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Obinutuzumab: Drug information

Obinutuzumab: Drug information
(For additional information see "Obinutuzumab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Hepatitis B virus reactivation:

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients receiving CD20-directed cytolytic antibodies, including obinutuzumab. Screen all patients for HBV infection before treatment initiation. Monitor HBV-positive patients during and after treatment with obinutuzumab. Discontinue obinutuzumab and concomitant medications in the event of HBV reactivation.

Progressive multifocal leukoencephalopathy:

Progressive multifocal leukoencephalopathy (PML), including fatal PML, can occur in patients receiving obinutuzumab.

Brand Names: US
  • Gazyva
Brand Names: Canada
  • Gazyva
Pharmacologic Category
  • Antineoplastic Agent, Anti-CD20;
  • Antineoplastic Agent, Monoclonal Antibody
Dosing: Adult

Note: Consider temporarily withholding antihypertensive therapies for 12 hours prior to, during, and for 1 hour after obinutuzumab administration (due to the risk for hypotension). Consider withholding platelet inhibitors, anticoagulants, or other medications which may increase bleeding risk (especially during the first cycle). Do not administer to patients with an active infection.

Premedication: Premedicate prior to obinutuzumab infusion to prevent infusion reactions (see "Administration"). Administer appropriate tumor lysis syndrome (TLS) prophylaxis with antihyperuricemics and adequate hydration in patients at high risk for TLS prior to initiating obinutuzumab therapy (and prior to subsequent cycles if needed). Antimicrobial prophylaxis is recommended in patients with grade 3 or 4 neutropenia lasting >1 week (continue until neutropenia resolves to ≤ grade 2); consider antiviral and antifungal prophylaxis with severe neutropenia lasting >1 week.

Chronic lymphocytic leukemia, previously untreated

Chronic lymphocytic leukemia, previously untreated:

In combination with chlorambucil (Goede 2014):

Cycle 1: IV: 100 mg on day 1, followed by 900 mg on day 2, followed by 1,000 mg weekly for 2 doses (days 8 and 15); treatment cycle is 28 days.

Cycles 2 through 6: IV: 1,000 mg on day 1 every 28 days for 5 doses.

Off-label dosing/combinations:

Single-agent obinutuzumab (Byrd 2016):

Cycle 1: IV: 100 mg on day 1, followed by 900 mg on day 2, followed by 1,000 mg weekly for 2 doses (days 8 and 15); treatment cycle is 21 days.

Cycles 2 through 8: IV: 1,000 mg on day 1 every 21 days for 7 doses.

In combination with acalabrutinib (Sharman 2020):

Cycle 2: IV: 100 mg on day 1, followed by 900 mg on day 2, followed by 1,000 mg weekly for 2 doses (days 8 and 15); treatment cycle is 28 days (cycle 1 is acalabrutinib only; obinutuzumab begins with cycle 2).

Cycles 3 through 7: IV: 1,000 mg on day 1 every 28 days for 5 doses (continue acalabrutinib until disease progression or unacceptable toxicity).

In combination with ibrutinib (Moreno 2019):

Cycle 1: IV: 100 mg on day 1, followed by 900 mg on day 2, followed by 1,000 mg weekly for 2 doses (days 8 and 15); treatment cycle is 28 days.

Cycles 2 through 6: IV: 1,000 mg on day 1 every 28 days for 5 doses (continue ibrutinib until disease progression or unacceptable toxicity).

In combination with venetoclax (in patients with coexisting conditions) (Fischer 2019):

Cycle 1: IV: 100 mg on day 1, followed by 900 mg on day 2 (or 1,000 mg on day 1), followed by 1,000 mg weekly for 2 doses (days 8 and 15); treatment cycle is 28 days (venetoclax is initiated on day 22 of cycle 1).

Cycles 2 through 6: IV: 1,000 mg on day 1 every 28 days for 5 doses (continue venetoclax until the end of cycle 12).

Follicular lymphoma, previously untreated

Follicular lymphoma, previously untreated (Marcus 2017):

Note: Patients with complete response or partial response to the initial 6 or 8 cycles of combination therapy (with either bendamustine or cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] or cyclophosphamide, vincristine, and prednisone [CVP]) should continue on obinutuzumab as monotherapy for up to 2 years.

In combination with bendamustine (induction):

Cycle 1: IV: 1,000 mg weekly for 3 doses on day 1, day 8, and day 15; treatment cycle is 28 days.

