POLIVY dose modifications for peripheral neuropathy 1

Severity* Dose Modification
Grade 2-3 Hold POLIVY dosing until improvement to Grade 1 or lower.
If recovered to Grade 1 or lower on or before Day 14, restart POLIVY with the next cycle at a permanently reduced dose of 1.4 mg/kg.
If a prior dose reduction to 1.4 mg/kg has occurred, discontinue POLIVY.
If not recovered to Grade 1 or lower on or before Day 14, discontinue POLIVY.
Grade 4 Discontinue POLIVY.

POLIVY dose modifications for infusion-related reactions 1

Severity* Dose Modification
Grade 1-3 Interrupt POLIVY infusion and give supportive treatment.
For the first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, permanently discontinue POLIVY.
For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue POLIVY.
Otherwise, upon complete resolution of symptoms, infusion may be resumed at 50% of the rate achieved prior to interruption. In the absence of infusion-related symptoms, the rate of infusion may be escalated in increments of 50 mg/hour every 30 minutes.
For the next cycle, infuse POLIVY over 90 minutes. If no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles.
Grade 4 Stop POLIVY infusion immediately.
Give supportive treatment.
Permanently discontinue POLIVY.

POLIVY+BR dose modifications for myelosuppression 1

Severity* Dose Modification
Grade 3-4
neutropenia

Hold all treatment until ANC recovers to >1000/μL.
If ANC recovers to >1000/μL on or before Day 7, resume all treatment without any additional dose reductions. Consider G-CSF prophylaxis for subsequent cycles, if not previously given. 
If ANC recovers to >1000/μL after Day 7:

  • Restart all treatment. Consider G-CSF prophylaxis for subsequent cycles, if not previously given. If prophylaxis was given, consider dose reduction of bendamustine
  • If dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg
Grade 3-4
thrombocytopenia

Hold all treatment until platelets recover to >75,000/μL.
If platelets recover to >75,000/μL on or before Day 7, resume all treatment without any additional dose reductions.
If platelets recover to >75,000/μL after Day 7:

  • Restart all treatment, with a dose reduction of bendamustine
  • If a dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg 

*Severity grading is based on NCI CTCAE version 4. 9
Severity on Day 1 of any cycle.
If primary cause is due to lymphoma, the dose of bendamustine may not need to be reduced.
NCI CTCAE version 4 symptom severity grading is indicated as follows. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4: life-threatening consequences; urgent intervention indicated. 9
ANC=absolute neutrophil count; ADL=activities of daily living.