Single-agent purine analogues for the treatment of chronic lymphocytic leukaemia: A systematic review and meta-analysis

2006 ◽  
Vol 32 (5) ◽  
pp. 377-389 ◽  
Author(s):  
Michael Steurer ◽  
Georg Pall ◽  
Sue Richards ◽  
Guido Schwarzer ◽  
Julia Bohlius ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Meta Analysis ◽  
Single Agent ◽  
Purine Analogues

scholarly journals Use of anticoagulants and antiplatelet in patients with chronic lymphocytic leukaemia treated with single-agent ibrutinib

2017 ◽  
Vol 178 (2) ◽  
pp. 286-291 ◽  
Author(s):  
Jeffrey A. Jones ◽  
Peter Hillmen ◽  
Steven Coutre ◽  
Constantine Tam ◽  
Richard R. Furman ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Single Agent

scholarly journals Systematic review and meta-analysis of gemcitabine-based chemotherapy after FOLFIRINOX in advanced pancreatic cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592090540 ◽  
Author(s):  
Victor H. F. de Jesus ◽  
Marcos P. G. Camandaroba ◽  
Vinicius F. Calsavara ◽  
Rachel P. Riechelmann
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Eligibility Criteria ◽  
Grade 3 ◽  
Advanced Pancreatic Adenocarcinoma

Background: There are no randomized data to guide treatment decisions for patients with advanced pancreatic adenocarcinoma following first-line FOLFIRINOX. We performed a systematic review and meta-analysis of studies using gemcitabine-based chemotherapy after FOLFIRINOX to assess treatment efficacy and toxicity. Methods: We included studies published between 2011 and 2018 that evaluated the efficacy and toxicity of gemcitabine-based chemotherapy after FOLFIRINOX in patients with advanced pancreatic adenocarcinoma. We searched PubMed, Embase, Scopus, and Web of Science. Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate, and progression-free survival (PFS). We used the random-effects model to generate pooled estimates for proportions. Results: Sixteen studies met the eligibility criteria. Overall, ORR was 10.8%, DCR was 41.1%, and any grade 3/4 toxicity rate was 28.6%. In subgroup analyses, gemcitabine plus nab-paclitaxel was associated with superior ORR (14.4 versus 8.4%; p = 0.038) and DCR (53.5 versus 30.5%; p < 0.001) compared with single-agent gemcitabine. Median PFS ranged from 1.9 to 6.4 months and numerically favored gemcitabine plus nab-paclitaxel. Conclusions: Our study suggests gemcitabine-based chemotherapy likely outperforms best supportive care after FOLFIRINOX in advanced pancreatic cancer. Also, gemcitabine plus nab-paclitaxel seems to be more active than single-agent gemcitabine (CRD42018100421).

Single-agent Smac-mimetic compounds induce apoptosis in B chronic lymphocytic leukaemia (B-CLL)

2013 ◽  
Vol 37 (7) ◽  
pp. 809-815 ◽  
Author(s):  
Cinzia Scavullo ◽  
Federica Servida ◽  
Daniele Lecis ◽  
Francesco Onida ◽  
Carmelo Drago ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Single Agent ◽  
Smac Mimetic

Correlation between TP53 Deletion and Protein Overexpression in Chronic Lymphocytic Leukaemia and Its Impact on Prognostic.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2076-2076
Author(s):  
Paloma Martin ◽  
Toon Min ◽  
Alison Morilla ◽  
Sarah Hockley ◽  
Ayoma D. Attygale ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
P53 Protein ◽  
Clinical Stage ◽  
Fish Analysis ◽  
Protein Overexpression ◽  
Purine Analogues ◽  
P53 Overexpression ◽  
Bone Marrow Biopsies ◽  
Female Ratio

