4.6 Article

Bortezomib combined with low-dose cytarabine in Intermediate-2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM

Journal

BRITISH JOURNAL OF HAEMATOLOGY
Volume 158, Issue 2, Pages 232-237

Publisher

WILEY-BLACKWELL
DOI: 10.1111/j.1365-2141.2012.09153.x

Keywords

bortezomib; myelodysplastic syndromes; higher-risk MDS; high risk MDS; intermediate-2 risk MDS

Categories

Ask authors/readers for more resources

Marrow cells from patients with higher-risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)-?B activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1.5mg/m2, days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10mg/m2, then 20mg/m2 from days 114), every 28d for four cycles. Median follow-up was 29.7months. Responses were seen in 12 of the 43 patients (28%), including complete response (CR, n=1), marrow-CR (n=3), partial response (PR, n=5) and haematological improvement (HI, n=3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2.5% HI), compared to none in the 12 previously treated patients (P<0.01). Responders had better overall survival (median 18.2 vs. 10 similar to months). One CR and 3 marrow-CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 12 pre-treatment haematotoxicity developed Grade 34 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher-risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available