What are the dosing regimen and approved indications for Turalio (pirtobrutinib) in adult patients with relapsed or refractory mantle‑cell lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma?

Turalio Dosing and Indications

Turalio (pexidartinib) is indicated exclusively for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations not amenable to surgical improvement, dosed at 250 mg orally twice daily with a low-fat meal. 1

Critical Clarification: Drug Identity Error

The question appears to conflate Turalio (pexidartinib) with pirtobrutinib (Jaypirca)—these are entirely different medications with distinct indications. The evidence provided discusses pirtobrutinib for hematologic malignancies (mantle cell lymphoma, CLL/SLL), while Turalio is FDA-approved only for TGCT, a solid tumor of the joints.

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Turalio (Pexidartinib) - Correct Information

Approved Indication

• Symptomatic tenosynovial giant cell tumor (TGCT) in adults with:
  • Severe morbidity OR functional limitations
  • Disease not amenable to improvement with surgery 1

Standard Dosing Regimen

• 250 mg orally twice daily (total daily dose: 500 mg)
• Must be taken with a low-fat meal (11-14 grams total fat)
• Avoid high-fat meals (55-65 grams fat)—increases drug exposure and hepatotoxicity risk 1
• Continue until disease progression or unacceptable toxicity 1
• Swallow capsules whole; do not open, break, or chew 1

Dose Modifications for Hepatotoxicity

First dose reduction: 375 mg daily (125 mg AM, 250 mg PM)
Second dose reduction: 250 mg daily (125 mg twice daily)
Permanently discontinue if unable to tolerate 125 mg twice daily 1

Specific Hepatotoxicity Thresholds:

• ALT/AST >10× ULN: Permanently discontinue immediately 1
• ALT/AST 5-10× ULN: Withhold, monitor twice weekly; resume at reduced dose if ≤3× ULN within 4 weeks 1
• ALT/AST 3-5× ULN: Withhold, monitor weekly; resume at reduced dose if ≤3× ULN within 4 weeks 1
• ALP >2× ULN + GGT >2× ULN: Permanently discontinue 1
• Total bilirubin ≥2× ULN or direct bilirubin >1.5× ULN: Permanently discontinue 1

Critical Safety Warnings

BLACK BOX WARNING: Hepatotoxicity 1

• Can cause serious and potentially fatal liver injury, including vanishing bile duct syndrome
• Monitoring and prompt cessation may NOT eliminate risk of fatal liver injury
• Available only through REMS program requiring:
  • Baseline liver function tests
  • LFTs every 2 weeks for first 2 months
  • Monthly thereafter during treatment
  • Prescriber and pharmacy certification 1

Common Pitfalls

1. Dietary error: Taking with high-fat meals significantly increases pexidartinib concentrations and hepatotoxicity risk—counsel patients on low-fat meal requirements 1
2. Inadequate monitoring: Hepatotoxicity can be rapid and severe; strict adherence to monitoring schedule is non-negotiable
3. Delayed discontinuation: Do not attempt dose reduction for severe hepatotoxicity (ALT/AST >10× ULN or significant bilirubin elevation)—permanent discontinuation is required 1

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Pirtobrutinib (Jaypirca) - For Reference Only

If the question intended to ask about pirtobrutinib instead:

Approved Indications

• Relapsed/refractory mantle cell lymphoma (MCL) after ≥2 prior lines including a BTK inhibitor 2, 3
• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in various settings 4, 5

Dosing

• 200 mg orally once daily until progression or unacceptable toxicity 3, 6, 7

Clinical Context

Pirtobrutinib is a noncovalent BTK inhibitor recommended by NCCN as second-line or subsequent therapy for MCL patients with progressive disease on prior covalent BTK inhibitors 2. In the BRUIN trial, it demonstrated 50-58% overall response rate in heavily pretreated MCL patients 3, 7.