Rituximab In Combination with High-Dose Dexamethasone: An Effective Treatment Option for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4629-4629
Author(s):  
Michael Doubek ◽  
Martin Simkovic ◽  
Anna Panovska ◽  
Monika Hrudkova ◽  
David Belada ◽  
...  
Keyword(s):  
Effective Treatment ◽  
Treatment Option ◽  
Progression Free Survival ◽  
Median Number ◽  
Infectious Complications ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Significant Activity ◽  
Effective Treatment Option ◽  
High Dose Dexamethasone

Abstract Abstract 4629 Background: Patients with refractory CLL have poor outcome despite currently used salvage treatment. Regimens based on high-dose corticosteroids seem to offer a promising treatment option in this scenario. High-dose methylprenisolone combined with rituximab (R-HDMP) demonstrated significant activity in relapsed/refractory CLL but serious infectious complications occurred in a substantial proportion of patients. Pilot data have shown that combination of dexamethasone and rituximab (R-Dex) may provide comparable results with less toxicity. Aims and Methods: We performed a retrospective analysis of the efficacy and safety of R-Dex in patients (pts) with CLL treated at two tertiary centers between April 2006 and February 2010. Patients received two versions of R-Dex regimen: the dose of rituximab was either 500 mg/m2 on day 1, 8, 15, 22 (375 mg/m2 in 1st cycle), repeated every 4 weeks (n=25) or 500 mg/m2 on day 1 (375 mg/m2 in 1st cycle) repeated every 3 weeks (n=16). The dose of dexamethasone was identical in both regimens: 320 mg per cycle (40 mg on day 1–4 and 10–13 or 15–18). Results: R-Dex was administered to 41 patients (19 males) with median age of 68 years (range, 44–81) indicated for treatment according to NCI-WG criteria. Autoimmune hemolytic anemia or thrombocytopenia was the only indication for the treatment in 7 patients. Rai stage III/IV was present in 37/41 pts. IgVH genes were unmutated in 24/29 pts with available results. Cytogenetic aberrations detected by FISH (n=33) revealed del 17p in 7 patients; del 11q in 11 patients; del 13q in 15 patients and trisomy 12 in 5 patients. Median number of previous therapies was 2 (0-8); 29/41 pts were previously treated with fludarabine-based regimens. The effect of R-Dex in evaluable patients without hemolysis (n=32) was: overall response rate (ORR), n= 21 (62%), complete remission (CR), n=6 (18%), partial remission (PR), n=15 (44%), stable disease (SD), n=4 (12%) and progressive disease (PD), n=5 (15%). All patients treated with R-Dex for autoimmune cytopenia achieved complete resolution of hemolysis. Grade III or IV toxicity included infections in 13 patients (32%), steroid diabetes in 6 patients (15%) and rituximab infusion-related side effects in 3 patients (7%). At the time of analysis (February 2010), median progression free survival (PFS) was 9 months; median overall survival has not been reached. There was no difference in ORR, PFS or OS between the two versions of R-Dex regimen. Conclusions: This pilot study shows that R-Dex is a feasible and effective treatment for relapsed/refractory CLL. In particular, R-Dex appears to be highly effective in CLL with autoimmune cytopenias. However, infectious toxicity remains a serious issue. In addition, long-term disease control can be expected in minority of patients only. Interestingly, higher dose of rituximab per cycle did not result in improved efficacy. Supported by research project MZO 00179906 from Ministry of Health, Czech Republic, by research grant MSM 0021620808 and by the Czech Leukemia Study Group for Life. Disclosures: Smolej: Roche: Honoraria; Bayer-Schering: Honoraria; Genzyme: Honoraria.

Rituximab and High-Dose Dexamethasone (R-dex) Is Effective In The Treatment Of Relapsed/Refractory Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4184-4184
Author(s):  
Martin Simkovic ◽  
David Belada ◽  
Monika Motyckova ◽  
Lukas Smolej ◽  
Pavel Zak
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Conflicts Of Interest ◽  
Antimicrobial Prophylaxis ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Published Data ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Tertiary Center

Abstract 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. 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.