Cycles 2 through 6: IV: 1,000 mg on day 1 every 28 days for 5 doses.

In combination with CHOP (induction):

Cycle 1: IV: 1,000 mg weekly for 3 doses on day 1, day 8, and day 15; treatment cycle is 21 days.

Cycles 2 through 8: IV: 1,000 mg on day 1 every 21 days for 5 combination therapy doses (in combination with CHOP in cycles 2 through 6), followed by 1,000 mg on day 1 every 21 days for 2 doses (as monotherapy) in cycles 7 and 8.

In combination with CVP (induction):

Cycle 1: IV: 1,000 mg weekly for 3 doses on day 1, day 8, and day 15; treatment cycle is 21 days.

Cycles 2 through 8: IV: 1,000 mg on day 1 every 21 days for 7 doses.

Obinutuzumab monotherapy continuation: 1,000 mg once every 2 months for up to 2 years beginning ~2 months after the last induction phase obinutuzumab dose.

Follicular lymphoma, relapsed/refractory

Follicular lymphoma, relapsed/refractory (Cheson 2018; Sehn 2016):

Note: Patients with stable disease, complete response, or partial response after 6 cycles of combination therapy (with bendamustine) should continue on obinutuzumab as monotherapy for up to 2 years.

Cycle 1: IV: 1,000 mg weekly for 3 doses on day 1, day 8, and day 15 (in combination with bendamustine); treatment cycle is 28 days.

Cycles 2 through 6: IV: 1,000 mg on day 1 every 28 days for 5 doses (in combination with bendamustine).

Obinutuzumab monotherapy: IV: 1,000 mg once every 2 months for up to 2 years beginning ~2 months after the last induction phase obinutuzumab dose.

Missed doses:

Chronic lymphocytic leukemia: Administer the missed dose as soon as possible; adjust dosing schedule to maintain the time interval between doses. In some cases, patients who do not complete the day 1 cycle 1 dose may proceed to the day 2 cycle 1 treatment (if appropriate).

Follicular lymphoma: Administer the missed dose as soon as possible; adjust dosing schedule accordingly to maintain the time interval between chemotherapy cycles. During obinutuzumab monotherapy, maintain the original dosing schedule for subsequent doses.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment is not necessary in patients with renal impairment and no need for dosage adjustment is expected in patients on hemodialysis (Krens 2019).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). However, no need for dosage adjustment is expected (Krens 2019).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult
Obinutuzumab Dosage Modification for Adverse Reactions

Adverse reaction

Severity

Dosage modification

a Appropriate symptom management may also include glucocorticoids, epinephrine, bronchodilators, and/or oxygen.

Hematologic toxicity (concomitant chemotherapy may also require dose reduction or delay)

Neutropenia

Grade 3 or 4

Consider treatment interruption and use of granulocyte colony-stimulating factors. In patients with severe and long-lasting (>1 week) neutropenia, antimicrobial prophylaxis is recommended until neutropenia improves to grade 1 or 2. Consider antiviral and antifungal prophylaxis in patients with severe and long-lasting (>1 week) neutropenia.

Thrombocytopenia

Grade 3 or 4

Consider treatment interruption. Platelet transfusions may be necessary.

Other cytopenia

Grade 3 or 4

Consider treatment interruption.

Nonhematologic toxicity

Hypersensitivity

Any

If a hypersensitivity reaction is suspected during or after an infusion, stop the infusion and permanently discontinue treatment.

Infusion reaction

Mild or moderate (grade 1 and 2)

Reduce infusion rate or interrupt infusion and manage symptoms as appropriatea. Upon symptom resolution, continue or resume infusion. If no further infusion reaction symptoms occur, may resume infusion rate escalation as appropriate for the treatment cycle dose. For chronic lymphocytic leukemia (CLL) only, day 1 (cycle 1) infusion rate may be increased back up to a maximum of 25 mg/hour after 1 hour (but not increased further).

Severe (grade 3)

Interrupt infusion; manage symptoms as appropriatea.

Standard infusion rate: Upon symptom resolution, may reinitiate infusion at no more than 50% of the rate at which the reaction occurred. If no further infusion reaction symptoms occur, may resume infusion rate escalation as appropriate for the treatment cycle dose. For CLL only, day 1 (cycle 1) infusion rate may be increased back up to a maximum of 25 mg/hour after 1 hour. Permanently discontinue if ≥ grade 3 infusion-related symptoms occur upon rechallenge.

