Active Ingredient: Duvelisib
Duvelisib monotherapy is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) after at least two prior therapies.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 25 milligrams duvelisib, 2 times daily.
The recommended dose is 25 mg duvelisib twice daily. A cycle consists of 28 days. Treatment should be continued until disease progression or unacceptable toxicity.
Patients should be advised that if a dose is missed by less than 6 hours, the missed dose should be taken right away and the next dose should be taken as usual. If a dose is missed by more than 6 hours, patients should be advised to wait and to take the next dose at the usual time.
Toxicities should be managed as per the following table with dose reduction, treatment hold, or discontinuation of duvelisib.
Duvelisib dose modifications and toxicity management:
| Toxicity | Adverse reaction grade | Recommended management |
|---|---|---|
| Nonhematologic adverse reactions | ||
| Infections | Grade 3 or higher infection | • Withhold duvelisib until resolved • Resume at the same or reduced dose (25 mg or 15 mg twice daily) |
| Clinical CMV infection or viremia (positive PCR or antigen test) | • Withhold duvelisib until resolved • Resume at the same or reduced dose (25 mg or 15 mg twice daily) • If duvelisib is resumed, monitor patients for CMV reactivation (by PCR or antigen test) at least monthly. In clinical studies iNHL, FL (IPI-145-06) and CLL/SLL (IPI-145-07 the outcome of starting at same dose or reduction are comparable | |
| PJP | • For suspected PJP, withhold duvelisib until evaluated • For confirmed PJP, discontinue duvelisib | |
| Non-infectious diarrhoea or colitis | Mild/moderate diarrhoea (Grade 1-2, up to 6 stools per day over baseline) and responsive to anti- diarrhoeal agents, OR Asymptomatic (Grade 1) colitis | • No change in dose • Initiate supportive therapy with anti-diarrhoeal agents as appropriate • Monitor at least weekly until resolved |
| Mild/moderate diarrhoea (Grade 1-2, up to 6 stools per day over baseline) and unresponsive to anti-diarrhoeal agents | • Withhold duvelisib until resolved • Initiate supportive therapy with enteric acting steroids (e.g., budesonide) • Monitor at least weekly until resolved • Resume at a reduced dose (15 mg twice daily) | |
| Abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, OR Severe diarrhoea (Grade 3, >6 stools per day over baseline) | • Withhold duvelisib until resolved • Initiate supportive therapy with enteric acting steroids (e.g., budesonide) or systemic steroids • Monitor at least weekly until resolved • Resume at a reduced dose (15 mg twice daily) • For recurrent Grade 3 diarrhoea or recurrent colitis of any grade, discontinue duvelisib | |
| Life-threatening | • Discontinue duvelisib | |
| Cutaneous reactions | Grade 1-2 | • No change in dose • Initiate supportive care with emollients, anti- histamines (for pruritus), or topical steroids • Monitor closely |
| Grade 3 | • Withhold duvelisib until resolved • Review all concomitant medications and discontinue any medication potentially contributing to the event • Initiate supportive care with steroids (topical or systemic) and antihistamines for pruritus • Monitor at least weekly until resolved • Resume at reduced dose (15 mg twice daily) • If severe cutaneous reaction does not improve, worsens, or recurs, discontinue duvelisib | |
| Life-threatening | • Discontinue duvelisib | |
| SJS, TEN, DRESS (any grade) | • Discontinue duvelisib for any grade | |
| Pneumonitis without suspected infectious cause | Moderate (Grade 2) symptomatic pneumonitis | • Withhold duvelisib • Treat with systemic steroid therapy • If pneumonitis recovers to Grade 0 or 1, duvelisib may be resumed at reduced dose (15 mg twice daily) • If non-infectious pneumonitis recurs or patient does not respond to steroid therapy, discontinue duvelisib |
| Severe (Grade 3) or life- threatening pneumonitis | • Discontinue duvelisib • Treat with systemic steroid therapy | |
| ALT/AST elevation | 3 to 5 × upper limit of normal (ULN) (Grade 2) | • Maintain duvelisib dose • Monitor at least weekly until return to < 3 × ULN |
| > 5 to 20 × ULN (Grade 3) | • Withhold duvelisib and monitor at least weekly until return to < 3 × ULN • Resume duvelisib at same dose (25 mg twice daily) for first occurrence or at a reduced dose (15 mg twice daily) for subsequent occurrence | |
| > 20 × ULN (Grade 4) | • Discontinue duvelisib | |
| Neutropenia | Absolute neutrophil count (ANC) 0.5 to 1.0 × 109/L | • Maintain duvelisib dose • Monitor ANC at least weekly |
| ANC less than 0.5 × 109/L | • Withhold duvelisib. • Monitor ANC until > 0.5 × 109/L • Resume duvelisib at same dose (25 mg twice daily) for first occurrence or at a reduced dose (15 mg twice daily) for subsequent occurrence | |
| Thrombocytopenia | Platelet count 25 to < 50 × 109/L (Grade 3) with Grade 1 bleeding | • No change in dose • Monitor platelet counts at least weekly |
| Platelet count 25 to < 50 × 109/L (Grade 3) with Grade 2 bleeding or Platelet count < 25 × 109/L (Grade 4) | • Withhold duvelisib • Monitor platelet counts until ≥ 25 × 109/L and resolution of bleeding (if applicable) • Resume duvelisib at the same dose (25 mg twice daily) for first occurrence or resume at a reduced dose (15 mg twice daily) for subsequent occurrence | |
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; CMV = cytomegalovirus; DRESS = drug reaction with eosinophilia and systemic systems; PCR = polymerase chain reaction; PJP = Pneumocystis jirovecii pneumonia; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal Note: Doses withheld for >42 days due to treatment-related toxicity will result in permanent discontinuation from treatment
Duvelisib can be taken with or without food.
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