Idelalisib

Evidence Level: L2

Predicted Indications: 6

Idelalisib

Pharmacist Assessment Report

Idelalisib: From Chronic Lymphocytic Leukaemia and Follicular Lymphoma to Mantle Cell Lymphoma

One-Sentence Summary

Idelalisib is an oral PI3K delta inhibitor originally used for B-cell malignancies, including chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma. The TxGNN model predicts it may be effective for Mantle Cell Lymphoma, with 5 clinical trials (all early-phase, none Phase 3) and 20 publications (mostly reviews and preclinical studies) currently supporting this direction. The evidence is early and does not yet show clear efficacy in this disease.

Quick Overview

Item	Content
Original Indication	Follicular lymphoma, CLL/SLL and other B-cell malignancies (the ARTG record compiled for this report has no indication text)
Predicted New Indication	Mantle cell lymphoma
TxGNN Prediction Score	0.9984
Evidence Level	L2 (see note below)
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	Hold

Note on evidence level: The data compiled for this report assigns L2, but the supporting trials for mantle cell lymphoma are Phase 1 studies plus one terminated Phase 2 study that enrolled mixed populations. By the stated criteria (a completed Phase 2/3 RCT) this is better read as L3–L4 for this specific indication, so L2 is likely generous. I have therefore recommended Hold rather than a more permissive decision.

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. From known pharmacology, idelalisib selectively inhibits PI3K delta, a key enzyme in B-cell receptor signalling that supports the survival and proliferation of malignant B cells.

Mantle cell lymphoma is a B-cell non-Hodgkin lymphoma that also depends on B-cell receptor and PI3K delta signalling, which is the mechanistic basis for the prediction. Preclinical work shows idelalisib suppresses mantle cell lymphoma cell growth through translation-regulatory mechanisms. Combination strategies (with a p300/CBP inhibitor or palbociclib) and resistance mechanisms (such as CBX5 loss) have also been described.

An important caveat: the literature notes that idelalisib has shown intrinsic resistance in some mantle cell lymphoma models. No Phase 3 evidence supports mantle cell lymphoma specifically.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT01088048	Phase 1	Completed	241	Safety of idelalisib combined with chemoimmunotherapy and other agents in relapsed/refractory indolent NHL, mantle cell lymphoma and CLL
NCT01838434	Phase 1/randomised Phase 2	Completed	106	Idelalisib plus lenalidomide versus lenalidomide alone in relapsed/refractory mantle cell lymphoma
NCT01796470	Phase 2	Terminated	66	Entospletinib plus idelalisib in relapsed/refractory haematological malignancies including mantle cell lymphoma; early termination limits conclusions
NCT02603445	Phase 1b	Completed	20	Dose escalation of BCL201 plus idelalisib in follicular and mantle cell lymphoma; small, safety-focused
NCT03151057	Phase 1	Terminated	16	Idelalisib as maintenance after allogeneic stem cell transplant in B-cell malignancies; different setting, small sample

No ANZCTR trial identifiers were available in the data compiled for this report.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
24795031	2014	Commentary	Cancer Discov	Idelalisib was effective in heavily pretreated mantle cell lymphoma patients
26841011	2016	Review	Cancer J	Idelalisib as a PI3K delta inhibitor in non-Hodgkin lymphoma
27342398	2017	Preclinical	Clin Cancer Res	Idelalisib reduces mantle cell lymphoma growth by inhibiting translation-regulatory mechanisms
33850273	2022	Preclinical	Acta Pharmacol Sin	A p300/CBP inhibitor (A-485) overcame idelalisib resistance in mantle cell lymphoma cells
38815797	2024	Preclinical	Cancer Lett	Idelalisib enhanced palbociclib activity via PLK1 in B-cell lymphoma
40466505	2025	Preclinical	Phytomedicine	CBX5 loss drives PI3K delta inhibitor resistance; propolis restores sensitivity
28775119	2017	Review	Haematologica	Incidence and management of toxicity with ibrutinib and idelalisib
24974852	2014	Review	Br J Haematol	Current regimens and novel agents for mantle cell lymphoma
26360791	2015	Review	Expert Opin Pharmacother	Treatment options for mantle cell lymphoma
28295729	2017	Review	J Intern Med	Targeting B-cell receptor signalling in B-cell malignancies

No randomised controlled trial publications were identified for this indication.

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 11162L	Zydelig	Tablet 150 mg (oral)	Indication text not available in the data compiled for this report

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (PI3K delta inhibitor)
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; at a minimum, full blood count and liver function are commonly monitored for this class
Handling Protection	Please refer to the PI and local cytotoxic/hazardous drug handling policies

Safety Considerations

Key Warnings and Contraindications: Not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI). The literature and trial records describe serious toxicities with idelalisib (hepatotoxicity, severe diarrhoea/colitis, pneumonitis and infections), and an increased rate of deaths and serious adverse events in some trials led to early terminations.
Drug Interactions: The interaction screen returned 100 interacting drugs; the first 20 are summarised here.
- Major: loperamide, triamcinolone, budesonide, eliglustat.
- Moderate: acarbose, doxycycline, hydrocortisone, pioglitazone, bupropion, aprepitant, dexamethasone, betamethasone, chenodeoxycholic acid, clarithromycin, saxagliptin, minocycline, eluxadoline (including some ophthalmic and nasal formulations).
- The full list should be reviewed before prescribing.

Conclusion and Next Steps

Decision: Hold

Rationale: The mantle cell lymphoma evidence consists of Phase 1 studies and one terminated Phase 2 study with mixed populations, supported mainly by preclinical and review literature. There is no Phase 3 data, reported resistance, and a well-documented serious toxicity profile. Mechanistic plausibility is reasonable, but it does not yet justify a move forward.

To proceed, the following is needed:

Mantle cell lymphoma-specific efficacy results (for example, published outcomes from NCT01838434)
Detailed mechanism of action data
The TGA-approved Product Information, including warnings, contraindications and approved indications
A risk-benefit comparison against established agents such as BTK inhibitors, given idelalisib’s toxicity profile
A safety monitoring plan covering hepatotoxicity, colitis, pneumonitis and infection

Note on other predicted indications

The data compiled for this report also covers nine further predicted indications. In brief:

B-cell neoplasm: Phase 3 RCT evidence exists (L1), but this largely overlaps with approved uses (CLL/SLL, follicular lymphoma) rather than being a new repurposing signal. Proceed with Guardrails.
Non-Hodgkin lymphoma, familial: Evidence reflects general indolent NHL, with no familial-specific data (L2). Research Question.
Myeloid leukaemia: Preclinical data and small, terminated early-phase studies (L3). Research Question.
Hodgkin lymphoma, CML (BCR-ABL1 positive) and colon adenocarcinoma: Little to no disease-specific clinical evidence (L4). Hold.
Two CLL/SLL molecular subtypes and small intestinal Burkitt lymphoma: Model prediction only (L5). Hold.
Disclaimer

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