MM-003: A phase III, multicenter, randomized, open-label study of pomalidomide (POM) plus low-dose dexamethasone (LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8510-8510 ◽  
Author(s):  
Jesùs F. San-Miguel ◽  
Katja C. Weisel ◽  
Philippe Moreau ◽  
Martha Lacy ◽  
Kevin W. Song ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Median Number ◽  
Phase Iii ◽  
High Dose ◽  
Open Label ◽  
High Dose Dexamethasone ◽  
Intent To Treat

8510 Background: RRMM patients (pts) who have exhausted treatment (Tx) with bortezomib (BORT) and lenalidomide (LEN) or thalidomide have a poor prognosis with short overall survival (OS). HiDEX is a well-established standard Tx in RRMM. POM has demonstrated clinical efficacy in pts refractory to LEN and BORT. MM-003 compared POM + LoDEX vs. HiDEX in RRMM pts who failed LEN and BORT and who progressed on their last Tx. Methods: Pts must have been refractory to last prior Tx (progressive disease [PD] during Tx or within 60 days) and failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Pts were randomized 2:1 to receive 28-day cycles of POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) weekly or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20. Tx continued until PD or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included OS, overall response rate (ORR; ≥ partial response), and safety. Analyses were based on intent to treat. Results: 455 pts were randomized to POM + LoDEX (n = 302) or HiDEX (n = 153). The median number of prior Tx was 5 (range 1-17). 72% were refractory to LEN and BORT. Median follow-up was 4 months. POM + LoDEX significantly extended median PFS (3.6 vs. 1.8 months, HR = 0.45, P < .001) and OS (not reached vs. 7.8 months, HR = 0.53, P < .001) vs. HiDEX. The OS benefit was observed despite 29% of HiDEX pts receiving POM after PD. The trial met the primary endpoint of PFS, crossed the upper boundary for OS superiority, and the Data Monitoring Committee recommended crossover from HiDEX to POM ± DEX. With updated data, the ORR was 21% for POM + LoDEX vs. 3% for HiDEX (P < .001) and 24% vs 3% for pts randomized ≥ 6 months post-enrollment (P < .001). The most frequent grade 3/4 adverse events (AEs) for POM + LoDEX vs. HiDEX were neutropenia (42% vs. 15%), anemia (27% vs. 29%), and infection (24% vs. 23%). Discontinuation due to AEs was infrequent (7% vs. 6%). Updated data will be presented. Conclusions: POM + LoDEX significantly extended PFS and OS vs. HiDEX in pts who failed LEN and BORT. POM + LoDEX should become a standard of care in RRMM pts who have exhausted Tx with LEN and BORT. Clinical trial information: NCT01311687.

ZAP-70 Status Does Not Predict Outcome after Nonmyeloablative Allogeneic Stem-Cell Transplantation (NST) in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) That Fails To Respond to Conventional Chemoimmunotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3028-3028
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Joan Admirand ◽  
Susan O’Brien ◽  
Ming-S. Lee ◽  
...  
Keyword(s):  
Early Time ◽  
Progression Free Survival ◽  
Complete Response ◽  
Allogeneic Transplantation ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Unrelated Donor ◽  
Median Percentage

