Bendeka injection for chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma

Bendeka is an intravenous chemotherapy medication approved to treat adults with chronic lymphocytic leukemia (CLL) and for patients with indolent B-cell non-Hodgkin lymphoma (NHL) whose disease has progressed during or shortly after treatment with rituximab or a rituximab-containing regimen. It works as an alkylating agent to interfere with the growth of cancer cells.

Bendeka injection is prescribed for:

• Chronic lymphocytic leukemia (CLL): Treatment of adult patients. Efficacy compared to first-line therapies other than chlorambucil has not been established.
• Indolent B-cell non-Hodgkin lymphoma (NHL): Treatment of adult patients with disease progression during or within six months after rituximab or rituximab-containing regimens.

bendamustine hydrochloride

Bendeka contains bendamustine hydrochloride, an alkylating drug that damages the DNA of cancer cells. This damage prevents the cells from dividing and growing, leading to their death. By targeting cancer cells’ DNA, bendamustine helps slow or stop the progression of CLL and certain types of NHL.

Dosage for chronic lymphocytic leukemia (CLL):

• 100 mg/m2 intravenous infusion over 10 minutes on Days 1 and 2 of each 28-day cycle, for up to 6 cycles.
• Delay doses for Grade 4 hematologic toxicity or significant ≥Grade 2 non-hematologic toxicity until recovery to ≤Grade 1 and blood counts improve (ANC ≥ 1 x 109/L, platelets ≥ 75 x 109/L).
• Dose reductions for hematologic toxicity: reduce to 50 mg/m2 or 25 mg/m2 on Days 1 and 2 if ≥Grade 3 toxicity recurs.
• Dose reductions for non-hematologic toxicity: reduce to 50 mg/m2 on Days 1 and 2 for clinically significant ≥Grade 3 toxicity.

Dosage for indolent B-cell non-Hodgkin lymphoma (NHL):

• 120 mg/m2 intravenous infusion over 10 minutes on Days 1 and 2 of each 21-day cycle, for up to 8 cycles.
• Delay doses for Grade 4 hematologic toxicity or significant ≥Grade 2 non-hematologic toxicity until recovery to ≤Grade 1 and blood counts improve (ANC ≥ 1 x 109/L, platelets ≥ 75 x 109/L).
• Dose reductions for hematologic toxicity: reduce to 90 mg/m2 or 60 mg/m2 on Days 1 and 2 if ≥Grade 4 toxicity recurs.
• Dose reductions for non-hematologic toxicity: reduce to 90 mg/m2 or 60 mg/m2 on Days 1 and 2 if ≥Grade 3 toxicity recurs.

Administration and preparation:

• Withdraw required dose from multiple-dose vial (25 mg/mL solution) and dilute into 50 mL of compatible infusion solution (0.9% sodium chloride, 2.5% dextrose/0.45% sodium chloride, or 5% dextrose).
• Infuse intravenously over 10 minutes.
• Prepare admixture as close to administration time as possible.
• Stability of diluted solution varies by diluent and storage condition (e.g., up to 24 hours refrigerated or 6 hours at room temperature for saline or 2.5% dextrose/0.45% saline, shorter at room temperature with 5% dextrose).
• Store unopened vials refrigerated (2°C to 8°C); protect from light.
• Partially used vials are stable for 28 days refrigerated and should be discarded after 6 total dose withdrawals or 28 days.

• Known hypersensitivity to bendamustine, polyethylene glycol 400, propylene glycol, or monothioglycerol.
• History of anaphylactic or anaphylactoid reactions to bendamustine or its components.

Serious warnings and precautions include:

• Myelosuppression: Bendeka causes severe decreases in blood cells. Frequent blood counts are required. Delay or reduce doses if blood counts are too low.
• Infections: Increased susceptibility due to immunosuppression. Monitor for fever and signs of infection. Reactivation of hepatitis B and other infections can occur.
• Progressive multifocal leukoencephalopathy (PML): A rare, often fatal brain infection. Monitor for neurological symptoms, discontinue if suspected.
• Anaphylaxis and infusion reactions: Can cause severe allergic reactions, especially from the second cycle onward. Discontinue for severe reactions. Pre-medication may be used for milder reactions.
• Tumor lysis syndrome: Rapid destruction of tumor cells can cause kidney failure and death. Use preventive measures like hydration and monitor blood chemistries.
• Severe skin reactions: Cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS have been reported. Discontinue if severe skin reactions develop.
• Hepatotoxicity: Monitor liver function tests regularly during treatment.
• Secondary malignancies: Monitor for development of new cancers during and after treatment.
• Extravasation injury: Avoid infiltration at infusion site to prevent severe tissue damage.
• Embryo-fetal toxicity: Bendeka can cause fetal harm. Advise effective contraception during treatment and for specified durations after last dose (6 months for females, 3 months for males).

Common and serious side effects include:

• Severe myelosuppression leading to low blood counts; may cause neutropenic infections including pneumonia, sepsis, and opportunistic infections.
• Infusion-related reactions such as fever, chills, rash, and pruritus; severe anaphylaxis is rare but possible.
• Skin reactions ranging from rash to life-threatening conditions like Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS.
• Liver injury, including fatal cases.
• Infections and infection reactivations (e.g., hepatitis B, cytomegalovirus, tuberculosis, herpes zoster).
• Tumor lysis syndrome with risk of acute kidney injury.

Coadministration with allopurinol may increase the risk of severe skin toxicity. Close monitoring is advised if both drugs are used.

Bendamustine treatment can lead to reactivation of infections; appropriate prophylaxis and monitoring should be considered when used with drugs that affect immune function.

Pregnancy:

Bendeka can cause fetal harm when administered during pregnancy. Animal studies showed adverse developmental effects. Women of reproductive potential should use effective contraception during treatment and for 6 months after the last dose.

Contraception:

Men with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose.

Lactation:

Information on use during breastfeeding is not provided in the supplied label.

Overdose manifestations and management are not detailed in the supplied label information.

Store unopened vials refrigerated between 2°C to 8°C (36°F to 46°F). Protect from light. If refrigerated contents freeze, allow vial to reach room temperature (15°C to 30°C) before use.

After first use, store partially used vial in original carton refrigerated and discard after 28 days.

Prepared admixtures are stable up to 24 hours refrigerated or variable periods at room temperature depending on the diluent used (6 hours for saline or 2.5% dextrose/0.45% saline, 3 hours for 5% dextrose).