Obinutuzumab
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Obinutuzumab
- Obinutuzumab: From Acute Lymphoblastic Leukaemia / Richter Syndrome to Pre-germinal Centre CLL/SLL
Obinutuzumab: From Acute Lymphoblastic Leukaemia / Richter Syndrome to Pre-germinal Centre CLL/SLL
One-Sentence Summary
Obinutuzumab is a glycoengineered type II anti-CD20 antibody, listed in the knowledge graph for acute lymphoblastic/lymphocytic leukaemia and Richter syndrome. The TxGNN model's top prediction is pregerminal center chronic lymphocytic leukemia/small lymphocytic lymphoma, but no clinical trials or publications were retrieved for this specific subtype. The strongest evidence in the data compiled for this report sits with the related predictions of follicular lymphoma (L1) and mantle cell lymphoma (L2), which are summarised below.
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 record) |
| Predicted New Indication | Pregerminal center chronic lymphocytic leukemia/small lymphocytic lymphoma |
| TxGNN Prediction Score | 99.21% |
| Evidence Level | L4 (for the top-ranked indication; follicular lymphoma L1, mantle cell lymphoma L2) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold (top-ranked indication); Proceed with Guardrails (follicular lymphoma) |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled records. Based on known information, obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody. It binds CD20 on B cells and, compared with rituximab, produces enhanced direct cell death, antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP).
The top two predictions are subtypes of CLL/SLL, a CD20-positive B-cell malignancy in which obinutuzumab is already established. The link is therefore plausible through the parent disease. However, the second-ranked subtype (IGHV-mutated CLL/SLL) falls within the approved CLL label, so it is not a true repurposing candidate.
The same CD20 logic applies to follicular lymphoma and mantle cell lymphoma, where the data compiled for this report include substantial trial and literature support. For follicular lymphoma, obinutuzumab is likely already an approved indication elsewhere, so this finding probably confirms an existing use rather than a new opportunity. Several other predictions (metastatic neoplasm, malignant spiradenoma, Langerhans cell histiocytosis) lack a CD20-based rationale.
Clinical Trial Evidence
No clinical trials were registered for the top-ranked prediction (pregerminal center CLL/SLL). The table below shows the most relevant trials for the best-supported prediction, follicular lymphoma.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05100862 | Phase 3 | Active, not recruiting | 799 | Zanubrutinib + obinutuzumab vs lenalidomide + rituximab in relapsed/refractory FL or MZL |
| NCT03817853 | Phase 4 | Completed | 114 | Safety of short-duration (90-minute) obinutuzumab infusion in untreated advanced FL |
| NCT02871219 | Phase 2 | Completed | 96 | Obinutuzumab + lenalidomide in untreated FL |
| NCT00825149 | Phase 1 | Completed | 137 | Obinutuzumab with CHOP, FC or bendamustine in CD20+ FL |
| NCT05929222 | Phase 3 | Recruiting | 190 | Radiotherapy alone vs radiotherapy + obinutuzumab in early-stage FL (GAZEBO) |
| NCT05045664 | Phase 3 | Recruiting | 100 | Low-dose radiotherapy + anti-CD20 antibody in early-stage FL |
| NCT03341520 | Phase 2 | Completed | 89 | Response-adapted radiotherapy + obinutuzumab in stage I/II nodal FL |
| NCT02391545 | Phase 1b/2 | Terminated | 55 | Duvelisib with rituximab or obinutuzumab in untreated FL |
| NCT01582776 | Phase 1b/2 | Completed | 317 | Obinutuzumab + lenalidomide in FL and aggressive B-cell lymphoma |
| NCT04796922 | Phase 3 | Withdrawn | 0 | Parsaclisib + rituximab/obinutuzumab; no patients enrolled, so no data |
For mantle cell lymphoma, the most direct trials include NCT02896582 (Phase 2, completed, 86 patients, upfront obinutuzumab with DHAP and transplant), NCT04855695 (Phase 1/2, recruiting, 72 patients, acalabrutinib + venetoclax + obinutuzumab) and NCT02736617 (Phase 2, completed, only 10 patients, obinutuzumab + ibrutinib). No Phase 3 trial of obinutuzumab in MCL was identified.