90-minute infusion rate (in follicular lymphoma): Upon symptom resolution, may reinitiate infusion at no more than 50% of the rate at which the reaction occurred and not greater than 400 mg/hour. Administer subsequent infusions at the standard infusion rate. Permanently discontinue if ≥ grade 3 infusion-related symptoms occur upon rechallenge.

Life-threatening (grade 4)

Discontinue infusion immediately and manage symptoms as appropriatea; permanently discontinue therapy.

Infection

Any

Consider treatment interruption (do not administer to patients with active infection).

Progressive multifocal leukoencephalopathy

Suspected

Discontinue obinutuzumab and consider discontinuation or dose reduction of any concomitant chemotherapy or immunosuppressive therapy.

Tumor lysis syndrome

Any

Correct electrolyte abnormalities; administer supportive care, including dialysis as indicated.

Viral hepatitis

Any

Discontinue obinutuzumab (and concomitant medications) and initiate appropriate antiviral therapy if viral hepatitis develops.

Other toxicity

≥ grade 2

Consider treatment interruption.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Gazyva: 1000 mg/40 mL (40 mL)

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Gazyva: 1000 mg/40 mL (40 mL)

Administration: Adult

IV: For IV infusion only. Do not administer IV push or as a bolus. Administer through a dedicated IV line; do not mix with or infuse with other medications. May use PVC or non-PVC administration sets. Premedication with acetaminophen, an antihistamine, and a glucocorticoid (dexamethasone or methylprednisolone) may be required to prevent infusion reactions (see below). In patients with severe (grade 3 or 4) neutropenia lasting more than 1 week, antimicrobial prophylaxis is strongly recommended (continue until neutropenia resolves to grade 1 or 2); antiviral and antifungal prophylaxis should be considered.

Premedication to prevent infusion reactions:

Chronic lymphocytic leukemia (CLL) (cycle 1 [days 1 and 2]) and follicular lymphoma (FL) (day 1): All patients should receive acetaminophen (650 to 1,000 mg) and an antihistamine (eg, diphenhydramine 50 mg) at least 30 minutes prior to obinutuzumab infusion. In addition, an IV glucocorticoid (dexamethasone 20 mg or methylprednisolone 80 mg [hydrocortisone has not been effective in reducing the rate of infusion reactions and is not recommended]) should be administered at least 1 hour prior to obinutuzumab infusion. If a glucocorticoid-containing chemotherapy regimen is administered on the same day as obinutuzumab, the glucocorticoid may be administered as an oral medication if administered at least 1 hour prior to obinutuzumab (an IV glucocorticoid is therefore not required).

All subsequent infusions: All patients should receive acetaminophen 650 to 1,000 mg at least 30 minutes prior to obinutuzumab infusion.

If patients experienced grade 1 or 2 infusion-related reaction with previous infusion: Administer an antihistamine (eg, diphenhydramine 50 mg) in addition to acetaminophen at least 30 minutes prior to obinutuzumab infusion.

If patients experienced a grade 3 infusion-related reaction with previous infusion or have a lymphocyte count >25,000 cells/mm3 prior to next treatment: Administer an IV glucocorticoid (dexamethasone 20 mg or methylprednisolone 80 mg [hydrocortisone has not been effective in reducing the rate of infusion reactions and is not recommended]) at least 1 hour prior to obinutuzumab infusion, in addition to acetaminophen and an antihistamine at least 30 minutes prior to obinutuzumab infusion.

Infusion rate:

CLL:

Cycle 1 (day 1): Infuse at 25 mg/hour over 4 hours; do not increase the infusion rate.

Cycle 1 (day 2): If no reaction to previous infusion, initiate infusion at 50 mg/hour for 30 minutes; if tolerated, may escalate rate in increments of 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour. If an infusion reaction occurred during the previous infusion, initiate infusion at 25 mg/hour for 30 minutes; if tolerated, may escalate rate in increments of up to 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

Cycle 1 (days 8 and 15), and cycles 2 through 6 (day 1): If no reaction to previous infusion and the final infusion rate was 100 mg/hour or faster, initiate infusion at 100 mg/hour for 30 minutes; if tolerated, may escalate infusion rate in increments of 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour. If an infusion reaction occurred during the previous infusion, initiate infusion at 50 mg/hour for 30 minutes; if tolerated, may escalate rate in increments of 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

