Duvelisib
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Using the Evidence Pack you provided (candidate TW-DB11952-multi, DUVELISIB), here is the evaluation report. Note upfront: the top-ranked prediction (Hodgkin lymphoma) carries an explicit disease-entity mismatch warning embedded in the evidence pack itself — I've kept the template's predicted_indications[0] as the report subject per your spec, but flagged this prominently rather than glossing over it, and pointed to the stronger-evidence alternative (B-cell neoplasm, rank 9) in the conclusion.
Duvelisib: From CLL/SLL and Follicular Lymphoma to Hodgkin's Lymphoma
One-Sentence Summary
Duvelisib is a dual PI3K-δ/γ inhibitor originally approved for relapsed/refractory chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) and follicular lymphoma. The TxGNN model's top prediction points to Hodgkin's Lymphoma, but on closer inspection, the 11 clinical trials and 16 publications cited as supporting evidence almost all describe Non-Hodgkin Lymphoma (NHL) populations (indolent NHL, follicular lymphoma, CLL/SLL, PTCL) rather than classical Hodgkin lymphoma — no trial in this evidence set actually enrolls Hodgkin lymphoma patients.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Relapsed/refractory CLL/SLL and relapsed/refractory follicular lymphoma (drawn from cited literature, e.g. PMID 30430368, 38423708 — no Taiwan-specific approved indication text is on file) |
| Predicted New Indication | Hodgkin's Lymphoma ⚠️ (see mismatch caveat below) |
| TxGNN Prediction Score | 99.94% |
| Evidence Level | L4 |
| Taiwan Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is flagged as a data gap (DG002) in this evidence pack. Based on information available in the cited literature, Duvelisib is a small-molecule, orally administered dual inhibitor of phosphoinositide 3-kinase delta and gamma (PI3K-δ/γ) (PMID 30430368, 38423708). It blocks B-cell receptor (BCR) signaling and disrupts PI3Kγ-mediated tumor microenvironment support, a mechanism central to several B-cell and T-cell lymphoid malignancies. Its efficacy in CLL/SLL and follicular lymphoma is well established (first global approval 2018, per PMID 30430368), and mechanistically this BCR/PI3K-pathway dependency is shared broadly across lymphoid neoplasms.
However, the repurposing rationale for classical Hodgkin lymphoma specifically is weak. The evidence pack's own analysis flags this: "⚠️ Disease entity mismatch: the 11 trials and most literature listed here actually target Non-Hodgkin Lymphoma (indolent NHL, follicular lymphoma, CLL/SLL) rather than classical Hodgkin lymphoma — the two differ fundamentally in pathophysiology and treatment target (cHL is defined by Reed-Sternberg cells and PD-1/PD-L1-driven immune escape, not the atypical B-cell BCR-signaling dependency seen in NHL). No trial in this set directly enrolls Hodgkin lymphoma patients." This should be treated as a probable data-labeling error (NHL/HL name confusion) rather than a genuine mechanistic signal, and the mechanistic extrapolation to Hodgkin lymphoma remains unsupported by direct evidence.
By contrast, the evidence pack's rank-9 candidate, B-cell neoplasm, is supported by a completed Phase 3 pivotal trial (NCT02004522, the DUO trial) and reflects Duvelisib's actual approved indication space — this is a substantially stronger, evidence-backed repurposing signal than the Hodgkin lymphoma prediction (see Conclusion).
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04379167 | Phase 2 | Unknown | 140 | Single-arm study of YY-20394 (a duvelisib analog) in relapsed/refractory follicular NHL. Grade C — status unknown, population not confirmed as classical HL. |
| NCT05923502 | N/A | Not Yet Recruiting | 200 | Real-world observational study (CHANT) of Duvelisib capsules in Non-Hodgkin's Lymphoma — explicitly NHL, not HL. |
| NCT04803201 | Phase 2 | Suspended | 170 | Randomized study of chemo ± Duvelisib in CD30-negative peripheral T-cell lymphoma; suspended. |
| NCT01882803 | Phase 2 | Completed | 129 | Duvelisib monotherapy in refractory indolent NHL. Grade C — title explicitly "Non-Hodgkin Lymphoma," disease entity does not match. |
| NCT04038359 | Phase 2 | Completed | 103 | Compared two intermittent dosing schedules of Duvelisib in indolent NHL; dosing-schedule study, not HL-specific. |
| NCT05044039 | Phase 1 | Active, Not Recruiting | 42 | Duvelisib following CAR T-cell therapy to improve CAR-T persistence in lymphoma post-CAR-T relapse; not HL-specific. |
| NCT04836832 | Phase 1 | Withdrawn | 0 | Duvelisib + acalabrutinib in relapsed/refractory indolent NHL; withdrawn, no data generated. |
| NCT02640833 | Phase 1 | Withdrawn | 0 | Duvelisib + venetoclax in relapsed/refractory CLL/SLL/NHL; withdrawn, no data generated. |
| NCT05065866 | Phase 1 | Completed | 14 | Duvelisib + BMS-986345 dose-finding study in lymphoid malignancy. |
| NCT01871675 | Phase 1 | Completed | 48 | Duvelisib (IPI-145) + rituximab or bendamustine/rituximab in relapsed/refractory lymphoma or CLL. |
One additional trial (NCT02576275, Phase 3, Withdrawn, 0 enrolled) was excluded from this table as it generated no data.
