Leukemias, lymphomas, and other hematologic cancers:

Indications for: KYPROLIS

In combination with dexamethasone, or lenalidomide plus dexamethasone, or daratumumab 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.

Adult Dosage:

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. Dexamethasone combination: 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 subsequent cycles. 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 subsequent cycles. Lenalidomide/dexamethasone combination: 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 subsequent cycles. From Cycle 13, omit the Day 8 and 9 doses. Discontinue carfilzomib after Cycle 18. Refer to full labeling for lenalidomide and dexamethasone dosing. Daratumumab/dexamethasone combination: 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 subsequent cycles. 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 subsequent cycles. Refer to full labeling for daratumumab and dexamethasone dosing. Monotherapy: 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 27mg/m2 on Day 8 (by 10-min infusion regimen) or 56mg/m2 on Day 8 (by 30-min infusion regimen) and continue same dose for subsequent cycles. From Cycle 13, omit the Day 8 and 9 doses. 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.

Children Dosage:

Not established.

KYPROLIS Warnings/Precautions:

Monitor for signs/symptoms of 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).

KYPROLIS Classification:

Proteasome inhibitor.

KYPROLIS Interactions:

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.

Adverse Reactions:

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:

NO

How Supplied:

Single-use vial—1