Ofatumumab
| Evidence Level: L2 | Predicted Indications: 4 |
Table of Contents
- Ofatumumab
- Pharmacist Assessment Report
- Ofatumumab: From Acute Lymphoblastic Leukaemia and Richter Syndrome to Follicular Lymphoma
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Ofatumumab: From Acute Lymphoblastic Leukaemia and Richter Syndrome to Follicular Lymphoma
One-Sentence Summary
Ofatumumab is an anti-CD20 antibody; its original uses include acute lymphoblastic/lymphocytic leukemia and Richter syndrome. The TxGNN model predicts it may be effective for follicular lymphoma, with 11 clinical trials and 20 publications compiled for this direction. Several completed Phase 2 trials directly study follicular lymphoma, but no completed Phase 3 trial with reported results is included.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute lymphoblastic/lymphocytic leukaemia and Richter syndrome (relations recorded in the knowledge graph; the local licence record contains no indication text) |
| Predicted New Indication | Follicular lymphoma |
| TxGNN Prediction Score | 0.9970 |
| Evidence Level | L2 |
| Canada Market Status | Marketed (marketed DINs: 1 of 1) |
| Number of DINs | 1 (marketed: 1) |
| Number of approvals | 1 licence (1 DIN) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on the mechanistic rationale compiled, ofatumumab is a fully human anti-CD20 monoclonal antibody. It binds a distinct epitope on CD20 (the small and large extracellular loops) and kills cells through complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity.
Follicular lymphoma is a CD20-positive B-cell malignancy, so the drug’s target is directly present in the disease. The score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, such as the leukemia and lymphoma conditions linked to ofatumumab, not biological evidence. Activity in rituximab-refractory disease is plausible because of the different epitope and stronger complement activation.
Note that the conditions above are relations recorded in the knowledge graph, not approved indications. The Canadian licence record in the data has no indication text.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00394836 | Phase 2 | Completed | 116 | Single-arm study of ofatumumab in follicular lymphoma refractory to rituximab |
| NCT01286272 | Phase 2 | Completed | 135 | Randomised: ofatumumab + bendamustine with or without bortezomib in untreated follicular lymphoma |
| NCT00494780 | Phase 2 | Completed | 59 | Randomised two-dose ofatumumab + CHOP in untreated follicular lymphoma |
| NCT01190449 | Phase 2 | Completed | 51 | Single-agent ofatumumab in previously untreated follicular lymphoma |
| NCT01239394 | Phase 2 | Completed | 43 | Ofatumumab as initial treatment of indolent B-cell lymphoma |
| NCT02710643 | Phase 2 | Completed | 110 | MIRO: local radiotherapy with or without ofatumumab in stage I/II follicular lymphoma |
| NCT00823719 | Phase 2 | Completed | 61 | Ofatumumab + ICE or DHAP before autologous transplant in relapsed/refractory aggressive lymphoma (DLBCL) |
| NCT01077518 | Phase 3 | Terminated | 346 | Ofatumumab + bendamustine vs bendamustine alone in rituximab-unresponsive indolent B-cell NHL |
| NCT00742144 | Phase 1 | Completed | 6 | Safety and pharmacokinetics in Japanese patients with CD20-positive follicular lymphoma or CLL |
| NCT01119794 | Phase 2 | Terminated | 10 | Ofatumumab + bortezomib in relapsed/refractory low-grade NHL; too small to be informative |
One further Phase 2 trial (NCT01397591, terminated, 3 patients) and one withdrawn trial (NCT01263418, 0 patients) provide no usable evidence.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31174236 | 2019 | RCT (Phase 2) | Cancer | CALGB 50904: ofatumumab + bendamustine with or without bortezomib in untreated high-risk follicular lymphoma |
| 22389254 | 2012 | Phase 2 trial | Blood | Ofatumumab monotherapy in rituximab-refractory follicular lymphoma (n=116); overall response rate about 10–13% |
| 22409295 | 2012 | Phase 2 trial | Br J Haematol | Ofatumumab + CHOP (two doses) as first-line treatment of follicular lymphoma |
| 30723894 | 2019 | Phase 2 trial | Br J Haematol | CALGB 50901: single-agent ofatumumab in untreated low/intermediate-risk follicular lymphoma |
| 38937025 | 2024 | Phase 2 trial | Lancet Haematol | FIL MIRO: local radiotherapy plus MRD-driven immunotherapy in early-stage follicular lymphoma |
| 18390837 | 2008 | Phase 1/2 trial | Blood | First clinical use of ofatumumab in relapsed or refractory follicular lymphoma |
| 29934061 | 2018 | Review | Clin Lymphoma Myeloma Leuk | Evidence-based review of anti-CD20 regimens in relapsed/refractory CLL, DLBCL and follicular lymphoma |
| 26043777 | 2015 | Review | Expert Opin Biol Ther | Ofatumumab activity in non-Hodgkin lymphomas |
| 24443277 | 2014 | Population PK analysis | J Clin Pharmacol | Pharmacokinetics in CLL, follicular lymphoma and rheumatoid arthritis |
| 35663281 | 2022 | Review | Leuk Res Rep | Immunotherapy in indolent non-Hodgkin lymphoma |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02511355 | KESIMPTA | Not listed | Not listed in the licence record |
Safety Considerations
Drug Interactions: 80 interactions were identified. Major-level examples include deferiprone, samarium (153Sm) lexidronam, adalimumab, baricitinib, certolizumab pegol, cladribine and clozapine. Moderate-level examples include alemtuzumab, azathioprine, anakinra, canakinumab, chloramphenicol, zidovudine and several vaccines.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 2 trials, including randomised studies, directly examine ofatumumab in follicular lymphoma and are published in peer-reviewed journals, which supports an L2 evidence level. Response in rituximab-refractory disease was modest (about 10–13%), and the one Phase 3 trial listed was terminated, so benefit over existing anti-CD20 options is not established.
To proceed, the following is needed:
- Review the results of the terminated Phase 3 trial (NCT01077518) and compare ofatumumab with rituximab and obinutuzumab in follicular lymphoma
- Obtain the package insert warnings and contraindications from Health Canada
- Obtain mechanism-of-action data from DrugBank
- Confirm that the licensed Canadian product (KESIMPTA) is relevant to the dose, formulation and route used in oncology trials, since its licence record lists no indication or dosage form
- Define a safety monitoring plan, including infection and immunosuppression risk given the interacting drugs
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.