Abstract B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by a highly variable clinical course. TP53 abnormalities in B-CLL are strongly associated with resistance to purine analogues, short survival and large-cell transformation. Several methods can be used to investigate TP53 inactivation: FISH (gene deletion), immunohistochemistry -IHC- (protein overexpression), and DNA sequencing (mutations). The relationship between TP53 deletion and p53 protein overexpression is unclear, and it is uncertain which method is the best to assess TP53 dysfunction and which provides the most useful clinical information. In 92 CLL patients we have correlated the frequency of p53 protein overexpression by IHC, with TP53 deletion status by FISH and subsequently we have examined the response to Fludarabine in these patients. The male/female ratio was 1.35 (52M/40F), with a median age at diagnosis of 54 years (range 25–78 years). The distribution of clinical stage at diagnosis was as follows: 47% (43 cases) stage A, 16% (15 cases) stage A progressive, 14% (13 cases) stage B, 11% (10 cases) stage C, and unknown in 12% (11 cases). Fourteen cases (15%) were untreated and seventy-eight cases (85%) were previously treated. Among the latter, 66 (84%) received Fludarabine, and 9 (11%) received Campath-1H (as a first line of treatment in 5 patients). In all cases peripheral blood samples were used for FISH analysis and IHC was carried out on bone marrow biopsies. Cases were selected on the basis of whether FISH and IHC were analysed at the same time point. Deletions of TP53 (17p13) were detected by FISH (Vysis); a threshold of &gt;20% of cells with p53 deletion was considered clinically significant. For IHC detection a monoclonal antibody (clone BP53-12, Novocastra) was used. Cases were considered positive when p53 stained the majority of lymphocyte nuclei, those cases with few or weakly positive cells in proliferation centres were considered negative. Correlation with FISH (&gt;20% deleted cells) and IHC showed 69 cases (75%) negative for both assays and 6 cases (7%) positive for FISH and IHC. The remaining 17 cases (18%) showed discordant results; 6 cases showed TP53 deletion &gt;20% by FISH but showed no p53 overexpression by IHC, 4 cases had overexpression of p53 and no TP53 deletion, 3 cases had p53 overexpression with TP53 deletion between 10–20%, and 4 cases showed TP53 deletion between 10–20% but no overexpression of p53. This is compatible with a sensitivity of 50% and specificity of 91%. In order to understand the mechanism better, mutation analysis of TP53 gene will be done in discordant cases. All patients positive for both results and a minority of patients (16%) with no p53 abnormalities detected by FISH or IHC were refractory to Fludarabine. Within the discordant group, most of refractory patients (67%) were found in cases with p53 overexpression and TP53 deletion between 10–20%. In conclusion, the combination of both methods (FISH and IHC) may be useful to identify CLL cases with an adverse prognosis and non responders to Fludarabine. A large study with more cases is necessary to clarify the underlying mechanisms involved in those cases with p53 overexpression without TP53 deletion.

The Use of Low-Dose Alemtuzumab as Single Agent in the Treatment of Complication in Advanced Chronic Lymphocytic Leukaemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4212-4212
Author(s):  
Luca Laurenti ◽  
Michela Tarnani ◽  
Idanna Innocenti ◽  
Silvia De Matteis ◽  
Simona Sica ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Peripheral Blood ◽  
Low Dose ◽  
Lymphocytic Leukaemia ◽  
Single Agent ◽  
Previous Treatment ◽  
High Dose ◽  
End Of Treatment ◽  
Hb Concentration ◽  
Cmv Reactivation

