Introduction

High-dose methylprednisolone (HDMP) in combination with rituximab is active in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) but serious infections are frequent. Recently published data suggest that high-dose dexamethasone might be equally effective to HDMP despite lower cumulative dose.

Aims

To assess efficacy and safety of high-dose dexamethasone combined with rituximab (R-dex) in relapsed/refractory CLL.

Patients and Methods

A total of 60 pts (pts) with relapsed/refractory CLL treated at a single tertiary center between September 2008 and October 2012 were included in this retrospective analysis. Basic characteristics are summarized in Table 1. The schedule of R-dex consisted of rituximab 500 mg/m2 i.v. day 1 (375 mg/m2 in cycle 1) and dexamethasone 40 mg orally on days 1-4 and 10-13. Treatment was repeated every 3 weeks for a maximum of 8 cycles. All pts received antimicrobial prophylaxis with sulfamethoxazole/trimethoprim and aciclovir.

Table 1

Basic characteristics.

Total number of patients60
Age (median, range) 69 (54-83) 
Males 73% 
Rai stage III/IV 65% 
Bulky lymphadenopathy (≥ 5cm) 58% 
Previous treatment lines (median, range) 2 (1-7) 
Unmutated IgVH 82% 
Del 11q 42% 
Del 17p 19% 
Fludarabine-refractory 50% 
Bulky fludarabine-refractory 33% 
Total number of patients60
Age (median, range) 69 (54-83) 
Males 73% 
Rai stage III/IV 65% 
Bulky lymphadenopathy (≥ 5cm) 58% 
Previous treatment lines (median, range) 2 (1-7) 
Unmutated IgVH 82% 
Del 11q 42% 
Del 17p 19% 
Fludarabine-refractory 50% 
Bulky fludarabine-refractory 33% 
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Results

Median number of administered R-dex cycles was 6 (range, 1-8). The overall response (ORR)/complete remissions (CR) were achieved in 75/3%. At the median follow-up of 9 months, median progression-free survival was 8 months and median overall survival 24 months. Significant predictors of short PFS in univariate analysis were bulky lymphadenopathy (p=0.023) and refractoriness to fludarabine (p=0.02). Interestingly, activity of R-dex in bulky fludarabine-refractory CLL was similar to ofatumumab (ORR 62 %, median PFS, 4 months, median OS, 12 months) (Wierda et al., 2010). R-dex was successfully used as a debulking regimen before allogeneic stem cell transplantation in 8 patients. Serious (CTCAE grade III/IV) infections occurred in 29% of patients; 19% pts developed steroid diabetes requiring temporary short-acting insulin.

Conclusions

Our data show that R-Dex is an active and feasible treatment for patients with relapsed/refractory CLL; however, major infections remain relatively frequent despite combined antimicrobial prophylaxis. In addition, durable responses are infrequent. Therefore, further optimization of this therapeutic approach is warranted. Updated results will be presented.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
chronic lymphocytic leukemia refractory, dexamethasone, rituximab, brachial plexus neuritis, fludarabine, infections, antibiotic prophylaxis, lymphadenopathy, acyclovir, allogeneic stem cell transplant

Author notes

*

Asterisk with author names denotes non-ASH members.

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© 2013 by The American Society of Hematology
2013
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