Leukemias, lymphomas, and other hematologic cancers:

Indications for: GAZYVA

In combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). In combination with bendamustine followed by Gazyva monotherapy, for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximab-containing regimen. In combination with chemotherapy followed by Gazyva monotherapy, for the treatment of previously untreated stage II bulky, III or IV follicular lymphoma in patients achieving at least a partial remission.

Adult Dosage:

See full labeling. Premedicate (eg, glucocorticoid, APAP, antihistamine) before each infusion. Provide prophylactic hydration and antihyperuricemics to those at risk for TLS. Give by IV infusion for 6 treatment cycles (28 days duration). CLL: Cycle 1 (Day 1): 100mg at 25mg/hr over 4 hours; (Day 2): 900mg at 50mg/hr if no infusion-related reaction (IRR) occurred previously, and can be increased at 50mg/hr every 30mins to max 400mg/hr; if an IRR occurred, give at 25mg/hr and can be increased up to 50mg/hr every 30mins to max 400mg/hr; (Days 8 and 15): 1000mg at 100mg/hr if no IRR occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; if an IRR occurred, give at 50mg/hr and can be increased at 50mg/hr every 30mins to max 400mg/hr. Cycles 2–6 (Day 1): 1000mg at 100mg/hr if no IRR occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; if an IRR occurred, give at 50mg/hr and can be increased at 50mg/hr every 30mins to max 400mg/hr. FL: Relapsed/refractory: give with bendamustine for six 28-day cycles; Previously untreated: give with either bendamustine for six 28-day cycles, with CVP for eight 21-day cycles, or with CHOP for six 21-day cycles followed by two additional 21-day cycles of Gayva monotherapy. Cycle 1 (Day 1): 1000mg at 50mg/hr, can be increased at 50mg/hr every 30mins to max 400mg/hr; (Days 8 and 15): 1000mg at 100mg/hr if no IRR (or a Grade 1 IRR) occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; if Grade ≥2 IRR occurred previously, give at 50mg/hr and can be increased at 50mg/hr every 30mins to max 400mg/hr. Cycles 2–6 or 2–8 (Day 1): 1000mg at 100mg/hr if no IRR (or a Grade 1 IRR) occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; if Grade ≥2 IRR occurred previously, give at 50mg/hr and can be increased at 50mg/hr every 30mins to max 400mg/hr; followed by Gazyva monotherapy (every 2months for up to 2yrs): 1000mg at 100mg/hr if no IRR (or a Grade 1 IRR) occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; if Grade ≥2 IRR occurred previously, give at 50mg/hr and can be increased at 50mg/hr every 30mins to max 400mg/hr. In FL patients (if no Grade ≥3 IRR during Cycle 1, may administer Gazyva as a shorter, approx. 90min infusion from Cycle 2 onwards): 100mg/hr for 30mins, then 900mg/hr for approx. 60mins; if Grade 1–2 IRR with ongoing symptoms or Grade ≥3 IRR occurs during previous 90min infusion, administer all subsequent infusions at standard infusion rate. Management of infusion reactions, premedication: see full labeling.

Children Dosage:

Not established.

Boxed Warning:

Hepatitis B virus (HBV) reactivation. Progressive multifocal leukoencephalopathy (PML).

GAZYVA Warnings/Precautions:

Risk of hepatitis B virus (HBV) reactivation; immediately discontinue and any concomitant chemotherapy if occurs. Screen for HBV infection prior to initiation; if positive evidence, monitor and consider antiviral therapy. Discontinue treatment and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressives if progressive multifocal leukoencephalopathy (PML) develops. Monitor closely for infusion-related reactions; reduce infusion rate, interrupt, or permanently discontinue based on severity. Preexisting cardiac or pulmonary conditions: monitor more frequently during and post-infusion period for severe reactions. Risk of TLS in high tumor burden, high circulating lymphocyte count (>25 x 109/L), or renal impairment. Active infection: do not administer. History of recurring or chronic infections. Risk of neutropenia; monitor for signs of infection. Severe or prolonged neutropenia, give antimicrobial prophylaxis until resolved to Grade 1 or 2; consider antiviral and antifungal prophylaxis. Monitor for thrombocytopenia and hemorrhagic events esp. during the 1st cycle and if clinically indicated; if Grade 3 or 4 thrombocytopenia, obtain platelet counts more frequently until resolved; transfusion of blood products may be necessary. Risk of disseminated intravascular coagulation (may be serious). Monitor coagulation parameters, platelet counts, signs/symptoms of bleeding or thrombosis. Permanently discontinue if hypersensitivity reaction is suspected. Hepatic or renal impairment (CrCl <30mL/min). Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for 6 months after the last dose. Pregnancy: risk of fetal B-cell depletion. Nursing mothers: not recommended (during and for 6 months after the last dose).

GAZYVA Classification:

CD20-directed cytolytic monoclonal antibody.

GAZYVA Interactions:

Concomitant live viral vaccines: not recommended during treatment and until B-cell recovery (esp. neonates/infants if exposed to Gazyva in utero). Consider withholding antihypertensives for 12hrs prior to, during, and for 1hr after infusion until BP is stable. Consider withholding drugs that may increase bleeding risk (eg, platelet inhibitors, anticoagulants) esp. during 1st cycle.

Adverse Reactions:

Infusion reactions, neutropenia, fatigue, thrombocytopenia, diarrhea, cough, constipation, pyrexia, upper RTI, arthralgia, sinusitis, asthenia, UTI, headache, insomnia, pneumonia, decreased appetite, alopecia, pruritus.

Generic Drug Availability:

NO

How Supplied:

Single-use vial (40mL)—1