Pirtobrutinib

JAYPIRCA

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What it isNoncovalent BTK inhibitor; relapsed or refractory mantle-cell lymphoma and chronic lymphocytic leukemia.

Why this oneBecause it does not depend on the C481 cysteine, it keeps working after the C481S mutation that defeats ibrutinib, acalabrutinib and zanubrutinib.

What limits itSerious infection, bleeding, cytopenias, atrial arrhythmia, and second malignancies require surveillance.

FDA-approved for

relapsed/refractory mantle cell lymphoma
relapsed/refractory chronic lymphocytic leukemia

FDA label

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FDA dosing	Population	Start	Target	Max
Mantle cell lymphoma, previously treated (prior BTK inhibitor)	adults	200 mg QD	200 mg QD until progression or unacceptable toxicity	200 mg QD
CLL/SLL, previously treated	adults	200 mg QD	200 mg QD until progression or unacceptable toxicity	200 mg QD

Renal Severe (eGFR 15–29): reduce 200→100 mg QD (otherwise reduce by 50 mg; discontinue if on 50 mg). Mild–moderate (eGFR 30–89): no adjustment

Hepatic No adjustment needed

Instructions

Swallow whole with water; do not cut, crush, or chew
With or without food; take at the same time each day
Missed dose >12 h: skip — take next dose as scheduled
Toxicity (Grade ≥3 non-heme, defined cytopenias): interrupt until recovery to Grade 1/baseline, restart 200→100→50 mg QD by occurrence; discontinue on 4th occurrence
If strong CYP3A inhibitor unavoidable: reduce dose by 50 mg (interrupt if on 50 mg); if moderate CYP3A inducer unavoidable: increase 200→300 mg (or +50 mg if on 50/100 mg)

Cautions

Fatal/serious infections incl. opportunistic (Grade ≥3 in 25%, most commonly pneumonia); consider vaccination/antimicrobial prophylaxis
Hemorrhage incl. fatal; consider withholding 3–7 days pre/post surgery
Cytopenias (Grade 3/4 neutropenia 27%) — monitor CBC regularly
Cardiac arrhythmias: atrial fibrillation/flutter (3.4%)
Second primary malignancies (9%) — advise sun protection
Hepatotoxicity incl. drug-induced liver injury — monitor bilirubin/transaminases; discontinue on confirmed DILI
Embryo-fetal toxicity — effective contraception during and 1 week after

Adverse reactions

Fatigue (31%)
Decreased neutrophils (54%), hemoglobin (43%), leukocytes (32%), platelets (31%), lymphocytes (31%), calcium (30%)
Musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, bruising (MCL ≥15%)

Pregnancy Can cause fetal harm (animal data at ~3x human exposure); verify pregnancy status before starting; advise of fetal risk

Lactation Do not breastfeed during treatment and for 1 week after last dose

NO BOXED WARNINGS