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

DARATUMUMAB (DARZALEX) Criteria for Use, January 2017

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

• Patient is noncompliant with medication, follow-up, or laboratory appointments
• Patient unable or unwilling to be observed an extended period of time that may be necessary for first infusion (refer to Issues for Consideration )
• Hemoglobin < 8 g/dL; Must transfuse to hemoglobin above 8 gm/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 > 3x the upper limit of the normal range (except for Gilbert syndrome: direct bilirubin 2x ULN) or ALT and AST > 3x ULN
• NYHA Class III or IV heart failure (refer to Issues for Consideration )
• Ongoing or active systemic infection, including active hepatitis B or C, or known HIV (refer to Issues for Consideration )
• Positive pregnancy test

Issues for Consideration

• Drug infusion time will be dependent upon patient tolerance and exposure to daratumumab. Median duration of the first infusion was ~ 7 hours in the SIRIUS trial, followed by infusion times of 4.2 and 3.4 hours, subsequently.
• Type and screen patients shortly prior to starting treatment. When the sample is provided to the blood bank, inform them that the patient will be receiving daratumumab.
• Those with NYHA Class III or 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.
• Patients with active hepatitis B, C, or HIV were excluded from clinical trials with daratumumab, therefore safety and efficacy data are unknown in these patient populations. The risk of infections was slightly higher in the daratumumab-treated arms of the comparative studies. Use of daratumumab should only be considered in those with well-controlled hepatitis B, hepatitis C, or HIV.

ELOTUZUMAB (EMPLICITI) Criteria for Use, January 2017

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

• Patient is noncompliant with medication, follow-up, or laboratory appointments
• Patient is not a candidate for lenalidomide therapy (ie, is lenalidomide-refractory or possesses contraindications to therapy)
• Patient is not a candidate for high-dose dexamethasone therapy
• Hemoglobin < 8 g/dL; Must transfuse to hemoglobin above 8 gm/dL prior to therapy initiation
• Absolute neutrophil count (ANC) < 1,000/mm ³
• Platelet count < 50,000/mm3 (< 30,000/mm ³ if myeloma involvement in bone marrow > 50%)
• ECOG Performance Status > 2
• Total bilirubin > 2x the upper limit of the normal range (except for Gilbert syndrome: direct bilirubin > 2 mg/dL) or ALT and AST > 3x ULN
• NYHA Class III or IV heart failure (refer to Issues for Consideration )
• Ongoing or active systemic infection, including active hepatitis B or hepatitis C, or known HIV (refer to Issues for Consideration )
• Positive pregnancy test
• Patient intends to breastfeed during therapy

Issues for Consideration

• Those with NYHA Class III or 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.
• Patients with active hepatitis B, hepatitis C, or HIV were excluded from clinical trials with elotuzumab, therefore safety and efficacy data are unknown in these patient populations. The risk of infections (OI, fungal, viral) was greater in the elotuzumab arm vs control arm of the comparative clinical trial. Use of elotuzumab should only be considered in those with well-controlled hepatitis B, hepatitis C, or HIV.
• Disappointing response rates as monotherapy in the relapsed/refractory setting suggest that elotuzumab should be given in combination with lenalidomide and dexamethasone.
• Impact of elotuzumab/lenalidomide/dexamethasone on overall survival is not known as these data were not mature at the time ELOQUENT-2 was published.