polatuzumab vedotin

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
pol-a-tooz-ue-mab ve-doe-tin


Trade Name(s)

  • Polivy

Ther. Class.

antineoplastics

Pharm. Class.

monoclonal antibodies

Indications

  • 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).

Action

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 Effect(s):

  • 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.

Pharmacokinetics

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)

ROUTEONSETPEAKDURATION
IVunknownunknownunknown

Contraindication/Precautions

Contraindicated in:

  • Moderate or severe hepatic impairment;
  • OB:   Pregnancy;
  • Lactation:  Lactation.

Use Cautiously in:

  • 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: ↓ appetite, ↑ amylase, ↑ lipase, ↑ liver enzymes, diarrhea, hypoalbuminemia, vomiting, weight loss, HEPATOTOXICITY, hyperbilirubinemia

GU: ↑ serum creatinine, ↓ fertility (men)

Hemat: ANEMIA, lymphopenia, NEUTROPENIA, THROMBOCYTOPENIA

MS: arthralgia

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

Resp: dyspnea

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

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

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.

Route/Dosage

IV (Adults): 1.8 mg/kg every 21 days for 6 cycles.

Availability

Lyophilized powder for injection: 30 mg/vial, 140 mg/vial

Assessment

  • Monitor for signs/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 polatuzumab vedotin 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, ↓ by one dose level.  If Grade 3 peripheral sensory neuropathy occurs,  hold polatuzumab vedotin until Grade ≤2 and ↓ by one dose level.  If Grade 4 peripheral neuropathy occurs,  permanently discontinue polatuzumab vedotin.  If Grade 2–3 peripheral motor neuropathy occurs,  hold polatuzumab vedotin until Grade ≤1 and ↓ by one dose level.  If Grade 4 peripheral motor neuropathy occurs,  permanently discontinue polatuzumab vedotin.  For patients receiving polatuzumab vedotin with bendamustine and rituximab:  If Grade 2–3 peripheral neuropathy occurs,  hold polatuzumab vedotin until Grade ≤1. If recovered to Grade ≤1 before Day 14, restart next cycle at permanently ↓ dose of 1.4 mg/kg. If prior dose ↓ to 1.4 mg/kg already occurred, discontinue polatuzumab vedotin. If not recovered to Grade ≤1 before Day 14, discontinue polatuzumab vedotin.  If Grade 4 peripheral neuropathy occurs,  discontinue polatuzumab vedotin.
  • Monitor for signs/symptoms of infusion-related reactions (fever, chills, sweating, myalgia, headache, dizziness, nausea, vomiting, urticaria, pruritus, shortness of breath, wheezing) during and within 24 hr of 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 polatuzumab vedotin. For recurrent Grade 2 wheezing or urticaria or for recurrence of any Grade 3 symptoms, permanently discontinue polatuzumab vedotin. If symptoms completely resolve, resume infusion at 50% of rate achieved before interruption. If no infusion related symptoms occur, ↑ 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 polatuzumab vedotin.
  • Monitor for signs/symptoms of infection (fever, chills, sore throat, cough, dyspnea, skin lesions) during therapy.
  • Monitor for signs/symptoms of PML (new or worsening neurological, cognitive, or behavioral changes; progressive weakness; hemianopia; diplopia; other visual field defects; aphasia; loss of coordination), an opportunistic infection of the brain caused by the JC virus, which may be fatal.  If PML is suspected,  hold polatuzumab vedotin and any concurrent chemotherapy.  If PML diagnosis confirmed,  discontinue permanently polatuzumab vedotin.
  • Assess for signs/symptoms of tumor lysis syndrome (malaise, tachycardia, hypotension, confusion, delirium, arthralgia, myalgia, muscle spasms or twitches, paresthesia, headache, dizziness, nausea, vomiting, dark urine, acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, hypophosphatemia) in patients with advanced stage disease and/or with ↑ tumor burden; may be fatal. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.
  • Monitor for signs/symptoms of hepatotoxicity (fatigue, nausea, upper abdominal pain, jaundice, scleral icterus, dark urine, clay-colored stools).