Abstract There are some report in literature about the use of Alemtuzumab in patients affected by advanced B-cell chronic lymphocytic leukaemia who developed severe transfusion-dependent autoimmune haemolytic anaemia (AIHA) resistant to conventional therapy or cutis involvement. We report the use of low-dose Alemtuzumab in 4 AIHA patients and in 1 case of eyelid leukaemia cutis. Alemtuzumab was given subcutaneously at 10 mg three times weekly for 30 administrations (10 weeks). Treatment was stopped for progression disease, grade IV thrombocytopenia and/or infections or Cytomegalovirus (CMV) reactivation. Prophylaxis consiste on co-trimoxazole and aciclovir from the start of the treatment until 2 months after the end of treatment. Peripheral blood count, biochemical screening, antigenemia and CMV DNA analysis, reticulocyte count were conducted weekly. DAT and IAT were studied every two weeks during the treatment. Patient with eyelid leukaemia cutis underwent to histological examination before and after the end of treatment. AIHA response, was defined as the independence from RBC transfusion and a concomitant &gt; 2.0 g/dl rise in Hb concentration. Four male patients developed DATpositive AIHA at a median of 44.5 months from the B-CLL diagnosis. Previous treatment for B-CLL, stage and haemoglobin (Hb) values at Alemtuzumab administration are shown in table 1. Three patients underwent to RBCu transfusion before Alemtuzumab treatment, and one also during the treatment (2RBCu). The median haemoglobin value at first Alemtuzumab administration was 8.25 gr/dl. (table1) Two patients showed CMV reactivation at 5th and 6th week of therapy and were treated with oral ganciclovir for 14 and 21 days respectively. AIHA response was reached at median of 7 weeks of Alemtuzumab therapy in all patients while the median duration time of response to Alemtuzumab therapy was 10 months. Two patients underwent to further treatment for DAT negative progressive disease after 9 and 10 months from the end of Alemtuzumab therapy respectively, one patients was treated after 26 months for AIHA relapse, while the last patients even if showed AIHA remission is currently at 6th week of Alemtuzumab treatment (Hb 8g/dl). At the end of Alemtuzumab administrations the median Hb concentration was 12.7 g/dl regarding clinical responses, the patient no.1 obtained SD, the other 2 PR. Patient with leukemia cutis (LC) showed a constant reduction of eyelid involvement until clinical resolution after 240 mg of Alemtuzumab. Now a day, a manteinance therapy is ongoing with Alemtuzumab 30 mg monthly maintaining complete remission of eyelid localization and partial remission of CLL 10 months after induction therapy. In All patients the therapy has been well tolerated, with mild haematological and extra-haematological side effects (grade I). No episode of febrile neutropenia or bacterial/fungal infection occurred during the treatment. Our data confirmed the literature data about the use of Alemtuzumab, even if with low-dose, as salvage treatment for transfusion-dependent and resistant AIHA in pre-treated B-CLL patients and show a new indication for LC involvement. Table 1: Patient’s clinical characteristics Age/Sex Binet/Rai Stage Months from B-CLL diagnosis and AIHA/LC Previous treatment for B-CLL (number of cycles) Biological Parameter Months between last B-CLL therapy-AIHA/LC Hb at baseline Alemtuzumab treatment (gr/dl) DAT/IAT 68/M C/IV 9 CHOP(6), CVP(3) Unmutated IgVH&#x2028; Zap-70 +&#x2028; CD38 +&#x2028; Del17p 1 9.4 DAT 4+&#x2028; (IgG 4+)&#x2028; IAT 4+ 53/M C/IV 31 Chl/Pdn(6), FC(6), Pdn(6), Ig, Splenectomy Mutated&#x2028; Zap-70 −&#x2028; Normal karyotipe 3 7.1 DAT 2+&#x2028; (IgG 1+)&#x2028; IAT 2+ 46/M C/III 58 CHOP(8), HD-CTX, aPBSCT Unmutated IgVH&#x2028; Normal Kariotype 38 10.1 DAT 4+&#x2028; (IgG 3+; C3d 1+)&#x2028; IAT − 56/M C/IV 64 FC, chl, fludarabine, RIC transplant Unmutated IgVH Zap-70 + CD38 −Del 17p, Del 13q 28 4.9 DAT 4+&#x2028; (IgG 4+)&#x2028; IAT 2+ 61/M B/II 108 Fludarabine, CHOP, INFa, chl/pdn Mutated IgVH&#x2028; Zap-70 +&#x2028; CD38 +&#x2028; Del 17p, +12 24 14.3 Negative M: male, Chl: chlorambucil, Pdn: prednisone, FC: fludarabine+cyclophosphamide, Ig: intravenous immunoglobulin, HD-CTX: high dose-cyclophosphamide, aPBSCT: autologous peripheral blood stem cell transplantation.