Abstract Recent studies demonstrated that ZAP-70 is an important prognostic factor in CLL. Patients (pts) who were ZAP-70 positive were reported to have an early time to treatment failure and a shorter survival. We determined the effect of ZAP-70 status on the outcome of NST in pts with advanced relapsed CLL. Between 1999 and 2005, 39 pts were enrolled, ranging in age from 34 to 70 years (median, 57 years). All pts had recurrent advanced CLL and had been previously treated with fludarabine-rituximab-based regimens. Each pt had received 2 to 8 (median, 3) chemotherapy regimens. Thirty-four pts (87%) had active disease at the time of study entry. Using immunohistochemical techniques on marrow biopsy samples, we determined that 25 pts were ZAP-70 positive, 13 were ZAP-70 negative, and 1 was of indeterminate status. All pts received a preparative regimen of fludarabine (30 mg/m2 daily for 3 days), intravenous cyclophosphamide (750 mg/m2 daily for 3 days), and high-dose rituximab, as previously reported. Thirty-five pts underwent allogeneic transplantation from a sibling donor and 4 from a matched unrelated donor. The median number of CD34+ cells infused ranged from 1.96 to 6.6 x 106 /kg (median, 4.7 x 106 /kg). Neutrophil counts recovered to > 0.5 x 109/L at a median of 10 days after NST. Donor cells failed to engraft in 1 patient. The median percentage of donor T cells at day 30 was 68% (range, 0%-100%), and increased to 93% and 100% at days 90 and 180, respectively (P < 0.001). Fourteen pts experienced disease progression after transplantation and required immunomanipulation. The last progressions within the whole group and among those patients who were ZAP-70 positive occurred at 23 and 18 months, respectively after transplantation. By multivariate analysis, chemorefractory disease (P = 0.01) and having mixed T cell chimerism at day 90 (P = 0.02), but not ZAP-70 positivity, were identified as the most significant factors for progression after transplantation. Of the 14 pts who required immunomanipulation after transplantation, 6 experienced a complete response (CR) and 1 had a partial response. Responses occurred after therapy with rituximab and donor lymphocyte infusion (DLI) (median, 1 dose of 1 x 107 CD3+/kg). Overall, of the 38 evaluable patients, 27 (71%) experienced a CR. The incidence of acute grade II-IV GVHD was 45%, whereas the incidence of chronic extensive GVHD, pre- and post-DLI, was 58%. With a median follow-up time of 27 months (range, 4–80 months), the estimated overall survival (OS) and current progression-free survival (CFPS) rates at 4 years was 48% and 44%, respectively. Pts who were ZAP-70 positive had a median follow-up period of 41 months (range, 5–80 months). Their estimated OS and CPFS rates at 4 years were estimated to be 56% and 53%, respectively. These results indicate that NST can overcome the negative prognostic feature of ZAP-70 expression in advanced CLL.

Rituximab for Patients with Chronic Lymphocytic Leukemia: A Systematic Review

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4632-4632
Author(s):  
Kathrin Bauer ◽  
Olaf Weingart ◽  
Ina Monsef ◽  
Skoetz Nicole ◽  
Thomas Elter ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Chronic Lymphocytic Leukemia ◽  
Treatment Option ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Relative Effect ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Effective Treatment Option

