Relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after ≥2 prior therapies (in combination with bendamustine and rituximab).
Binds to the CD79b antigen on the surface of B cells, releasing monomethylauristatin E (MMAE). MMAE binds to microtubules and kills dividing cells by inhibiting cell division and inducing apoptosis.
Decreased progression of diffuse large B-cell lymphoma.
Absorption: IV administration results in complete bioavailability.
Distribution: Not widely distributed to tissues.
Metabolism and Excretion: Broken down into small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites.
Half-life: Antibody-conjugated MMAE– 12 days; Unconjugated MMAE– 4 days.
TIME/ACTION PROFILE (plasma concentrations)
- Moderate or severe hepatic impairment
- OB: Pregnancy (may cause fetal harm);
- Lactation: Lactation.
Use Cautiously in:
- Patients with pre-existing peripheral neuropathy
- Rep: Women of reproductive potential and men with female partners of reproductive potential
- Pedi: Safety and effectiveness not established in children.
Adverse Reactions/Side Effects
F and E: hypocalcemia, hypokalemia, hypophosphatemia
GI: HEPATOTOXICITY, diarrhea, hypoalbuminemia, ↑ amylase, ↑ lipase, ↑ liver enzymes, vomiting, hyperbilirubinemia
GU: ↑ serum creatinine, ↓ fertility (males)
Hemat: ANEMIA, NEUTROPENIA, THROMBOCYTOPENIA, lymphopenia
Metabolic: ↓ appetite, ↓ weight
Neuro: peripheral neuropathy, PROGRESSION MULTIFOCAL LEUKOENCEPHALOPATHY (PML), dizziness, fatigue
Resp: dyspnea, pneumonia, upper respiratory tract infection
Misc: INFECTION, fever, infusion reactions, tumor lysis syndrome
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Strong CYP3A inhibitors, including ketoconazole , may ↑ unconjugated MMAE levels and risk of toxicity.
- Strong CYP3A inducers, including rifampin , may ↓ unconjugated MMAE levels and effectiveness.
IV (Adults): 1.8 mg/kg every 21 days for 6 cycles.
Lyophilized powder for injection: 140 mg/vial
- Monitor for signs and symptoms of peripheral neuropathy (hypoesthesia, hyperesthesia, paresthesia, dysesthesia, neuropathic pain, burning sensation, weakness, gait disturbance) during therapy. May occur as early as 1st cycle and effects are cumulative. If Grade 2–3 peripheral neuropathy occurs, hold Polivy until ≤Grade 1. If recovered to ≤Grade 1 before Day 14, restart next cycle at permanently reduced dose of 1.4 mg/kg. If prior dose reduction to 1.4 mg/kg, discontinue therapy. If not recovered to ≤Grade 1 before Day 14, discontinue therapy. If Grade 4 peripheral neuropathy occurs, discontinue Polivy.
- Monitor for signs and symptoms of infusion-related reactions (fever, chills, flushing, dyspnea, hypotension, urticaria) during and after infusion; may occur as late as 24 hr after infusion. If Grade 1–3 infusion-related reactions occur, hold infusion and give supportive treatment. For 1st 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. If symptoms completely resolve, resume infusion at 50% of rate achieved before interruption. If no infusion related symptoms occur, escalate rate of infusion in increments of 50 mg/hr every 30 min. For next cycle, infuse over 90 minutes. If no infusion-related reaction occurs, infuse subsequent infusions over 30 min. Administer premedication for all cycles. If Grade 4 infusion-related reactions occur, immediately stop infusion. Give supportive treatment. Permanently discontinue Polivy.
- Monitor for signs and symptoms of infection (fever, chills, sore throat, cough, dyspnea, skin lesions) during therapy. Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus.
- Monitor for signs and symptoms of PML, an opportunistic infection of the brain caused by the Jakob Cruzfeldt (JC) virus, that may be fatal (new or worsening neurological, cognitive, or behavioral changes) during. Hold Polivy and any concomitant chemotherapy if PML is suspected; discontinue permanently if diagnosis confirmed.