FL (previously untreated or relapsed/refractory): Standard infusion rate:

Cycle 1 (day 1): Initiate infusion at 50 mg/hour for 30 minutes; if tolerated, may escalate rate in increments of 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

All subsequent infusions: If no reaction or grade 1 reaction to previous infusion and the final infusion rate was 100 mg/hour or faster, initiate infusion at 100 mg/hour for 30 minutes; if tolerated, may escalate rate in increments of 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour. If a grade 2 or higher infusion reaction occurred during the previous infusion, initiate infusion at 50 mg/hour for 30 minutes; if tolerated, may escalate rate in increments of 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

FL (previously untreated or relapsed/refractory) : 90-minute infusion rate:

Note: Consider a 90-minute infusion rate for patients with FL who do NOT experience a ≥ grade 3 infusion reaction to obinutuzumab in cycle 1 and subsequent cycles.

Cycle 1 (day 1): Initiate infusion at 50 mg/hour for 30 minutes; if tolerated, may escalate rate in increments of 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

Cycle 1 (days 8 and 15): If no reaction or grade 1 reaction to previous infusion and the final infusion rate was 100 mg/hour or faster, initiate infusion at 100 mg/hour for 30 minutes; if tolerated, may escalate rate in increments of 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour. If a grade 2 or higher infusion reaction occurred during the previous infusion, initiate infusion at 50 mg/hour for 30 minutes; if tolerated, may escalate rate in increments of 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

All subsequent cycles/infusions (including monotherapy): If no ≥ grade 3 infusion reaction occurred during cycle 1, infuse at 100 mg/hour for 30 minutes, then infuse at 900 mg/hour for ~60 minutes. If a grade 1 or 2 infusion reaction with ongoing symptoms, or a ≥ grade 3 infusion reaction occurred during the previous ~90-minute infusion, administer all subsequent obinutuzumab infusions at the standard infusion rate.

Use: Labeled Indications

Chronic lymphocytic leukemia: Treatment of previously untreated chronic lymphocytic leukemia (in combination with chlorambucil).

Follicular lymphoma:

Previously untreated: Treatment of previously untreated stage II bulky, stage III, or stage IV follicular lymphoma in combination with chemotherapy, followed by obinutuzumab monotherapy in patients achieving at least a partial remission.

Relapsed/refractory: Treatment of follicular lymphoma (in combination with bendamustine followed by obinutuzumab monotherapy) in patients who relapsed after, or are refractory to, a rituximab-containing regimen.

Medication Safety Issues
Sound-alike/look-alike issues:

Obinutuzumab may be confused with blinatumomab, dinutuximab, obiltoxaximab, ocrelizumab, ofatumumab, olaratumab, omalizumab, rituximab

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults with the standard infusion rate in combination with chlorambucil or bendamustine unless incidence is identified as having occurred during the monotherapy phase.

>10%:

Dermatologic: Pruritus (11%), skin rash (monotherapy: ≥10%; combination therapy: 17%)

Endocrine & metabolic: Hyperkalemia (20% to 33%), hypernatremia (16%), hyperuricemia (28%), hypoalbuminemia (23% to 33%), hypocalcemia (32% to 39%), hypokalemia (14%), hyponatremia (26%), hypophosphatemia (36% to 41%)

Gastrointestinal: Constipation (8% to 32%) decreased appetite (14%), diarrhea (monotherapy: ≥10%; combination therapy: 10% to 30%; grades 3/4: 2% to 3%)

Genitourinary: Urinary tract infection (monotherapy: ≥10%; combination therapy: 5% to 13%)

Hematologic & oncologic: Anemia (12% to 39%; grades 3/4: 5% to 10%), hemorrhage (12%; grades 3/4: 4%), hypoproteinemia (32%), leukopenia (84% to 92%; grades 3/4: 17% to 49%), lymphocytopenia (monotherapy: grades 3/4: 5% to 23%; combination therapy: 80% to 97%; grades 3/4: 33% to 92%), neutropenia (monotherapy: 13% to 20%; grades 3/4: 10% to 25%; combination therapy: 37% to 84%; grades 3/4: 33% to 59%; onset ≥28 days after completion of treatment: 4% to 16%; lasting ≥28 days: 1% to 3%), thrombocytopenia (14% to 68%; grades 3/4: 7% to 13%; onset within 24 hours of infusion: 4%)

