/II follicular lymphoma |
| NCT01239394 | Phase 2 | Completed | 43 | Ofatumumab as initial treatment of indolent B-cell lymphoma |
| NCT00823719 | Phase 2 | Completed | 61 | Ofatumumab + ICE or DHAP in relapsed or refractory aggressive B-cell lymphoma (DLBCL); not follicular-specific |
| NCT00742144 | Phase 1 | Completed | 6 | Ofatumumab monotherapy in Japanese patients with follicular lymphoma or CLL |
| NCT01119794 | Phase 2 | Terminated | 10 | Ofatumumab + bortezomib in relapsed or refractory low-grade NHL |
Two further trials (NCT01397591, terminated with 3 patients; NCT01263418, withdrawn with no patients) provide no usable data.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31174236 | 2019 | Randomized Phase 2 | Cancer | CALGB 50904: ofatumumab + bendamustine with or without bortezomib in untreated high-risk follicular lymphoma |
| 30723894 | 2019 | Phase 2 | Br J Haematol | CALGB 50901: single-agent ofatumumab in untreated low/intermediate-risk advanced-stage follicular lymphoma |
| 22389254 | 2012 | Multicenter single-arm trial | Blood | Ofatumumab monotherapy in rituximab-refractory follicular lymphoma (n=116); overall response rate was modest at about 10–13% |
| 22409295 | 2012 | Randomized Phase 2 | Br J Haematol | Ofatumumab (500 mg or 1000 mg) + CHOP as frontline treatment of follicular lymphoma |
| 38937025 | 2024 | Phase 2 | Lancet Haematol | FIL MIRO: radiotherapy plus MRD-driven immunotherapy in early-stage follicular lymphoma |
| 18390837 | 2008 | Phase 1/2 | Blood | First clinical use of ofatumumab in relapsed or refractory follicular lymphoma |
| 26043777 | 2015 | Review | Expert Opin Biol Ther | Activity of ofatumumab in CD20-positive non-Hodgkin lymphomas |
| 29934061 | 2018 | Review | Clin Lymphoma Myeloma Leuk | Evidence review of anti-CD20 regimens in relapsed or refractory CLL, DLBCL and follicular lymphoma |
| 32933335 | 2021 | Review | Expert Opin Biol Ther | Anti-CD20 treatment for B-cell malignancies |
| 24443277 | 2014 | Population PK analysis | J Clin Pharmacol | Pharmacokinetics of ofatumumab in CLL, follicular lymphoma and rheumatoid arthritis |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 10845 | Arzerra 1000mg Solution for Infusion | Vial of 50 ml solution for infusion | Not stated in the licence record |
| 8338 | Arzerra Injection | Vial of 3 injections | Not stated in the licence record |
Both are single-ingredient licences from Glaxo SmithKline Pharmaceuticals Ltd and are currently valid.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Immunotherapy (anti-CD20 monoclonal antibody) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert; blood counts are generally monitored in B-cell malignancy treatment |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: The data compiled for this report lists 80 interacting drugs. Examples flagged as Major include deferiprone, samarium (153Sm) lexidronam, adalimumab, baricitinib, certolizumab pegol, cladribine and clozapine. Moderate examples include alemtuzumab, azathioprine, anakinra, zidovudine, chloramphenicol and several vaccines (e.g., live cholera and anthrax vaccines). Many of these involve additive immunosuppression or myelosuppression.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several completed Phase 2 trials and publications directly study ofatumumab in follicular lymphoma, including randomized studies in untreated disease. However, the evidence is Phase 2 level. The one Phase 3 trial (NCT01077518) was terminated. Single-agent response in rituximab-refractory disease was modest, and the drug is already marketed in India, though the licence records give no indication text.
To proceed, the following is needed:
- Package insert warnings and contraindications (currently a blocking gap)
- Detailed mechanism-of-action data from DrugBank
- Confirmation of the approved indications on the two Indian licences
- Results and outcome review of the terminated Phase 3 trial NCT01077518
- A safety monitoring plan, including infection and immunosuppression-related interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.