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
- Australia Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Other Predicted Indications (Not Recommended at This Time)
- Disclaimer
Ofatumumab: From Acute Lymphoblastic Leukaemia and Richter Syndrome to Follicular Lymphoma
One-Sentence Summary
Ofatumumab is a fully human anti-CD20 monoclonal antibody. Predicted uses on this page come from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence; they are not approvals confirmed by Australian label text. The TxGNN model predicts it may be effective for follicular lymphoma, with 11 clinical trials and 20 publications compiled for this report. Several of these are Phase 2 studies of ofatumumab in follicular lymphoma itself.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute lymphoblastic leukaemia and Richter syndrome (relations recorded in the knowledge graph; no approved indication text is available in the Australian licence record) |
| Predicted New Indication | Follicular lymphoma |
| TxGNN Prediction Score | 0.9970 |
| Evidence Level | L2 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| 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. Ofatumumab is, however, a well-characterised fully human monoclonal antibody that binds CD20 on B cells. This binding is understood to kill cells through complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity.
Follicular lymphoma is a CD20-positive B-cell malignancy, so an anti-CD20 antibody is mechanistically well suited. The score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.
Note that the supplied data contain Phase 2 evidence (including a randomised trial and a multicentre study in rituximab-refractory disease) and one terminated Phase 3 trial, but no completed Phase 3 randomised trial.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01286272 | Phase 2 | Completed | 135 | Randomised: ofatumumab + bendamustine with or without bortezomib in untreated follicular lymphoma |
| NCT00394836 | Phase 2 | Completed | 116 | Single-arm study in follicular lymphoma refractory to rituximab |
| NCT02710643 | Phase 2 | Completed | 110 | MIRO: radiotherapy with or without ofatumumab in stage I/II follicular lymphoma |
| NCT00494780 | Phase 2 | Completed | 59 | Two-dose randomised trial of ofatumumab + CHOP in untreated follicular lymphoma |
| NCT01190449 | Phase 2 | Completed | 51 | Ofatumumab alone in previously untreated follicular non-Hodgkin lymphoma |
| NCT01239394 | Phase 2 | Completed | 43 | Initial treatment of indolent B-cell lymphoma (mixed histologies) |
| NCT00823719 | Phase 2 | Completed | 61 | Ofatumumab + ICE or DHAP chemotherapy in relapsed/refractory aggressive lymphoma (DLBCL) before stem cell transplant |
| NCT01077518 | Phase 3 | Terminated | 346 | Ofatumumab + bendamustine vs bendamustine in rituximab-unresponsive indolent B-cell NHL |
| NCT00742144 | Phase 1 | Completed | 6 | Safety and pharmacokinetics in Japanese patients with CD20+ follicular lymphoma or CLL |
| NCT01119794 | Phase 2 | Terminated | 10 | Ofatumumab + bortezomib in relapsed/refractory low-grade NHL; limited information |
Two further trials (NCT01397591, terminated with 3 patients; NCT01263418, withdrawn with no enrolment) provide no useful efficacy evidence.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31174236 | 2019 | Randomised Phase 2 | Cancer | Ofatumumab + bendamustine vs the same with bortezomib in untreated high-risk follicular lymphoma (CALGB 50904) |
| 22389254 | 2012 | Multicentre single-arm Phase 2 | Blood | Ofatumumab monotherapy in rituximab-refractory follicular lymphoma (n=116); overall response rate about 10-13% |
| 22409295 | 2012 | Phase 2 | Br J Haematol | Two doses of ofatumumab + CHOP in 59 untreated follicular lymphoma patients |
| 30723894 | 2019 | Phase 2 | Br J Haematol | Single-agent ofatumumab in untreated low/intermediate-risk advanced follicular lymphoma (CALGB 50901) |
| 38937025 | 2024 | Prospective Phase 2 | Lancet Haematol | FIL MIRO: local radiotherapy with residual-disease-driven immunotherapy in early-stage follicular lymphoma |
| 18390837 | 2008 | Phase 1/2 | Blood | First clinical use of ofatumumab in relapsed/refractory follicular lymphoma |
| 26043777 | 2015 | Review | Expert Opin Biol Ther | Ofatumumab in non-Hodgkin lymphomas |
| 29934061 | 2018 | Review | Clin Lymphoma Myeloma Leuk | Evidence-based review of anti-CD20 regimens in relapsed/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 across CLL, follicular lymphoma and rheumatoid arthritis (n=477) |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 12641H | Kesimpta | Solution for injection 20 mg in 0.4 mL pre-filled pen | Indication text not available in the licence record |
This is the only entry, and it is a pre-filled pen presentation. Its suitability for any oncology use cannot be assumed; dosing and formulation would need separate confirmation.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Immunotherapy (anti-CD20 monoclonal antibody) |
| Myelosuppression Risk | Please refer to the Product Information (PI) warnings and precautions |
| Emetogenicity Classification | Please refer to the Product Information (PI) warnings and precautions |
| Monitoring Items | Please refer to the PI; typically full blood count and liver function, with infection surveillance |
| Handling Protection | Please refer to the PI and local institutional policy |
Safety Considerations
Label warnings and contraindications were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for safety information.
Drug interactions: 80 interactions were recorded. Examples of those rated Major:
- Deferiprone
- Samarium (153Sm) lexidronam
- Adalimumab
- Baricitinib
- Certolizumab pegol
- Cladribine
- Clozapine
Moderate examples include alemtuzumab, azathioprine, anakinra, chloramphenicol, zidovudine, and several vaccines (anthrax, tetanus toxoid, live cholera). Many of these relate to additive immunosuppression or myelosuppression.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 2 studies, including randomised trials and published results, investigate ofatumumab directly in follicular lymphoma, and the anti-CD20 mechanism fits the disease. The efficacy signal is modest in rituximab-refractory disease, the only Phase 3 trial was terminated, and the sole Australian listing is a pre-filled pen product.
To proceed, the following is needed:
- Review of the TGA-approved PI for safety, warnings and contraindications
- Mechanism of action data confirmed from a reference source
- Comparative evidence against current standard anti-CD20 therapy in follicular lymphoma, ideally Phase 3
- Confirmation of an appropriate formulation, dose and supply route in Australia for lymphoma use
- A monitoring plan for infection, hepatitis B reactivation and immunosuppression-related interactions
Other Predicted Indications (Not Recommended at This Time)
| Predicted Indication | TxGNN Score | Evidence Level | Decision | Comment |
|---|---|---|---|---|
| Metastatic neoplasm | 0.9950 | L5 | Hold | One small pilot (n=10) in metastatic melanoma and no direct efficacy literature for the term as predicted |
| Malignant spiradenoma | 0.9948 | L5 | Hold | No trials or literature |
| Langerhans cell histiocytosis | 0.9934 | L5 | Hold | No trials or literature; no clear CD20-driven rationale |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.