- Monitor for signs and symptoms of tumor lysis syndrome due to rapid reduction in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hypophosphatemia) during therapy. Risks are higher in patients with greater tumor burden; may be fatal. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.
Lab Test Considerations:
Obtain a negative pregnancy test before starting therapy.
- Monitor CBC during therapy. May cause neutropenia, thrombocytopenia, and anemia. Consider prophylactic use of granulocyte colony stimulating factor. If Grade 3–4 neutropenia occurs, hold all therapy until ANC recovers to >1000/microliter. If ANC recovers to >1000/microliter on or before Day 7, resume all therapy without dose reductions. Consider granulocyte colony stimulating factor prophylaxis for subsequent cycles, if not previously given. If ANC recovers to >1000/microliter after Day 7, restart all therapy. Consider granulocyte colony stimulating factor 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.
- If Grade 3–4 thrombocytopenia occurs, hold all therapy until platelets recover to >75,000/3 . If platelets recover to >75,000/3 on or before Day 7, resume all therapy without dose reductions. If platelets recover to >75,000/mm3 after Day 7, restart all therapy, with dose reduction of bendamustine. If dose reduction of bendamustine already occurred, consider dose reduction of Polivy to 1.4 mg/kg.
- Monitor AST, ALT, and total bilirubin periodically during therapy.
- Risk for peripheral neurovascular dysfunction (Adverse Reaction)
- Risk for infection (Adverse Reaction)
- Administered with bendamustine and rituximab in any order.
- Premedicate with an antihistamine and antipyretic 30–60 min prior Polivy.
- Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus during therapy.
- If a dose is missed, administer as soon as possible. Adjust schedule to maintain a 21-day interval between doses.
- High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.
- IV Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers.
- Intermittent Infusion: Reconstitute each vial by slowly injecting 7.2 mL of Sterile Water for Injection toward wall of vial for a concentration of 20 mg/mL. Swirl gently; do not shake. Solution is colorless to slightly brown, clear to slightly opalescent; do not administer solutions that are cloudy, discolored, or contain particulate matter. Reconstituted solution is stable up to 48 hr if refrigerated or 8 hr at room temperature; do not freeze or expose to direct sunlight. Dilution: Dilute with at least 50 mL of 0.9% NaCl, 0.45% NaCl, or D5W. Concentration: 0.72–2.7 mg/mL. Gently invert to mix; do not shake. If diluted with 0.9% NaCl, solution is stable for up to 4 hr at room temperature or up to 24 hr if refrigerated. If diluted with 0.45% NaCl, solution is stable for up to 4 hr at room temperature or up to 18 hr if refrigerated. If diluted with D5W, solution is stable for up to 6 hr at room temperature or up to 36 hr if refrigerated.
- Rate: Infuse over 90 min using a dedicated infusion line with a sterile, non-pyrogenic, low-protein binding in-line or add-on filter (0.2- or 0.22-micron pore size) and catheter. If infusion well tolerated, infuse subsequent doses over 30 min.
- Y-Site Incompatibility: Do not mix with or infuse with other drugs in same line.
- Explain purpose of Polivy to patient.
- Caution patient to notify health care professional immediately if signs and symptoms of bleeding, infection (≥fever of 38°C (100.4°F), chills, cough, pain on urination), PML (confusion, dizziness, loss of balance; difficulty talking or walking; changes in vision), tumor lysis syndrome (nausea, vomiting, diarrhea, lethargy) or hepatotoxicity (nausea, vomiting, diarrhea, lethargy) occur. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should also be cautioned not to drink alcoholic beverages or to take products containing aspirin or NSAIDs; may precipitate GI hemorrhage.
- Advise patient to notify health care professional if signs and symptoms of peripheral neuropathy (numbness or tingling of hands or feet, muscle weakness) or infusion-related reactions (fever, chills, rash, breathing problems within 24 hr of infusion) occur.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Rep: May be teratogenic. Advise females of reproductive potential to use effective contraception during and for at least 3 mo after last dose and to avoid breastfeeding for at least 2 mo after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for at least 5 mo after last dose. May impair male fertility.
Decreased progression of diffuse large B-cell lymphoma.