Hepatic: Hyperbilirubinemia (21%), increased serum alanine aminotransferase (28% to 50%), increased serum alkaline phosphatase (18% to 27%), increased serum aspartate aminotransferase (27% to 44%)

Hypersensitivity: Infusion-related reaction (monotherapy: 8% to 9%; combination therapy: 66% to 72%, cycle 1: 37% to 65%, subsequent cycles: ≤23% [dependent on dose, cycle, and use of premedications]; can be severe infusion-related reaction)

Infection: Herpes virus infection (monotherapy: 13%; combination therapy: 18%), infection (38% to 82%)

Nervous system: Fatigue (monotherapy: ≥10%; combination therapy: 40%), headache (18%), insomnia (15%)

Neuromuscular & skeletal: Arthralgia (12% to 16%), musculoskeletal signs and symptoms (including musculoskeletal pain: monotherapy: 20%; combination therapy: 18% to 54%)

Renal: Increased serum creatinine (30%)

Respiratory: Cough (monotherapy: 23%; combination therapy: 10% to 35%), pneumonia (14%), respiratory tract infection (monotherapy: ≥10%; combination therapy: 14%), upper respiratory tract infection (monotherapy: 40%; combination therapy: 36% to 50%)

Miscellaneous: Fever (9% to 19%)

1% to 10%:

Hematologic & oncologic: Febrile neutropenia (6%), tumor lysis syndrome (grades 3/4: ≤2%)

Immunologic: Antibody development (≤7%)

Infection: Sepsis (7%)

Neuromuscular & skeletal: Back pain (5%)

Respiratory: Nasopharyngitis (6%)

<1%: Hematologic & oncologic: Disseminated intravascular coagulation

Frequency not defined:

Cardiovascular: Exacerbation of heart disease

Hepatic: Fulminant hepatitis, hepatic failure

Infection: JC virus infection, reactivation of HBV

Nervous system: Progressive multifocal leukoencephalopathy

Postmarketing:

Gastrointestinal: Gastrointestinal perforation

Hypersensitivity: Hypersensitivity reactions, serum sickness

Contraindications

Known hypersensitivity reactions (eg, anaphylaxis) to obinutuzumab or any component of the formulation; serum sickness with prior obinutuzumab use.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Severe and life-threatening (grade 3 and 4) neutropenia (including neutropenic fever) has been observed in clinical trials. Neutropenia may have a late onset (>28 days after therapy completion) and/or be prolonged (duration >28 days). Consider administration of granulocyte colony-stimulating factors in patients who develop grade 3 or 4 neutropenia. Severe and life-threatening thrombocytopenia has also been reported when used in combination with chemotherapy. In a small percentage of patients, thrombocytopenia occurred acutely (within 24 hours) after obinutuzumab administration. Fatal hemorrhagic events have been reported. Consider withholding platelet inhibitors, anticoagulants, or other medications which may increase bleeding risk (especially during the first cycle).

• Disseminated intravascular coagulation: Disseminated intravascular coagulation (DIC), which may be severe or fatal, has occurred. Most cases involved platelet and laboratory coagulation parameter changes following the first infusion and resolved by day 8; DIC was associated with infusion-related reactions and/or tumor lysis syndrome in some cases. If DIC occurs, institute supportive care.

• Hepatitis B virus reactivation: Hepatitis B virus (HBV) reactivation may occur with use of CD20-directed cytolytic antibodies (including obinutuzumab) and may result in fulminant hepatitis, hepatic failure, and death. Reactivation has occurred in patients who are hepatitis B surface antigen (HBsAg) positive as well as in those who are HBsAg negative but are anti-HBc positive; HBV reactivation has also been observed in patients who had previously resolved HBV infection. HBV reactivation has been reported for other CD20-directed antibodies after therapy discontinuation. Reactivation of HBV replication is often followed by hepatitis. Use cautiously in patients who show evidence of prior HBV infection (eg, HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive); consult with appropriate clinicians regarding monitoring and consideration of antiviral therapy before and/or during obinutuzumab treatment. The safety of resuming obinutuzumab treatment following HBV reactivation is not known; discuss reinitiation of therapy in patients with resolved HBV reactivation with health care providers experienced in HBV management.

