Ulrich von Grünhagen

PURPOSE: The aim of this multicenter-study was to evaluate the progression-free survival, response rate and toxicity of the combination of bendamustine and rituximab (BR) in patients with mantle cell or low-grade lymphomas in first to third relapse or refractory to previous treatment. PATIENTS AND METHODS: A total of 245 courses (median, four courses per patient) were administered to 63 patients. Bendamustine was given at a dose of 90 mg/m2 as a 30-minute infusion on days 1 and 2, combined with 375 mg/m2 rituximab on day 1, for a maximum of four cycles every 4 weeks. Histologies were 24 follicular, 16 mantle cell, 17 lymphoplasmacytoid, and six marginal zone lymphoma. RESULTS: Fifty-seven of 63 patients responded to BR, corresponding to an overall response rate of 90% (95% CI, 80% to 96%) with a complete remission rate (CR) of 60% (95% CI, 47% to 72%). The median time of progression-free survival was 24 months (range, 5 to 44+ months), and the median duration of overall survival has not yet been reached. In mantle cell lymphomas, BR showed a considerable activity, achieving a response rate of 75% (95% CI, 48% to 93%) with a CR rate of 50%. Myelosuppression was the major toxicity, with 16% grade 3 and 4 leukocytopenia. Thrombocytopenia was rare, with only 3% grade 3 and 4. CONCLUSION: These results demonstrate that the BR combination is a highly active regimen in the treatment of low-grade lymphomas and mantle cell lymphomas.

We report on the response rate and tolerability of Alemtuzumab (Campath-1H) in a series of heavily pretreated patients with B-CLL with a special focus on treatment-related problems. All patients tested positive for CD52 on B-lymphocytes before entering the trial. Thirteen patients with B-chronic lymphocytic leukemia (B-CLL), 1 prolymphocytic leukemia (PLL), 1 mantle cell lymphoma (MCL) and 1 leukemic immunocytoma (IC) transformed into a high-grade NHL were included. Median age was 62 years (range 40-73), and pretreatment consisted of median 3 prior regimens (range 1-11). All patients received 3, 10 and 30 mg of Campath-1H on sequential days, and then were subsequently scheduled for 30 mg 3 times weekly. Nine out of 16 patients responded. One patient attained complete remission (CR), 8 patients achieved partial remission (PR), while 4 patients had stable disease (SD). Three patients had progressive disease (PD). Beginning with initiation of treatment recurrent profound leukopenia became evident in 13 out of 16 patients leading to treatment discontinuation. Severe nonhematological toxicity (WHO grade IV bronchospasm) occurred in the first patient of this series, who initially had no concomitant steroids. Therefore, we developed a steroid co-medication regimen for the first 4 Campath-1H applications with quick tapering thereafter. Following this regimen, no infusion associated side effects WHO grade > II were observed. Infectious complications leading to treatment discontinuation consisted of pulmonary aspergillosis in one and bacterial pneumonia in another case. One patient with refractory B-CLL and Pneumocystis carinii pneumonia plus CMV reactivation died. In summary, Campath-1H appears to be effective against leukemic low-grade B-NHL, also in advanced stage. In our series, application 3 times weekly was not possible due to hematotoxicity. We recommend, therefore, flexible time intervals depending on the leukocyte counts. Whether a cumulative dosage according to 3 x 30 mg Campath-1H for 12 weeks is needed still remains to be clarified.