Abstract Abstract 4632 Introduction: Chronic lymphocytic leukemia (CLL) accounts for 25% of all leukemias and remains incurable with conventional chemotherapy (CX). Rituximab (R) may be an effective treatment option for CLL patients with the potential to improve overall survival (OS) when given in combination with CX but there is also a risk of more side effects such as infections. This review aims to summarize the evidence for this new treatment option by evaluating the effects on OS, progression-free survival (PFS) and side effects. Methods: MEDLINE and CENTRAL were systematically searched for randomized controlled trials up to April 2010. Trials of patients with CLL comparing CX including R and treatment with CX alone (CX identical in both groups) were included. Clinical trials with previously untreated and pre-treated patients were explored in the main meta-analyses. Trial selection, quality assessment and data extraction were done independently by two review authors. Dichotomous data were analyzed as relative effect measures (i.e. relative risk, RR) with 95% confidence intervals (CI). Time-to-event outcomes were analyzed with hazard ratios (HR) and 95% CI in a random effects model. Results: A total of 992 records were screened. Two eligible trials with 921 untreated (GCLLSG CLL 8 trial (CLL8) and CALGB 9712 trial (CALGB 9712)) and two eligible trials with 604 pre-treated patients (REACH trial (REACH) and NCRI CLL 201 trial) that were fitting the inclusion criteria were identified. The NCLRI CLL 201 trial provided response data only. CALGB 9721 did not report HRs or P-values on OS or PFS and the survival curves for PFS and OS were of low quality, so the provided data were not included in the meta-analysis. Both, CLL8 and REACH examined patients receiving fludarabine (F) and cyclophosphamide (C) with or without R and were meta-analyzed with regard to PFS and OS. PFS (1342 patients) was significantly longer for FCR (HR 0.65, 95% CI [0.48, 0.88]). Analysis of OS (1368 patients) also showed a significantly longer survival for FCR (HR 0.73 (95% CI [0.58, 0.93]). CLL8 provided HRs for the different disease stages and showed significantly improved OS after FCR for Binet B patients only [Binet A: HR 0,19, 95% CI [0.23, 1.613]; Binet B: HR 0.45, 95% CI [0.295, 0.689]; Binet C: HR 1.4, 95% CI [0.843, 2.620]). REACH had not been significant regarding OS (HR 0.83, 95% CI [0.59, 1.17]). With regard to severe hematologic toxicity, meta-analysis of CLL8, REACH and CALGB 9721 showed a significantly higher risk of neutropenia (RR 1.46, CI 95% [1.03, 2.08]) for regimens including R, but there was no statistical difference for thrombocytopenia (RR 1.06, CI 95% [0.60, 1.87]), anemia (RR 0.89 [0.63, 1.26]) or the incidence of severe infections (RR 1.08 CI 95% [0.86, 1.35]). REACH reported a higher rate of secondary malignancies in the FCR-arm (FCR (7%), FC (5%)). Conclusions: This systematic review demonstrates significantly longer OS for CLL patients that received FCR compared to FC (HR 0.65, 95% CI [0.48, 0.88]) and confirms better PFS for patients receiving FCR (HR 0.73 (95% CI [0.58, 0.93]). Adverse events (particularly neutropenia) occurred more often when patients were treated with CX plus R but did not result in an increased infection rate. However, data of CLL8 were only available from the abstract and need to be subsequently confirmed. Disclosures: Hallek: Roche: Consultancy, Honoraria, Research Funding.

Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumours

2019 ◽  
Vol 12 (2) ◽  
pp. 126-134 ◽  
Author(s):  
Shahad Alsadik ◽  
Siraj Yusuf ◽  
Adil AL-Nahhas
Keyword(s):  
Side Effects ◽  
Effective Treatment ◽  
Radionuclide Therapy ◽  
Neuroendocrine Tumours ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Treatment Modalities ◽  
Effective Treatment Option ◽  
Peptide Receptor ◽  
Pancreatic Neuroendocrine Tumours

Background: The incidence of pancreatic Neuroendocrine Tumours (pNETs) has increased considerably in the last few decades. The characteristic features of this tumour and the development of new investigative and therapeutic methods had a great impact on its management. Objective: The aim of this review is to investigate the outcome of Peptide Receptor Radionuclide Therapy (PRRT) in the treatment of pancreatic neuroendocrine tumours. Methods: A comprehensive literature search strategy was used based on two databases (SCOPUS, and PubMed). We considered all studies published in English, evaluating the use of PRRT (177Luteciuim- DOTA-conjugated peptides and 90Yetrium- DOTA- conjugated peptides) in the treatment of pancreatic neuroendocrine tumours as a standalone entity or as a subgroup within the wider category of Gastroenteropancreatic Neuroendocrine Tumours (GEP NETs). Results: PRRT was found to be an effective treatment modality as a monotherapy or in combination with other therapies in the treatment of non-operable and metastatic pNETs where other options are limited. Complete response was reported to be between 2-6% while partial response was achieved in up to 60% of cases. Survival analysis was also impressive. Progression Free Survival (PFS) reached a mean of 34 months and Overall Survival (OS) of 53 months. PRRT also proved to improve patients’ Quality of Life (QoL). Acute and sub-acute side effects like nephrotoxicity and haematotoxicity are usually mild and reversible. Conclusion: PRRT is well tolerated and effective treatment option for non-operable and/or metastatic pNETs. Side effects are usually mild and reversible. Larger randomized controlled trails need to be done to compare PRRT with other treatment modalities and to provide more detailed guidelines regarding patient selections, the choice of PRRT, follow up and response assessment to maximum potential benefit.

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