scholarly journals Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma

Blood ◽  
2014 ◽  
Vol 123 (22) ◽  
pp. 3406-3413 ◽  
Author(s):  
Ian W. Flinn ◽  
Brad S. Kahl ◽  
John P. Leonard ◽  
Richard R. Furman ◽  
Jennifer R. Brown ◽  
...  

Key Points This clinical study assessed idelalisib, a selective PI3Kδ inhibitor, in 64 patients with relapsed, indolent non-Hodgkin lymphoma. Idelalisib treatment rapidly induced durable disease responses in heavily pretreated patients with a favorable safety profile.

Blood ◽  
2014 ◽  
Vol 123 (22) ◽  
pp. 3398-3405 ◽  
Author(s):  
Brad S. Kahl ◽  
Stephen E. Spurgeon ◽  
Richard R. Furman ◽  
Ian W. Flinn ◽  
Steven E. Coutre ◽  
...  

Key Points This clinical study assessed idelalisib, a selective PI3Kδ inhibitor, in 40 patients with relapsed/refractory MCL. In a dose-escalation trial in heavily pretreated patients, an overall response rate of 40% was observed with an acceptable safety profile.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4958-4958
Author(s):  
Emi Noguchi ◽  
Rumiko Okamoto ◽  
Tatsu Shimoyama ◽  
Eisaku Sasaki ◽  
Yasushi Omuro ◽  
...  

Abstract BACKGROUND: The treatment of relapsed or refractory Non-Hodgkin lymphoma (NHL) depends on the number of drugs of choice, and additional treatments can achieve remission for many patients. Cladribine (2-chlorodeoxyadenosine, 2-CdA) is a purine nucleoside analogue, and generally approved for indolent NHL relapsed after or refractory to previous chemotherapy. We conducted this analysis to determine efficacy and toxicity of 2-CdA in the treatment of relapsed or refractory NHL. PATIENTS AND METHODS: 29 relapsed or refractory NHL patients treated with cladribine in a single institution from 2002 to 2007 were entered in a retrospective analysis. RESULTS: The median age was 64 years. Seventeen patients (59%) were male, twenty (69%) with indolent lymphoma consisting mainly of follicular lymphoma and mantle cell lymphoma, and twenty-eight (97%) previously treated with 1 to 10 regimens (mean 2.7). Cladribine was administrated 24% as a monotherapy and 22% with other chemotherapeutic agents. The dose and duration of administration were variable among the patients, however, most common regimen was 0.9mg/kg/day for seven consecutive days, for 1 to 6 cycles, depending on response. Response rate was 72% (CR and PR were 31%, 41%, respectively). Median overall survival was of 2.9 years. Patients showed improved survival rate in performance status 0 or 1 (Willcoxon: P<0.0001, Log-rank: P<0.0001), more than 3 cycles of cladribine (Willcoxon: P<0.028, Log-rank: P=0.126), or combination chemotherapy (Willcoxon: P=0.042, Log-rank: P=0.040). Main reason for death was disease progression. Myelosuppression was the most common adverse effect. Eight patients (28%) experienced CTCAE grade 4 neutropenia, fourteen (48%) lymphocytopenia, and three (10%) thrombocytopenia, respectively. Two episodes (6.9%) of grade 3–4 infections were observed. There was no treatment related mortality. CONCLUSIONS: Cladribine is effective even in heavily pretreated patients with NHL. It also has favorable safety, and can be considered as a good alternative treatment for relapsed or refractory NHL.


Cancer ◽  
2009 ◽  
Vol 115 (15) ◽  
pp. 3475-3482 ◽  
Author(s):  
M. A. Rodriguez ◽  
Robert Pytlik ◽  
Tomas Kozak ◽  
Mukesh Chhanabhai ◽  
Randy Gascoyne ◽  
...  

2016 ◽  
Vol 1 (2) ◽  
pp. 122-131 ◽  
Author(s):  
Sven de Vos ◽  
Nina D. Wagner-Johnston ◽  
Steven E. Coutre ◽  
Ian W. Flinn ◽  
Marshall T. Schreeder ◽  
...  

Key Points Combining phosphatidylinositol-3-kinase δ inhibition with rituximab, bendamustine, or both is feasible and active in relapsed iNHL. The safety of novel combinations should be proven in phase 3 trials before adoption in clinical practice.


Blood ◽  
2014 ◽  
Vol 123 (22) ◽  
pp. 3390-3397 ◽  
Author(s):  
Jennifer R. Brown ◽  
John C. Byrd ◽  
Steven E. Coutre ◽  
Don M. Benson ◽  
Ian W. Flinn ◽  
...  

Key Points Idelalisib was evaluated in 54 patients with heavily pretreated chronic lymphocytic leukemia, and target inhibition was documented in vivo. Oral idelalisib therapy demonstrated a favorable safety profile and rapidly induced durable disease control in the majority of patients.


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