Ute Kreibich

Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem-cell transplantation or conventional chemotherapy: results of a Phase I clinical trial

Thalidomide is an effective agent for advanced refractory or relapsed multiple myeloma (MM), although dose‐limiting toxicity (DLT) may limit its use. This Phase I study found that a combination of low‐dose thalidomide with bendamustine and prednisolone (BPT) maintained or increased efficacy, whilst avoiding DLT in 28 patients with MM that was refractory or that had relapsed after conventional chemotherapy or high‐dose therapy with stem‐cell support. BPT comprised fixed doses of bendamustine (60 mg/m2) and prednisolone (100 mg), and escalating doses of thalidomide (50, 100, 200 mg). Treatment cycles were repeated every 28 d until the occurrence of maximum response, DLT, or disease progression. Twenty‐four patients responded after at least two cycles (four complete remission, six very good partial remission, 14 partial remission). Median progression‐free and overall survival for all patients was 11 and 19 months respectively. Only mild/moderate non‐haematological side effects were observed and no patient developed dose‐limiting haematotoxicity. Transient grade 3–4 neutropenia was reported in 12 patients, and grade 3–4 thrombocytopenia occurred in two patients. We conclude that BPT therapy was well tolerated in patients with relapsed or refractory MM, with a response rate higher than 80%. The maximum tolerated dose of thalidomide was not reached in this study.

Relapse incidence and leukemia-free survival (LFS) in patients (pts) older than age 60 with AM undergoing stem cell transplantation: A report of the East German Study Group Hematology and Oncology (OSHO).

6523 Background: Complete remission rates similar to those of younger pts are obtained in elderly AML pts (OSHO AML 1997). However, OS and LFS remain dismal because of extremely high relapse rates. In the AML 2004 study, reduced intensity conditioning SCT was introduced to reduce relapse in patients with a compatible related/unrelated donor. In this analysis we compared outcome of patients with a donor to patients without a donor. METHODS Of the 663 pts, 597 were entered into the study specific arm and 66 in the common arm of the German Intergroup Study. Of those 447 and 52 pts were evaluable, respectively. The majority of pts were male (56.9%), the median age 68 years and the median Karnofsky score 80%. Karyotype was normal in 46.9% and unfavorable in 21.2%, while 55.9% had de novo AML. Induction therapy consisted of AraC 100 mg/m2 c. i. over 7 days / Daunorubicin 60 mg/m2 i.v. on days 3 - 5 in the standard arm and of AraC 2g/m2 on days 1, 3, 5 and 7 / mitoxantrone 10 mg/m2 i.v. day 1 - 3 in the study arm. SCT were performed following reduced intensity conditioning. RESULTS CR was observed in 62% of pts after induction in the study arm and in 62% in the standard arm. A total of 76 pts had a stem cell donor and 129 no donor. There was no significant difference between the populations except for median age 68 in the chemotherapy vs. 65 a in the SCT arm (p<0.001). OS at 3 a was 35 ± 6% in the chemotherapy compared to 49 ± 6% in the SCT arm. Accordingly, LFS at 3 a was 27 ± 5% for chemotherapy as compared to 39 ± 7% in the SCT arm (p=0.04) and due to reduced relapse incidence (73±5% vs. 45±7%, respectively; p 0.001). Only SCT and favorable risk cytogenetics were independent factors for increased LFS. Both variables were independent risk factors for lower relapse rate, as was de novo AML. In contrast, high WBC at diagnosis and SCT were significantly associated in a multivariate analysis with increased treatment related mortality. CONCLUSIONS SCT in comparison to chemotherapy is associated with increased LFS and lower relapse independently of cytogenetic risk. The biggest differences in LFS and relapse between SCT and chemotherapy were noted among pts with high risk cytogenetic disease.