polatuzumab vedotin

POL-a-TOOZ-ue-mab ve-DOE-tin

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies

High Alert

Previously untreated diffuse large B-cell lymphoma, not otherwise specified, or high-grade B-cell lymphoma in patients who have an International Prognostic Index score ≥2 (in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone).
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.

Therapeutic effects:

Improved progression-free survival of previously untreated diffuse large B-cell lymphoma or high-grade B-cell lymphoma.
Decreased progression of relapsed or refractory diffuse large B-cell lymphoma.

Absorption: IV administration results in complete bioavailability.

Distribution: Not widely distributed to tissues.

Metabolism/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.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraindicated in:

Moderate or severe hepatic impairment;
OB: Pregnancy;
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.

F and E: hypocalcemia, hypokalemia, hypophosphatemia

GI: diarrhea, hypoalbuminemia, ↑amylase, ↑lipase, ↑liver enzymes, vomiting, HEPATOTOXICITY, hyperbilirubinemia

GU: ↑serum creatinine, ↓fertility (males)

Hemat: anemia, lymphopenia, neutropenia, thrombocytopenia

Metab: ↓appetite, ↓weight

MS: arthralgia

Neuro: dizziness, fatigue, peripheral neuropathy, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

Resp: dyspnea

Misc: fever, infection, infusion reactions, tumor lysis syndrome

Drug-drug:

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: 30 mg/vial; 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. For patients receiving Polivy with rituximab, cyclophosphamide, doxorubicin, and prednisone: If Grade 2 peripheral sensory neuropathy occurs, if recovered to ≤Grade 1 before next dose, resume at same dose level. If Grade 2 continues at time of next dose, reduce one dose level. If Grade 3 peripheral sensory neuropathy occurs,hold Polivy until ≤Grade 2 and reduce one dose level. If Grade 4 peripheral neuropathy occurs, permanently discontinue Polivy. If Grade 2–3 peripheral motor neuropathy occurs, hold Polivy until ≤Grade 1 and reduce one dose level. If Grade 4 peripheral motor neuropathy occurs, permanently discontinue Polivy.
For patients receiving Polivy with bendamustine and rituximab
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 min. 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 JC virus, which 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. Administer prophylactic granulocyte colony-stimulating factor (G-CSF) therapy for neutropenia in patients receiving Polivywith rituximab, cyclophosphamide, doxorubicin, and prednisone; consider prophylactic use of G-CSF therapy in patients receiving Polivy with bendamustine and rituximab. For patients receiving Polivy with rituximab, cyclophosphamide, doxorubicin, and prednisone: 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 G-CSF prophylaxis for subsequent cycles, if not previously given. If ANC recovers to >1000/microliter after Day 7, restart all therapy. Consider G-CSF prophylaxis for subsequent cycles, if not previously given. If prophylaxis was given, consider dose reduction of Polivy.
  For patients receiving Polivy with bendamustine and rituximab
  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.
- For patients receiving polatuzumab with rituximab, cyclophosphamide, doxorubicin, and prednisone
  If Grade 3–4 thrombocytopenia occurs, hold all therapy until platelets recover to >75,000/microliter. If platelets recover to >75,000/microliter on or before Day 7, resume all therapy without dose reductions. If platelets recover to >75,000/microliter after Day 7, restart all therapy, and consider dose reduction of Polivy.
  For patients receiving polatuzumab with bendamustine and rituximab
  If Grade 3–4 thrombocytopenia occurs, hold all therapy until platelets recover to >75,000/microliter. If platelets recover to >75,000/microliter on or before Day 7, resume all therapy without dose reductions. If platelets recover to >75,000/microliter 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.

Dose reduction schedule: Starting dose: 1.8 mg/kg; First dose reduction: 1.4 mg/kg; Second dose reduction: 1 mg/kg; Requirement for further dose reduction: discontinue therapy.
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.

IV Administration:

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 1.8 mL or 7.2 mL of sterile water for injection into 30 mg or 140 mg vial of polatuzumab respectively, 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. Diluent: 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 the initial dose over 90 min. Monitor patients for infusion-related reactions during the infusion and for ≥90 min following completion of the infusion. If the previous infusion was well tolerated, the subsequent dose may be infused over 30 min and patients should be monitored during the infusion and for ≥30 min after completion of the infusion. Infuse using a dedicated infusion line with a sterile, nonpyrogenic, low-protein binding in-line or add-on filter (0.2- or 0.22-micron pore size) and catheter.
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 cause fetal harm. 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.

Improved progression free survival of previously untreated diffuse large B-cell lymphoma or high-grade B-cell lymphoma.
Decreased progression of relapsed or refractory diffuse large B-cell lymphoma.

Polivy

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