Literature Evidence
Nothing was retrieved for the top-ranked prediction. Key publications for follicular lymphoma and mantle cell lymphoma:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29856692 | 2018 | RCT | J Clin Oncol | GALLIUM: obinutuzumab vs rituximab chemoimmunotherapy in untreated FL (1,202 patients); effect of chemotherapy backbone |
| 37404773 | 2023 | RCT | HemaSphere | GALLIUM final analysis in untreated FL/MZL; obinutuzumab-based regimens improved progression-free survival in FL |
| 37506346 | 2023 | RCT (Phase 2) | J Clin Oncol | ROSEWOOD: zanubrutinib + obinutuzumab vs obinutuzumab alone in relapsed/refractory FL |
| 28976863 | 2017 | Trial report | N Engl J Med | Obinutuzumab-based vs rituximab-based chemotherapy in untreated advanced FL |
| 31296423 | 2019 | Phase 2 | Lancet Haematol | GALEN: obinutuzumab + lenalidomide in relapsed/refractory FL |
| 38669626 | 2024 | Randomised comparison | Blood | Obinutuzumab vs rituximab in transplant-eligible MCL (propensity-matched LyMa-101 comparison) |
| 39437708 | 2025 | Phase 2 | Blood | Zanubrutinib + obinutuzumab + venetoclax in first-line TP53-mutated MCL |
| 33181832 | 2021 | Phase 1/2 | Blood | Ibrutinib + obinutuzumab + venetoclax in relapsed and untreated MCL |
| 32971036 | 2020 | Phase 2 | Lancet Haematol | Obinutuzumab + DHAP induction in transplant-eligible untreated MCL (LyMa-101) |
| 35856239 | 2022 | Review | Future Oncol | Comprehensive review of obinutuzumab in B-cell malignancies |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14827P | GAZYVA Concentrate for Solution for Infusion 1000mg/40ml (Roche Diagnostics GmbH) | Infusion, solution concentrate | Not stated in the licence record |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy / immunotherapy (anti-CD20 monoclonal antibody), not a conventional cytotoxic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions (neutropenia is a recognised concern with anti-CD20 antibody regimens, especially combined with chemotherapy) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential; infection surveillance; hepatitis B status (a reactivation concern for anti-CD20 agents) |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: 81 interactions were recorded. Major-level interactions include deferiprone, samarium (153Sm) lexidronam, adalimumab, baricitinib, certolizumab pegol, cladribine and clozapine. Moderate-level interactions include strontium chloride Sr-89, roflumilast, chloramphenicol, zidovudine, alemtuzumab, azathioprine, anakinra, canakinumab, alefacept, and several vaccines (tetanus toxoid, anthrax, live cholera). Many of these relate to additive immunosuppression or myelosuppression, and live vaccines warrant particular caution.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold (top-ranked indication, pregerminal center CLL/SLL); Proceed with Guardrails (follicular lymphoma)
Rationale:
- The top-ranked prediction and its IGHV-mutated sibling are CLL/SLL subtypes with no subtype-specific trials or literature. They fall under a disease for which obinutuzumab is already used, so they are not true repurposing opportunities.
- Follicular lymphoma has the strongest support (L1): large randomised comparisons (GALLIUM) and several Phase 2/3 trials. Obinutuzumab is probably already approved for it elsewhere, so this is more a confirmation of an existing indication. Mantle cell lymphoma (L2) is supported by Phase 2 data only. The metastatic neoplasm, malignant spiradenoma and Langerhans cell histiocytosis predictions lack a credible CD20 rationale.
To proceed, the following is needed:
- The Singapore package insert (warnings, contraindications and approved indications), since the licence record lists no indication text. The safety review cannot proceed without it.
- Confirmation of whether follicular lymphoma is already within the Singapore-approved indications.
- Detailed mechanism of action data from DrugBank.
- For mantle cell lymphoma, Phase 3 evidence or regulatory precedent before any further step.
- A safety monitoring plan covering infection, hepatitis B reactivation and the immunosuppressive drug interactions above.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.