General Information

Treanda and Bekinda are rationally designed purine analog and alkylator hybrid. The product damages the DNA in cancer cells, which leads to the normal path of cell death (apoptosis). It also stops cancer cells from dividing to create new cancer cells.

Treanda/Bekinda is specifically indicated for:

• the treatment of chronic lymphocytic leukemia where efficacy relative to first line therapies other than chlorambucil has not been established
• indolent B-cell non-Hodgkin’s lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

Treanda and Bekinda have two main differences:

The first difference is that it takes less time to administer the same dosage of Bendeka compared to Treanda.

• An infusion of Bendeka can be administered over 10 minutes whereas an infusion of Treanda must be administered over 60 minutes.

The second difference is that Bendeka is compatible with polycarbonate or acrylonitrile-butadiene-styrene (ABS)-containing infusion equipment, and Treanda injection is not.

• Treanda Injection cannot be used with closed system transfer devices (CSTDs), adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS) as significant absorption of the active ingredient bendamustine to surfaces containing these ingredients will occur.

Treanda/Bendeka both come as a ready made solution for intravenous administration. Treanda also is available as a powder that requires mixing with sterile water before diluting. 

The recommended initial dose of the drug for the treatment of non-Hodgkin's lymphoma is 120 mg/m2 administered intravenously over 60 minutes on days one and two of a 21-day cycle, up to eight cycles. Treanda administration should be delayed in the event of a Grade 4 hematologic toxicity or clinically significant > Grade 2 non-hematologic toxicity.
Dose modifications for hematologic toxicity: reduce the dose to 90 mg/m2 on days one1 and two of each cycle. If Grade 4 toxicity recurs, reduce the dose to 60 mg/m2 on days one and two of each cycle.
Dose modifications for non-hematologic toxicity: reduce the dose to 90 mg/m2 on days one and two of each cycle. If Grade 3 or greater toxicity recurs, reduce the dose to 60 mg/m2 on days one and two of each cycle.

The recommended initial dose of the drug for the treatment of chronic lymphocytic leukemia is 100 mg/m2 administered intravenously over 30 minutes on days one and two of a 28-day cycle, up to six cycles. Treanda administration should be delayed in the event of Grade 4 hematologic toxicity or clinically significant >Grade 2 non-hematologic toxicity.
Dose modifications for hematologic toxicity: reduce the dose to 50 mg/m2 on days one and two of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m2 on days one and two of each cycle.
Dose modifications for non-hematologic toxicity: reduce the dose to 50 mg/m2 on days one and two of each cycle.

Mechanism of Action

Treanda/Bendeka contains bendamustine hydrochloride, an alkylating drug. Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like benzimidazole ring. Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells. However, the exact mechanism of action of bendamustine remains unknown.

Side Effects

Adverse events associated with the use of Treanda/Bendeka for chronic lymphocytic leukemia may include, but are not limited to, the following:

• Pyrexia
• Nausea
• Vomiting
• Asthenia
• Fatigue
• Malaise
• Weakness
• Dry mouth
• Somnolence
• Cough
• Constipation
• Headache
• Mucosal inflammation
• Stomatitis

Adverse events associated with the use of Treanda/Bendeka for the treatment of non-Hodgkin's lymphoma may include, but are not limited to, the following:

• Nausea
• Fatigue
• Vomiting
• Diarrhea
• Pyrexia
• Ratigue
• Rebrile neutropenia
• Pneumonia
• Hypokalemia
• Dehydration.

Clinical Trial Results

FDA approval for Treanda/Bendeka for the treatment of chronic lymphocytic leukemia was based on the results of an open-label, randomized, controlled multicenter trial in 301 previously-untreated patients with Binet Stage B or C (Rai Stages I - IV) CLL requiring treatment. The subjects received either bendamustine HCL at 100 mg/m2, administered intravenously over a period of 30 minutes on days one and two or chlorambucil at 0.8 mg/kg administered orally on days one and 15 of each 28-day cycle. Efficacy endpoints were objective response rate and progression-free survival. The overall response rate was 59 percent in the bendamustine HCL arm compared to 26 percent in the chlorambucil arm (p).

FDA approval for the treatment of non-Hodgkin's lymphoma was based on the results of a single arm study of 100 subjects with indolent B-cell NHL that had progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. All subjects received bendamustine HCL intravenously at a dose of 120 mg/m2, on days one and two of a 21-day treatment cycle. They were treated for up to eight cycles. Overall response rate was seen in 74 of the subjects (64.3 percent). The median duration of response was 9.2 months.