Leukemias, lymphomas, and other hematologic cancers:
Indications for: KYPROLIS
In combination with dexamethasone, or lenalidomide plus dexamethasone, or daratumumab plus dexamethasone, or daratumumab plus hyaluronidase-fihj plus dexamethasone, or isatuximab plus dexamethasone, for the treatment of patients with relapsed or refractory multiple myeloma who have received 1–3 lines of therapy. As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received ≥1 lines of therapy.
See full labeling. Hydrate prior to and following administration as needed. Premedicate with dexamethasone prior to all Cycle 1 doses, during subsequent cycles, and if infusion-related reactions occur. In combination with dexamethasone, daratumumab/dexamethasone, daratumumab/hyaluronidase-fihj/dexamethasone: infuse over 30mins. Once weekly regimen: give once weekly for 3 weeks (Days 1, 8, 15), followed by a 13-day rest period (Days 16–28). In Cycle 1: initially 20mg/m2 per dose on Day 1; if tolerated increase to 70mg/m2 on Day 8 and thereafter. As monotherapy or in combination with dexamethasone, daratumumab/dexamethasone, daratumumab/hyaluronidase-fihj/dexamethasone, or isatuximab/dexamethasone: infuse over 30mins. Twice weekly regimen: give on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17–28). In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 56mg/m2 on Day 8 and thereafter. If given as monotherapy: carfilzomib may be omitted on Days 8 and 9 of Cycle 13 onward. Refer to full labeling for daratumumab, dexamethasone, daratumumab and hyaluronidase-fihj, isatuximab dosing. As monotherapy or in combination with lenalidomide/dexamethasone: infuse over 10mins on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17–28). In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 27mg/m2 on Day 8 and thereafter. From Cycle 13, omit the Day 8 and 9 doses. When combined with lenalidomide/dexamethasone, discontinue carfilzomib after Cycle 18. Refer to full labeling for lenalidomide and dexamethasone dosing. All: continue until disease progression or unacceptable toxicity occurs. Mild or moderate hepatic impairment: reduce dose by 25%. ESRD on dialysis: give dose after session. Dose modifications for toxicity: see full labeling.
Monitor for cardiac failure or ischemia; evaluate promptly if toxicity is suspected. Increased risk of cardiac complications in patients with NYHA Class III and IV heart failure, recent MI, conduction abnormalities, angina, uncontrolled arrhythmias; do full medical assessment prior to starting. Withhold therapy if pulmonary hypertension occurs until resolved; consider restarting after reevaluation. Discontinue if pulmonary toxicity occurs. Monitor for tumor lysis syndrome (TLS); interrupt therapy and manage promptly if occurs. Interrupt for Grade 3 or 4 dyspnea until resolved; consider restarting after reevaluation. Maintain adequate hydration. Monitor for volume overload. Evaluate signs/symptoms of blood loss; reduce or withhold dose as appropriate. Monitor for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); discontinue and evaluate if suspected. Consider progressive multifocal leukoencephalopathy (PML) if new onset or changes in preexisting neurological signs/symptoms. Discontinue and evaluate if posterior reversible encephalopathy syndrome (PRES) or PML is suspected. Optimize BP prior to initiation; withhold and evaluate if uncontrolled. Monitor BP, platelets, renal function, liver enzymes, electrolytes (eg, potassium) regularly; reduce or withhold dose as appropriate. Hepatic impairment. Give thromboprophylaxis for combination therapy. Consider antiviral prophylaxis to prevent herpes zoster reactivation. Elderly. Embryo-fetal toxicity. Advise to use effective contraception during and for ≥6 months (females of reproductive potential) or ≥3 months (males w. female partners) after last dose. Pregnancy: avoid; exclude status prior to initiation. Nursing mothers: not recommended (during and for 2 weeks after last dose).
Increased risk of thrombosis with oral or hormonal contraception; consider non-hormonal alternatives during combination therapy. Increased fatal/serious toxicities in combination with melphalan + prednisone in newly diagnosed transplant-ineligible patients.
Anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, hypertension, pyrexia, insomnia, muscle spasm, cough, upper RTI, hypokalemia, nausea, headache, peripheral edema; cardiotoxicity, pulmonary HTN, acute renal failure (may be fatal), infusion-related reactions, hemorrhage, TLS, hepatic toxicity/failure, TTP/HUS, PRES, PML.
Generic Drug Availability: