Product Review

Criteria for Use Updates for Enzalutamide, Daratumumab, Elotuzumab, Carfilzomib, and Ixazomib


 

CARFILZOMIB (KYPROLIS) Criteria for Use, December 2016

Exclusion Criteria: If the answer to ANY item below is met, then the patient should NOT receive carfilzomib.

  • Care for the oncologic disease being treated not provided by a VA or VA purchased care (eg, Choice Program, Fee Basis) oncology provider
  • Patient is noncompliant with medication, follow-up, or laboratory appointments
  • Hemoglobin < 8 g/dL; Must transfuse to hemoglobin above 8 g/dL prior to therapy initiation
  • Absolute neutrophil count (ANC) < 1,000/mm 3
  • Platelet count < 50,000/mm 3 (< 30,000/mm 3 if myeloma involvement in bone marrow > 50%)
  • ECOG Performance Status > 2
  • Total bilirubin > 1.5 x the upper limit of the normal range or ALT and AST > 3 x ULN
  • NYHA Class III and IV heart failure (refer to Issues for Consideration; those at risk for cardiac failure and ischemia were also excluded from clinical trials)
  • LVEF < 40%
  • Uncontrolled hypertension
  • Grade 3 or 4 peripheral neuropathy
  • Ongoing or active systemic infection, including active hepatitis B or C, or known HIV

Issues for Consideration

  • A significant percentage of patients on carfilzomib develop dyspnea. This drug should be used with caution in patients with underlying lung disease. Close monitoring for worsening of dyspnea is advised.
  • Risk of cardiac failure increases in those aged > 75 years; those with NYHA Class III and IV heart failure, recent MI, conduction abnormalities, angina or arrhythmias uncontrolled by medications, were not eligible for clinical trials and may be at greater risk of cardiac complications. Refer to Prescribing Information for management recommendations.
  • Those aged > 75 years experienced greater toxicity than their younger counterparts.
  • Patients on dialysis: administer carfilzomib after the dialysis procedure.
  • Phase III evidence in heavily pretreated relapsed/refractory patients (median 5 prior regimens) of carfilzomib vs low-dose steroids ± cyclophosphamide indicates that the median overall survival is not significantly different between these treatment arms.

IXAZOMIB (NILARO) Criteria for Use, December 2016

Exclusion Criteria: If the answer to ANY item below is met, then the patient should NOT receive ixazomib

  • Care for the oncologic disease being treated not provided by a VA or VA purchased care (eg, Choice Program, Fee Basis) oncology provider
  • Patient is not a candidate for lenalidomide or dexamethasone therapy
  • Patient is refractory to lenalidomide or proteasomeinhibitor therapy (defined as disease progression while on treatment or within 60 days of last dose)
  • Absolute neutrophil count (ANC) < 1,000/mm 3
  • Platelet count < 75,000/mm 3
  • ECOG Performance Status > 2
  • Patient with CNS involvement
  • Patient receiving concurrent therapy with a strong CYP3A inducer (ie, rifampin, phenytoin, carbamazepine) that cannot be discontinued
  • Uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina or myocardial infarction within 6 months prior to start
  • Ongoing or active systemic infection, including active hepatitis B, hepatitis C, or known HIV

Issues for Consideration

  • Indirect comparisons of phase 3 data (KRd vs Rd and IRd vs Rd) show that in similar populations of pretreated relapsed, refractory myeloma patients, those receiving KRd experienced longer PFS (26.3 vs 21 months), greater CR (32% vs 12%), greater ORR (87% vs 78%) and longer duration of response (28.6 vs 20.5 months). Therefore, providers may want to consider using carfilzomib in those meeting its criteria for use.
  • Ixazomib is cytotoxic. Capsules should not be opened or crushed. Waste should be considered hazardous.
  • Avoid concomitant use of strong CYP3A inducers (rifampin, phenytoin, carbamazepine, and St. John’s Wort).

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