In the 2008, the FDA ( Food and Drug Administration ) has approved Bendamustine hydrochloride ( Treanda ), an intravenously administered alkylating agent, for the treatment of patients with indolent B-cell non-Hodgkin's lymphoma ( NHL ) that progressed during or within 6 months of treatment with Rituximab or a Rituximab-containing regimen.
Bendamustine hydrochloride was evaluated in a single arm trial of 100 patients with indolent B-cell NHL. All patients had disease progression during or within six months of treatment with Rituximab or a Rituximab-containing regimen.
Bendamustine hydrochloride was administered intravenously at a dose of 120 mg/m 2 infused over 60 minutes on days 1 and 2 of a 21-day treatment cycle for up to 8 cycles.
Efficacy was assessed by a blinded independent review committee using the modified International Working Group response criteria for NHL. The efficacy endpoints included overall response rate ( complete responses, complete responses unconfirmed, or partial responses ) and durations of response ( DR ). ORR and median DR were 74% ( 95% CI 64.3, 82.3 ) and 9.2 months ( 95% CI 7.1, 10.8 ), respectively. Complete responses were reported in 13%, complete responses unconfirmed in 4%, and partial responses in 57% of patients treated.
The safety of Bendamustine hydrochloride was evaluated in the above study and an additional study. A total of 176 patients with B-cell NHL who had received prior Rituximab ( 161 patients with indolent lymphoma and 15 with transformed non-Hodgkins lymphoma ) were evaluated for safety.
The most frequently reported non-hematologic adverse reactions reported were nausea ( 75% ), fatigue ( 57% ), vomiting ( 40% ), diarrhea ( 37% ) and pyrexia ( 34% ). The most frequently reported abnormal hematologic laboratory values were lymphopenia ( 99% ), leukopenia ( 94% ), anemia ( 88% ), neutropenia ( 86% ), and thrombocytopenia ( 86% ).
Grade 3 or 4 adverse reactions were reported in 71% of the combined safety population. The most frequently reported non-hematologic Grade 3 or 4 adverse reactions were fatigue ( 11% ), febrile neutropenia ( 6% ), and pneumonia, hypokalemia and dehydration ( each reported in 5% of patients ). The most frequently reported grade 3 or 4 hematologic laboratory abnormalities were lymphocytopenia ( 94% ), neutropenia ( 60% ), leukopenia ( 56% ), thrombocytopenia ( 25% ), and anemia ( 11% ). Three patients died from myelosuppression-related adverse reactions; one each from neutropenic sepsis, diffuse alveolar hemorrhage with grade 3 thrombocytopenia, and pneumonia from a cytomegalovirus infection.
For patients with indolent non-Hodgkins lymphoma, Bendamustine hydrochloride is administered as a 60 minute IV infusion on days 1 and 2 of a 21-day cycle for up to 8 cycles. The recommended dose is 120 mg/m2.
This dose, infusion duration, and cycle length of Bendamustine hydrochloride is different from that approved dosing regimen for the chronic lymphocytic leukemia ( CLL ) indication. For patients with CLL, Bendamustine hydrochloride is administered as a 30 minute IV infusion on days 1 and 2 of a 28-day cycle for up to 6 cycles. The recommended dose for the CLL indication is 100 mg/m2. ( Xagena )
Source: FDA, 2008