Five years of experience with rituximab plus high-dose dexamethasone for relapsed/refractory chronic lymphocytic leukemia

Abstract

IntroductionHigh-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 suggested that high-dose dexamethasone might be equally effective as HDMP despite a lower cumulative dose.Material and methodsWe performed retrospective analysis of 60 patients with relapsed/refractory CLL (median age: 66 years; range: 37–86) treated with rituximab plus dexamethasone (R-dex) at a single tertiary center between September 2008 and October 2012. 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 repeated every 3 weeks for a maximum of 8 cycles. Unfavorable prognostic features were frequent (Rai stages III/IV in 67%, unmutated IgVH 82%, del 11q 43%, TP53 mutation/deletion 23%, bulky lymphadenopathy 58% of patients).ResultsOverall response (OR)/complete remission (CR) was achieved in 75/3%. At the median follow-up of 21 months, median progression-free survival (PFS) was 8 months, median time to next treatment 12.9 months and median overall survival 25.5 months. Refractoriness to fludarabine (p = 0.04) and age ≥ 65 years (p = 0.03) were significant predictors of shorter PFS. R-dex was successfully used for debulking before allogenic stem cell transplantation in 7 patients (12%). Serious (CTCAE grade III/IV) infections occurred in 27% of patients; 20% of patients developed steroid diabetes requiring temporary short-acting insulin.ConclusionsOur results show that R-dex is an active and well-tolerated regimen for patients with relapsed/refractory CLL; however, major infections remain frequent despite combined antimicrobial prophylaxis.

Rituximab, Cyclophosphamide and Dexamethasone (RCD) Chemoimmunotherapy for Relapsed Chronic Lymphocytic Leukaemia

“…All considered, the efficacy comparison with other published series is rather difficult; furthermore, whether the addition of cyclophosphamide into the treatment regimen can affect the long‐term outcome for the patients remains controversial. In contrast with previous studies, the presence of del17p deletions and/or TP53 mutations was a significant predictor of shorter progression‐free survival 4,11 …”

“…We previously demonstrated that the combination of rituximab with high doses of dexamethasone (R‐Dex) results in a high response rate in relapsed CLL patients. However, the median progression‐free survival is still relatively poor, that is 7‐8 months 4,5 . The present manuscript describes a retrospective analysis assessing whether the addition of cyclophosphamide into the R‐Dex regimen, with the concurrent reduction of the dexamethasone dose, results in a comparable treatment outcome.…”

Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia

“…Simkovic et al [11] presented retrospective data of Rtx and high-dose dexamethasone combination with an ORR of 75%, median PFS of 8 months, and median OS of 25.5 months. ORR was not dependent on age, but in multivariate analysis, an age of ≥65 years and an absence of therapeutic response (SD/PD) were identified as independent predictors of shorter PFS ( p = 0.002 for both).…”

Review of targeted therapy in chronic lymphocytic leukemia: what a radiologist needs to know about CT interpretation

“…Bulky nodes and confluent adenopathy is commonly seen during relapses or, as noted above, in patients at presentation with 17p or 11q deletion (Fig. 2 ) [ 15 , 16 ]. Rare sites of CLL involvement have been reported, including the central nervous system [ 17 , 18 ].…”