Lab Test Considerations:

Verify 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 polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone; consider prophylactic use of G-CSF therapy in patients receiving polatuzumab vedotin with bendamustine and rituximab.  For patients receiving polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone:  If Grade 3–4 neutropenia occurs,  hold all therapy until ANC recovers to >1000 cells/mcL. If ANC recovers to >1000 cells/mcL on or before Day 7, resume all therapy without dose ↓. Consider G-CSF prophylaxis for subsequent cycles, if not previously given. If ANC recovers to >1000 cells/mcL after Day 7, restart all therapy. Consider G-CSF prophylaxis for subsequent cycles, if not previously given. If prophylaxis was given, consider dose ↓ of polatuzumab vedotin.  For patients receiving polatuzumab vedotin with bendamustine and rituximab:  If Grade 3–4 neutropenia occurs,  hold all therapy until ANC recovers to >1000 cells/mcL. If ANC recovers to >1000 cells/mcL on or before Day 7, resume all therapy without dose ↓. Consider G-CSF prophylaxis for subsequent cycles, if not previously given. If ANC recovers to >1000 cells/mcL after Day 7, restart all therapy. Consider G-CSF prophylaxis for subsequent cycles, if not previously given. If prophylaxis was given, consider dose ↓ of bendamustine. If dose ↓ of bendamustine has already occurred, consider dose ↓ of polatuzumab vedotin to 1.4 mg/kg.
  •  For patients receiving polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone:  If Grade 3–4 thrombocytopenia occurs,  hold all therapy until platelets recover to >75,000 cells/mcL. If platelets recover to >75,000 cells/mcL on or before Day 7, resume all therapy without dose ↓. If platelets recover to >75,000 cells/mcL after Day 7, restart all therapy, and consider dose ↓ of polatuzumab vedotin.  For patients receiving polatuzumab vedotin with bendamustine and rituximab:  If Grade 3–4 thrombocytopenia occurs,  hold all therapy until platelets recover to >75,000 cells/mcL. If platelets recover to >75,000 cells/mcL on or before Day 7, resume all therapy without dose ↓. If platelets recover to >75,000 cells/mcL after Day 7, restart all therapy, with dose ↓ of bendamustine. If dose ↓ of bendamustine already occurred, consider dose ↓ of polatuzumab vedotin to 1.4 mg/kg.
  • Monitor AST, ALT, and total bilirubin periodically during therapy.

Implementation

  • Dose reduction schedule  Starting dose:  1.8 mg/kg 1st dose ↓:  1.4 mg/kg 2nd dose ↓:  1 mg/kg Requirement for further dose ↓:  Discontinue polatuzumab vedotin.
  • Administered with bendamustine and rituximab in any order.
  • Premedicate with antihistamine and antipyretic 30–60 min prior to polatuzumab vedotin.
  • 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

  • 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 2nd practitioner independently double-check original order, calculations, and infusion pump settings.
  • IV Use double gloves and a protective gown to prepare and administer. If possible, prepare in a biological safety cabinet; eye, face, and respiratory protection may be needed. Prepare and administer in a closed-system drug transfer device. During administration, if there is a potential that the substance could splash or if the patient may resist, use eye and face protection. Discard IV equipment in specially designated containers. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water.
  • Intermittent Infusion:   Reconstitution: 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. 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.  Concentration:  20 mg/mL. Dilution:  Dilute with ≥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. 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 administer other drugs through same IV line.

Patient/Family Teaching

  • Explain purpose and side effects of  Polivy. Do not stop receiving drug without consulting health care provider. If an appointment is missed, contact health care provider as soon as possible to reschedule. Advise patient to read  Medication Guide  before starting and periodically during therapy in case of changes.
  • Caution patient to notify health care provider 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 (fatigue, nausea, upper abdominal pain, yellowing of skin or eyes, dark urine, light-colored stools) 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 provider 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 provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
  • Rep:  May cause fetal harm. Advise women of reproductive potential to use effective contraception during and for ≥3 mo after last dose and to avoid breastfeeding for ≥2 mo after last dose. Advise men with female partners of reproductive potential to use effective contraception during and for ≥5 mo after last dose. May impair male fertility.

Evaluation/Desired Outcomes

  • 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.