• Hypersensitivity/serum sickness: Hypersensitivity reactions have been reported with obinutuzumab. Signs of immediate-onset hypersensitivity included dyspnea, bronchospasm, hypotension, urticaria, and tachycardia. Late-onset hypersensitivity (diagnosed as serum sickness) has also been reported with obinutuzumab; symptoms included chest pain, diffuse arthralgia, and fever. Hypersensitivity reactions may be difficult to clinically differentiate from infusion-related reactions. However, hypersensitivity very rarely occurs with the initial infusion and generally occurs after a prior exposure.

• Infection: Bacterial, fungal, and new or reactivated viral infections may occur during and/or following obinutuzumab therapy; serious and/or fatal infections have been reported. Grade 3 and higher infections have been observed (during and after treatment) when obinutuzumab was administered in combination with chemotherapy followed by obinutuzumab monotherapy. A higher incidence of grade 3 to 5 infections (including during monotherapy and after treatment) have been observed when obinutuzumab was administered in combination with bendamustine (compared to cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] or cyclophosphamide, vincristine, and prednisone [CVP]). Patients with a history of recurrent or chronic infections may be at increased risk.

• Infusion reaction: May cause severe and life-threatening infusion reactions; reactions may include bronchospasm, dyspnea, chest discomfort, tachycardia, larynx and throat irritation, wheezing, laryngeal edema, flushing, rash, hypertension, hypotension, fever, dizziness, nausea, vomiting, diarrhea, headache, fatigue, and/or chills. Infusion reactions occur more frequently with the first 1,000 mg infused or on day 1 of the infusion. Infusion reactions have occurred within 24 hours of receiving obinutuzumab; reactions with subsequent infusions have also occurred. Premedicate prior to infusion. Patients with preexisting cardiac or pulmonary conditions may be at higher risk for infusion reactions. Because infusion reaction may include hypotension, consider temporarily withholding antihypertensive therapies for 12 hours prior to, during, and for 1 hour after administration (consider risks/benefits of withholding antihypertensive therapy in patients at risk for hypertensive crisis).

• Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy (PML) resulting in death may occur with obinutuzumab. PML is due to John Cunningham virus infection. Consider PML in any patient with new onset or worsening neurological symptoms and evaluate promptly if PML is suspected.

• Tumor lysis syndrome: Tumor lysis syndrome (TLS) has been reported with obinutuzumab (some cases fatal). Patients with high tumor burden, high circulating lymphocyte counts (>25,000/mm3), or renal impairment are at higher risk for TLS. Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, and/or hyperphosphatemia may occur.

Concurrent drug therapy issues:

• Immunizations: Administration of live virus vaccines during treatment (and until B-cell recovery) is not recommended; the safety and efficacy of immunization with live or attenuated viral vaccines during or after obinutuzumab therapy has not been determined. If obinutuzumab exposure occurs during pregnancy, the safety and timing of live virus vaccinations for the infant should be evaluated.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Anticoagulants: May enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blood Pressure Lowering Agents: Obinutuzumab may enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccines: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of COVID-19 Vaccines. Management: Administer COVID-19 vaccine 2 to 4 weeks prior to the next scheduled dose of anti-CD20 therapy, if used chronically for the treatment of autoimmune disease. Revaccinate 6 months after completion of anti-CD20 therapy if used over a limited period. Risk D: Consider therapy modification

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Patients who could become pregnant should use effective contraception during therapy and for 6 months after the last obinutuzumab dose.

Pregnancy Considerations

Obinutuzumab is a humanized monoclonal antibody (IgG1). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Based on the mechanism of action and on animal data, if exposure occurs during pregnancy, B-cell counts may be depleted and immunologic function may be affected in the neonate after birth. Administration of live vaccines to neonates and infants exposed in utero should be avoided until after B-cell recovery.

Breastfeeding Considerations

It is not known if obinutuzumab is present in breast milk.

However, endogenous human immunoglobulin can be detected in milk. Although antibodies in breast milk may not enter the breastfed infant's circulations in substantial amounts, the manufacturer recommends discontinuing breastfeeding during therapy and for 6 months after the last obinutuzumab dose.