None of the above trials enroll a classical Hodgkin lymphoma population.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36685572 | 2022 | Systematic Review/Meta-analysis | Frontiers in Immunology | Meta-analysis of Duvelisib safety/efficacy across relapsed/refractory lymphoid neoplasm subtypes — covers NHL/CLL populations, not classical HL specifically. |
| 30799261 | 2019 | Review | The Lancet. Oncology | Commentary on Duvelisib in indolent Non-Hodgkin lymphoma. |
| 31580408 | 2019 | Review | Am J Health-Syst Pharm | Summarizes approved targeted therapies for B- and T-cell lymphomas, including Duvelisib. |
| 33616890 | 2021 | Review | Drugs | Novel therapy approaches in follicular lymphoma, including PI3K inhibitors. |
| 32356174 | 2020 | Review | Curr Treat Options Oncol | Reviews PI3K inhibitors (including Duvelisib) as targeted therapy in lymphoma generally; no HL-specific data. |
| 33132100 | 2021 | Review | Clin Lymphoma Myeloma Leuk | Discusses next-generation PI3K inhibitors' potential in B-cell NHL. |
| 29191916 | 2018 | Phase 1 clinical study | Blood | Original Phase 1 dose-escalation study establishing Duvelisib's clinical activity in advanced hematologic malignancies (CLL, NHL subtypes). |
| 36882482 | 2023 | Preclinical/Mechanistic | Scientific Reports | Shows PI3Kγ/δ inhibition disrupts mantle cell lymphoma (an NHL subtype) proliferation and migration. |
| 27872741 | 2016 | Review | Mediterr J Hematol Infect Dis | Reviews novel drugs, including PI3K inhibitors, in follicular lymphoma. |
| 32658557 | 2020 | Review | Future Oncology | Reviews PI3K-class inhibitor use in Non-Hodgkin lymphoma. |
No publication in this evidence set specifically studies classical Hodgkin lymphoma.
Taiwan Market Information
Duvelisib currently holds no marketing authorization in Taiwan (market_status: 未上市 / Not Marketed; total_licenses: 0). No license records are available to tabulate.
Cytotoxicity
Duvelisib is an antineoplastic agent (approved for hematologic malignancies — CLL/SLL, follicular lymphoma), so this section applies.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (small-molecule PI3K-δ/γ dual inhibitor) — not a conventional cytotoxic chemotherapeutic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions (no quantified toxicity data in this evidence pack; the literature notes PI3K inhibitors as a class carry a "severe toxicity profile" that has led to restricted use — PMID 35899388, 33275709) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
Please refer to the package insert for safety information. (Key warnings, contraindications, and DDI data are all listed as data gaps in this evidence pack; DG001 — TFDA package insert warnings/contraindications — is flagged as a Blocking gap, meaning this candidate cannot proceed to the S1 safety pre-screen until resolved.)
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence cited for the Hodgkin lymphoma prediction is built almost entirely on Non-Hodgkin Lymphoma trials and literature — a probable disease-entity mislabeling rather than genuine mechanistic support — leaving the actual HL-specific evidence base at essentially zero. Combined with a Blocking safety data gap (no TFDA package insert on file) and no Taiwan market presence, this candidate does not meet the threshold to proceed.
To proceed, the following is needed:
- Verify and correct the disease-entity labeling on the NCT/PMID records currently mapped to "Hodgkin's Lymphoma" (likely an NHL/HL confusion) before re-scoring this candidate
- Obtain the TFDA package insert (warnings, contraindications) to close Blocking gap DG001 and enable the S1 safety pre-screen
- Obtain confirmed mechanism-of-action documentation from DrugBank to close High-severity gap DG002
- If genuine interest in Hodgkin lymphoma remains, a dedicated early-phase trial enrolling a confirmed classical HL population would be required — no such trial currently exists
- Recommend evaluating rank-9 "B-cell neoplasm" as the priority candidate instead — it is supported by L1 evidence (completed Phase 3 DUO trial, NCT02004522) and aligns with Duvelisib's already-established global approval in CLL/SLL and follicular lymphoma, making it a substantially stronger repurposing case within this same evidence pack
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.