| Cycle length: 28 days. |
| Drug | Dose and route | Administration | Given on days |
| Rituximab | 375 mg/m2 IV | Dilute in normal saline (NS) or 5% dextrose in water to a final concentration of 1 to 4 mg/mL. Initial infusion: Start at 50 mg/hour; escalate in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour, as tolerated. In the absence of an initial infusion reaction, patients without clinically significant cardiovascular disease may receive subsequent infusions over 90 minutes.* For the 90-minute infusion, administer 20% of the total dose over the first 30 minutes and the remaining 80% over 60 minutes, as tolerated.¶[3] | Day 1 |
| Bendamustine | 90 mg/m2 IVΔ | Dilute◊ in 500 mL NS or 2.5% dextrose/0.45% sodium chloride to a final concentration of 0.2 to 0.6 mg/mL.§ Administer over 60 minutes. | Days 1 and 2 |
| Pretreatment considerations: |
| Emesis risk | - MODERATE.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Premedicate with acetaminophen and diphenhydramine, with or without an H2 receptor blocker, 30 minutes prior to at least the first and second infusions of rituximab.[4] There is no standard premedication for the initial bendamustine dose. Consider premedication with antihistamines, antipyretics, and corticosteroids for patients with a previous grade 1 or 2 infusion reaction to bendamustine.[5-7]
- Refer to UpToDate topics on infusion reactions to therapeutic monoclonal antibodies used for cancer therapy.
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| Vesicant/irritant properties | - Bendamustine is an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation (particularly by avoiding use of closed system transfer devices, adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene [ABS] with Treanda injection solution◊); monitor IV site for redness, swelling, or pain.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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| Infection prophylaxis | - The specific incidence of febrile neutropenia was not reported, however, the incidence of grade 3 or 4 neutropenia was 29 to 49% and the incidence of grade 3 or 4 infection was 7 to 12%.[1,2] Primary prophylaxis with hematopoietic growth factors should be considered on an individual basis. Antiviral prophylaxis and Pneumocystis jirovecii prophylaxis are also individualized.
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
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| Dose adjustment for baseline liver or renal dysfunction | - Treanda should not be used in patients with a creatinine clearance <40 mL/min. Bedenka should not be used in patients with a creatinine clearance <30 mL/min. Bendamustine should be used with caution in patients with mild hepatic and renal impairment. Bendamustine should not be used in patients with moderate to severe (AST or ALT >2.5 times the ULN and total bilirubin >1.5 times the ULN) hepatic impairment.[5-7]
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents; and chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency, conventional cytotoxic agents.
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| Hepatitis screening | - Patients should be screened for hepatitis B and C prior to starting rituximab, and if positive, considered for antiviral prophylaxis.
- Refer to UpToDate topics on hepatitis B virus reactivation associated with immunosuppressive therapy.
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| Monitoring parameters: |
- Obtain CBC with differential weekly (initially).[5-7]
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- Assess electrolytes and liver and renal function prior to each treatment.
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- Carriers of hepatitis B or C virus should be monitored for clinical and laboratory signs of active infection during and following completion of therapy. Rituximab should be discontinued if reactivation occurs.
- Refer to UpToDate topics on hepatitis B virus reactivation associated with immunosuppressive therapy.
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- Monitor IV infusion site for redness, swelling, pain, infection, and necrosis during and after the bendamustine infusion.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Delay treatment if absolute neutrophil count <1000/microL, platelet count <75,000/microL, or if there is an active infection.[4-7] If grade 4 hematologic toxicity occurs, reduce dose to 60 mg/m2 on days 1 and 2 of each cycle.[2,5-7] Further dose reductions or dose re-escalation may be done at the discretion of the physician.
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| Other toxicity | - For grade 3 or greater nonhematologic toxicity, reduce bendamustine dose to 60 mg/m2 on days 1 and 2 of the treatment cycle.[5-7] If toxicity resolves, doses may be cautiously re-escalated on subsequent cycles. Further dose reductions or dose re-escalation may be done at the discretion of the physician.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