Monitoring Parameters

CBC with differential (at regular intervals), renal function, electrolytes, uric acid (during initial treatment days if at risk for tumor lysis syndrome); hepatitis B screening in all patients (HBsAg and anti-HBc measurements) prior to therapy initiation.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Monitor for clinical and laboratory signs of hepatitis or active hepatitis B infection (during and for up to 12 months after therapy completion). Monitor for signs or symptoms of infusion reaction (eg, bronchospasm, dyspnea, chest discomfort, tachycardia, larynx and throat irritation, wheezing, laryngeal edema, flushing, rash, hypertension, hypotension, fever, dizziness, nausea, vomiting, diarrhea, headache, fatigue, and/or chills) during the entire infusion; monitor patients with preexisting cardiac or pulmonary conditions more frequently during infusion and in the postinfusion period. Monitor fluid status. Monitor for signs/symptoms of bleeding episodes due to thrombocytopenia (particularly during cycle 1), hypersensitivity, infection, and tumor lysis syndrome (assess fluid balance). Monitor for signs/symptoms of progressive multifocal leukoencephalopathy (PML; focal neurologic deficits, which may present as hemiparesis, visual field deficits, cognitive impairment, aphasia, ataxia, and/or cranial nerve deficits); evaluate for PML with brain MRI, lumbar puncture, and neurologist consultation. Monitor coagulation parameters, platelet counts, and for signs and symptoms of bleeding and thrombosis in patients suspected of having disseminated intravascular coagulation.

Mechanism of Action

Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody. The CD20 antigen is expressed on the surface of pre B- and mature B-lymphocytes; upon binding to CD20, obinutuzumab activates complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis, resulting in cell death (Sehn 2012).

Pharmacokinetics

Distribution: Vd: ~4.1 to 4.3 L.

Half-life elimination: 25.5 to 35.3 days.

Excretion: Clearance: 0.08 to 0.11 L/day.

Pricing: US

Solution (Gazyva Intravenous)

1000 mg/40 mL (per mL): $219.02

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Gavyza (RO);
  • Gazyva (AT, AU, BR, CL, CR, CU, DO, GR, GT, HK, HN, IL, JP, KR, LB, MY, NI, NL, NZ, PA, PH, SG, SV, TH, TW, UA);
  • Gazyvaro (AT, BE, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, HR, HU, IE, IS, LT, LV, MT, NO, PL, PT, RO, RU, SE, SI, SK)


For country abbreviations used in Lexicomp (show table)
  1. Byrd JC, Flynn JM, Kipps TJ, et al. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia. Blood. 2016;127(1):79-86. doi: 10.1182/blood-2015-03-634394. [PubMed 26472752]
  2. Cheson BD, Chua N, Mayer J, et al. Overall survival benefit in patients with rituximab-refractory indolent non-hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018;36(22):2259-2266. doi:10.1200/JCO.2017.76.3656 [PubMed 29584548]
  3. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236. doi: 10.1056/NEJMoa1815281. [PubMed 31166681]
  4. Gazyva (obinutuzumab) [prescribing information]. South San Francisco, CA: Genentech Inc; July 2022.
  5. Gazyva (obinutuzumab). Mississauga, Ontario, Canada: Hoffmann-La Roche Ltd; July 2018.
  6. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-1110. doi: 10.1056/NEJMoa1313984. [PubMed 24401022]
  7. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  8. Krens SD, Lassche G, Jansman FGA, et al. Dose recommendations for anticancer drugs in patients with renal or hepatic impairment. Lancet Oncol. 2019;20(4):e200-e207. doi:10.1016/S1470-2045(19)30145-7 [PubMed 30942181]
  9. Marcus R, Davies A, Ando K, et al. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017;377(14):1331-1344. doi: 10.1056/NEJMoa1614598. [PubMed 28976863]
  10. Moreno C, Greil R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43-56. doi: 10.1016/S1470-2045(18)30788-5. [PubMed 30522969]
  11. Morschhauser FA, Cartron G, Thieblemont C, et al. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013;31(23):2912-2919. [PubMed 23835718]
  12. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. [PubMed 22235228]
  13. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. [PubMed 19626656]
  14. Radford J, Davies A, Cartron G, et al. Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (B021000). Blood. 2013;122(7):1137-1143. [PubMed 23843495]
  15. Sehn LH, Assouline SE, Stewart DA, et al. A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies. Blood. 2012;119(22):5118-5125. [PubMed 22438256]
  16. Sehn LH, Chua N, Mayer J, et al. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016;17(8):1081-1093. [PubMed 27345636]
  17. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278-1291. doi:10.1016/S0140-6736(20)30262-2 [PubMed 32305093]
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