A living systematic review of immune checkpoint inhibitors in cancer patients: A novel platform for evidence synthesis in oncology.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6596-6596
Author(s):  
Irbaz Bin Riaz ◽  
Rabbia Siddiqi ◽  
Saad Malik ◽  
Elizabeth Jane Cathcart-Rake ◽  
Ognjen Gajic ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Clinical Decision Making ◽  
Checkpoint Inhibitors ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Single Agent ◽  
Phase 2 ◽  
New Evidence

6596 Background: Several previous systematic reviews and meta-analyses have attempted to summarize toxicity of Immune checkpoint inhibitors (ICIs). However, very soon after each one of these reviews has been published, it became outdated. ICIs are currently used in 14 different cancers and data is rapidly evolving from new clinical trials. A living Systematic review, which is defined as a systematic review that is continually updated to incorporate relevant new evidence as it becomes available, is necessary in this situations. Therefore, we performed an updated systematic review and a meta-analysis which will serve as a foundation of a living Systematic review. Methods: MEDLINE, EMBASE and Cochrane were searched to identify phase 2 and 3 RCTs of PD-1/PD-L1 ICIs. Included studies compared either immunotherapy alone or combination with existing standard of care treatment and reported data for AE’s of interest. DerSimonian-Laird random effects Meta-Analysis was performed to derive pooled odds Ratio (OR) estimates for AE’s of interest. An infrastructure of a living systematic review is being developed and it includes monthly literature searches, cumulative meta-analysis and an online reporting platform. Results: We screened 6746 studies and 31 phase 3 and 2 phase 2 RCTs (n = 21,421) were included in the analysis. 22 RCTs used PD-1/PD-L1 ICIs as a single agent and 11 as a combination therapy. Selected toxicity estimates are summarized in a table. Conclusions: The meta-analysis updates previously published toxicity estimates and provides additional information about the risk of toxicities in single versus combination regimens. We have initiated the first living systematic review in oncology that will be continuously updated, incorporating relevant new evidence as it becomes available, and will provide accurate and up to date toxicity estimates to support clinical decision making. [Table: see text]

Comparative efficacy of chemoimmunotherapy versus immunotherapy alone in the front-line treatment of advanced non-small cell lung cancer: A systematic review and network meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9552-9552
Author(s):  
Ranjan Pathak ◽  
Gilberto Lopes ◽  
Han Yu ◽  
Wenyan Ji ◽  
Madan Aryal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Single Agent ◽  
Comparative Efficacy ◽  
Front Line ◽  
Phase 3 ◽  
Significant Difference ◽  
Prospective Trials ◽  
Nsclc Patients

9552 Background: Immune checkpoint inhibitors (ICI) and combination chemotherapy (chemo) plus ICI (Chemo-ICI) have been shown in RCTs to have improved OS compared to chemo in the 1L treatment of advanced NSCLC. However, the benefit of chemo-ICI compared with ICI alone is unknown. Methods: Systematic review using MEDLINE, Embase and Cochrane CENTRAL was done to identify relevant studies up to December 2019. Phase 3 RCTs that evaluated the efficacy of 1L ICI or chemo-ICI and reported outcomes stratified by PD-L1 status (<1%, 1-49%, ≥50%) were included. ICI was defined as single-agent PD-1 axis inhibitor or dual checkpoint blockade with PD-1 axis inhibitor plus CTLA-4 inhibitor. Comparison for PD-L1<1% included chemo-ICI vs ipi/nivo and for PD-L1 1-49% and PD-L1>50% included chemo-ICI vs ipi/nivo or single-agent ICI. OS, PFS, and ORR were extracted. Network meta-analysis (NMA) was done in Bayesian random-effects regression models. Results: Ten phase 3 RCTs (7971 screened) involving 7,218 patients assigned to ICI (pembro or atezo or ipi/nivo) or chemo-ICI (platinum-doublet + atezo, pembro, or nivo) were included. In PD-L1 <1% patients, NMA comparing chemo-ICI with ipi/nivo failed to show a statistically significant difference in OS, PFS or ORR. In PD-L1 1-49% patients, there was no significant difference between chemo-ICI vs ICI in OS or ORR; PFS could not be analyzed due to lack of available data. In PD-L1 >50% patients, chemo-ICI was associated with improved PFS and ORR compared to ICI alone, but without any OS difference (Table). Conclusions: Although the addition of chemo to ICI appears to improve ORR and PFS in PD-L1 ≥50% patients when compared to ICI alone, chemo-ICI does not confer an OS benefit in the 1L treatment of NSCLC patients regardless of PD-L1 status. Prospective trials comparing chemo-ICI, ICI monotherapy, and combination ICI are needed to confirm these findings. OS, PFS and ORR with chemo-ICI vs ICI. [Table: see text]

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