Ofatumumab
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
- Ofatumumab
- Ofatumumab: From Acute Lymphoblastic Leukaemia and Richter Syndrome to Follicular Lymphoma
Ofatumumab: From Acute Lymphoblastic Leukaemia and Richter Syndrome to Follicular Lymphoma
One-Sentence Summary
Ofatumumab is an anti-CD20 monoclonal antibody, originally listed for acute lymphoblastic/lymphocytic leukaemia and Richter syndrome in the knowledge graph used by the model. The TxGNN model predicts it may be effective for follicular lymphoma, with 11 clinical trials and 20 publications currently supporting this direction. The strongest evidence is at Phase 2 level (L2), with no completed Phase 3 trial testing ofatumumab in this disease.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute lymphoblastic/lymphocytic leukaemia; Richter syndrome (from the knowledge graph; no approved indication text is available in the Singapore licence records) |
| Predicted New Indication | Follicular lymphoma |
| TxGNN Prediction Score | 99.70% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Proceed with Guardrails |
Note: The top-ranked predictions are two molecular subtypes of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), each scored 99.77%. Neither has subtype-specific trials or publications (L4, Research Question). This report focuses on follicular lymphoma, the highest-ranked prediction with direct clinical evidence, and mentions CLL/SLL where relevant.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, ofatumumab is a fully human anti-CD20 antibody. Its efficacy in B-cell leukaemias has been studied, and mechanistically it may be applicable to other CD20-positive B-cell cancers.
Follicular lymphoma cells express CD20, the target of ofatumumab. The antibody binds a different epitope from rituximab. It is thought to kill B cells through complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Leukaemia and follicular lymphoma are both B-cell malignancies, so the link between the original and new indications is biologically coherent.
Clinical studies support this. They include a rituximab-refractory monotherapy study (PMID 22389254), randomized Phase 2 trials in untreated disease, and combination studies with chemotherapy. Important limits remain. Several trials were terminated or withdrawn with very small enrolment. The data also do not show whether ofatumumab is superior to rituximab.
Clinical Trial Evidence
The table lists the 10 most relevant of the 11 trials for follicular lymphoma.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01286272 | Phase 2 | Completed | 135 | Randomized: ofatumumab + bendamustine with or without bortezomib in untreated follicular lymphoma |
| NCT00494780 | Phase 2 | Completed | 59 | Two-dose randomized study of ofatumumab + CHOP in untreated follicular lymphoma |
| NCT01190449 | Phase 2 | Completed | 51 | Single-agent ofatumumab in previously untreated follicular lymphoma |
| 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 | Local radiotherapy with or without ofatumumab in stage I/II follicular lymphoma (MIRO) |
| NCT01239394 | Phase 2 | Completed | 43 | Ofatumumab as initial treatment of indolent B-cell lymphoma (mixed cohort) |
| NCT00823719 | Phase 2 | Completed | 61 | Ofatumumab + ICE or DHAP before autologous transplant in relapsed/refractory aggressive lymphoma |
| NCT00742144 | Phase 1 | Completed | 6 | Safety and pharmacokinetics in Japanese patients with follicular lymphoma or CLL |
| NCT01119794 | Phase 2 | Terminated | 10 | Ofatumumab + bortezomib in relapsed/refractory low-grade NHL; terminated early |
Two further trials add little: NCT01397591 (terminated, 3 patients) and NCT01263418 (withdrawn, 0 patients).
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22389254 | 2012 | Phase 2 study | Blood | Ofatumumab monotherapy in 116 rituximab-refractory follicular lymphoma patients; response rates of about 10–13% |
| 31174236 | 2019 | Randomized Phase 2 | Cancer | Ofatumumab + bendamustine with or without bortezomib in untreated high-risk follicular lymphoma (CALGB 50904) |
| 22409295 | 2012 | Phase 2 | Br J Haematol | Two doses of ofatumumab + CHOP as first-line treatment in 59 patients |
| 30723894 | 2019 | Phase 2 | Br J Haematol | Single-agent ofatumumab in untreated low/intermediate-risk follicular lymphoma (CALGB 50901) |
| 38937025 | 2024 | Phase 2 | Lancet Haematol | Radiotherapy plus MRD-driven immunotherapy in early-stage follicular lymphoma (FIL MIRO) |
| 18390837 | 2008 | Phase 1/2 | Blood | First clinical use of ofatumumab in relapsed/refractory follicular lymphoma |
| 29934061 | 2018 | Evidence review | Clin Lymphoma Myeloma Leuk | Review of anti-CD20 regimens in relapsed/refractory CLL, DLBCL and follicular lymphoma |
| 26043777 | 2015 | Review | Expert Opin Biol Ther | Activity of ofatumumab in CD20-positive B-cell lymphomas |
| 32933335 | 2021 | Review | Expert Opin Biol Ther | Current status of anti-CD20 treatment for B-cell malignancies |
| 24443277 | 2014 | Pharmacokinetic study | J Clin Pharmacol | Population pharmacokinetics across CLL, follicular lymphoma and rheumatoid arthritis |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16100P | KESIMPTA Solution for Injection in Pre-filled Syringe 20mg/0.4ml | Injection, solution | Not stated in the licence record |
| SIN16101P | KESIMPTA Solution for Injection in Pre-filled Pen 20mg/0.4ml | Injection, solution | Not stated in the licence record |
Both licences are valid single-ingredient products from Novartis Pharma Stein AG. These are the 20 mg pre-filled presentations; the available data do not describe an intravenous oncology presentation for Singapore.
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; at minimum, complete blood count with differential and liver function. Monitor for hepatitis B reactivation and infection, as is standard for anti-CD20 therapy |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for safety information.
Drug Interactions: The interaction screen identified 80 interacting drugs. Examples of Major interactions include:
- Deferiprone
- Samarium (153Sm) lexidronam
- Adalimumab
- Baricitinib
- Certolizumab pegol
- Cladribine
- Clozapine
Examples of Moderate interactions include strontium chloride Sr-89, roflumilast, chloramphenicol, zidovudine, alemtuzumab, anakinra, azathioprine, canakinumab, and several vaccines (tetanus toxoid, anthrax, live cholera). Many of these involve additive immunosuppression or myelosuppression.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 2 trials, including randomized ones and a rituximab-refractory study, support ofatumumab activity in follicular lymphoma. No completed Phase 3 trial supports it in this disease (the Phase 3 trial NCT01077518 was terminated), which caps the evidence at L2. Package insert safety data are also missing. Comparative benefit against rituximab is not established.
Other predictions in the data:
- CLL/SLL (rank 5, L1, Proceed with Guardrails): This has the strongest evidence, including Phase 3 trials and meta-analyses. However, the Phase 3 trials used ofatumumab as the comparator, and this may be on-label or near-label use rather than true repurposing. Confirm this.
- CLL/SLL molecular subtypes (ranks 1–2, L4): No subtype-specific trials or literature. Research Question only.
- Metastatic neoplasm (L3), leukaemia susceptibility (L4): Hold.
- Malignant spiradenoma, Langerhans cell histiocytosis, histiocytic and dendritic cell neoplasm, childhood mediastinal neurogenic neoplasm (all L5): Hold. These are prediction-only, with weak or no mechanistic rationale.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Health Sciences Authority (HSA) (blocking gap)
- Detailed mechanism of action data from DrugBank
- Confirmation of the approved indications and available presentations for the Singapore licences (the 20 mg pre-filled products listed carry no indication text)
- Head-to-head or comparative evidence against rituximab in follicular lymphoma
- A safety monitoring plan, including hepatitis B screening, infection risk, and review of the major drug interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.