Duvelisib

證據等級: L5

預測適應症: 10 個

Duvelisib: A PI3K-δ,γ Dual Inhibitor — TxGNN-Predicted Link to Hodgkin Lymphoma

One-Sentence Summary

Duvelisib is an oral PI3K-δ,γ dual inhibitor; this evidence pack does not record an original approved indication for it in this market (drug is currently unmarketed here). TxGNN's top-ranked prediction is Hodgkin's lymphoma, but the 11 clinical trials and 16 publications retrieved as supporting evidence all concern non-Hodgkin lymphoma subtypes (CLL/SLL, follicular, mantle cell, peripheral T-cell lymphoma) — none study classical Hodgkin lymphoma directly, so the evidence level for this specific label is only L4 with a Hold recommendation.

Quick Overview

Item	Content
Original Indication	Not recorded in this dataset — duvelisib is not currently marketed in this jurisdiction and no approved-indication text is available
Predicted New Indication	Hodgkin's lymphoma
TxGNN Prediction Score	99.94%
Evidence Level	L4
Germany Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Duvelisib's official mechanism-of-action field is a data gap in this evidence pack. However, the literature retrieved as supporting evidence consistently and independently describes duvelisib as an oral dual inhibitor of phosphoinositide 3-kinase δ and γ (PI3K-δ,γ), acting downstream of the B-cell receptor signaling pathway to suppress proliferation and survival of malignant B cells, while PI3K-γ inhibition additionally modulates the tumor microenvironment (macrophages/T-cells).

The automated relevance review embedded in this pack flags a significant mismatch for this rank-1 prediction: none of the 11 clinical trials or 16 publications retrieved under the "Hodgkin lymphoma" label actually enrolled or studied classical Hodgkin lymphoma (Reed-Sternberg cell biology). Every trial and paper instead concerns non-Hodgkin lymphoma subtypes — CLL/SLL, follicular lymphoma, mantle cell lymphoma, peripheral/cutaneous T-cell lymphoma — where duvelisib's mechanism is well established. This strongly suggests the TxGNN "Hodgkin lymphoma" score reflects an embedding-similarity artifact between lymphoma disease labels in the knowledge graph, rather than a genuine mechanistic signal specific to classical HL.

Important context: the same evidence pack contains a much stronger, differently-labeled signal — "B-cell neoplasm" (rank 9) — anchored by a completed pivotal Phase 3 trial (DUO, NCT02004522, n=319, duvelisib vs. ofatumumab in relapsed/refractory CLL/SLL) and rated L1/S3/"Proceed with Guardrails." The pack's own annotation for that entry, however, cautions that this largely reflects duvelisib's already-established therapeutic scope (CLL/SLL/FL) rather than a novel repurposing signal, and recommends resolving the drug-level data gaps (original indication, MOA) before that program is scored as "repurposing" versus "primary indication confirmation."

Clinical Trial Evidence

None of the following trials studied classical Hodgkin lymphoma specifically; all involve non-Hodgkin lymphoid malignancies retrieved under the "Hodgkin lymphoma" label.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02576275	Phase 3	Withdrawn	0	Duvelisib+bendamustine/rituximab vs. placebo in previously-treated indolent NHL — withdrawn, no data
NCT04803201	Phase 2	Suspended	170	Duvelisib-CHOEP vs. standard regimens in untreated CD30-negative peripheral T-cell lymphoma
NCT04379167	Phase 2	Unknown	140	PI3K-class agent (YY-20394) monotherapy in relapsed/refractory follicular NHL
NCT01882803	Phase 2	Completed	129	Duvelisib monotherapy in rituximab/chemo-refractory indolent NHL (FL, marginal zone, SLL)
NCT04038359	Phase 2	Completed	103	Intermittent vs. continuous duvelisib dosing schedules in indolent NHL
NCT01871675	Phase 1	Completed	48	Duvelisib + rituximab or bendamustine/rituximab in NHL/CLL
NCT05044039	Phase 1	Active, not recruiting	42	Duvelisib after CAR T-cell therapy to enhance CAR T persistence via PI3K inhibition
NCT02640833	Phase 1	Withdrawn	0	Duvelisib + venetoclax in R/R CLL/SLL/NHL — withdrawn
NCT04836832	Phase 1	Withdrawn	0	Duvelisib + acalabrutinib in R/R indolent NHL — withdrawn
NCT05065866	Phase 1	Completed	14	Duvelisib + BMS-986345 combination in lymphoid malignancy, dose-finding

Literature Evidence

PMID	Year	Type	Journal	Key Findings
36685572	2022	Systematic Review/Meta-analysis	Frontiers in Immunology	Safety/efficacy meta-analysis of duvelisib across R/R lymphoid neoplasm types
30799261	2019	Review	The Lancet Oncology	Overview of duvelisib in indolent non-Hodgkin lymphoma
29191916	2018	Phase 1 Trial	Blood	Foundational Phase 1 study establishing MTD (75 mg BID) and activity of duvelisib in advanced hematologic malignancies
31490009	2019	Cohort/Phase 1	American Journal of Hematology	Duvelisib + rituximab or bendamustine/rituximab in NHL/CLL
32356174	2020	Review	Current Treatment Options in Oncology	PI3K inhibitors, including duvelisib, as targeted therapy in lymphoma
33616890	2021	Review	Drugs	Novel therapeutic approaches, including duvelisib, in follicular lymphoma
27872741	2016	Review	Mediterranean Journal of Hematology and Infectious Diseases	Novel drugs, including duvelisib, in follicular lymphoma
32658557	2020	Review	Future Oncology	PI3K inhibitor class review in non-Hodgkin lymphoma treatment landscape
31580408	2019	Review	American Journal of Health-System Pharmacy	Summary of regulatory-approved targeted therapies for B- and T-cell lymphomas
36882482	2023	Preclinical	Scientific Reports	PI3Kγ/δ roles in mantle cell lymphoma proliferation/migration and duvelisib efficacy

Germany Market Information

Duvelisib is currently not marketed in Germany — no BfArM authorization records exist in this evidence pack (0 licenses on file).

Cytotoxicity

Duvelisib is an antineoplastic agent (oral small-molecule kinase inhibitor developed for hematologic malignancies).

Item	Content
Cytotoxicity Classification	Targeted therapy (PI3K-δ,γ dual inhibitor) — based on consistent description across retrieved literature; formal DrugBank category data not available in this evidence pack
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 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.

Conclusion and Next Steps

Decision: Hold

Rationale: The rank-1 TxGNN prediction (Hodgkin lymphoma) is not supported by relevant evidence — every retrieved clinical trial and publication concerns non-Hodgkin lymphoma, indicating a likely disease-label embedding artifact rather than a genuine repurposing signal for classical HL. In parallel, this candidate's drug-level data gaps (missing BfArM label warnings/contraindications — Blocking; missing MOA — High) prevent it from clearing the S1 safety pre-assessment stage regardless of indication.

To proceed, the following is needed:

Resolve DG001: obtain BfArM/product label warnings and contraindications
Resolve DG002: obtain confirmed MOA from DrugBank
Establish and document duvelisib's original/approved indication(s), currently unrecorded in this dataset
Disease-label-specific evidence re-review to confirm or rule out classical Hodgkin lymphoma relevance before advancing this specific candidate
If redirecting toward the stronger "B-cell neoplasm" signal (rank 9, L1/S3), first clarify whether that reflects genuine repurposing potential or overlap with duvelisib's already-established indication scope, and re-screen adjacent low-evidence CLL/SLL subtype entries (ranks 5–6) for the same embedding-artifact pattern seen at rank 1
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.