ZEUS
Research type
Research Study
Full title
Non-interventional study to assess the safety profile of idelalisib in patients with refractory follicular lymphoma (FL)
IRAS ID
242585
Contact name
Ruth Pettengell
Contact email
Sponsor organisation
Gilead Sciences Europe Ltd.
Clinicaltrials.gov Identifier
EUPAS19618, EU PASS Reg No
Duration of Study in the UK
2 years, 10 months, 30 days
Research summary
Summary of Research
This is a Non-Interventional Study looking at the safety profile of Idelalisib in patients with refractory follicular lymphoma. It is a post authorization safety study, requested by the Pharmacovigilance Risk Assessment committee (PRAC) or the European Medicines Agency. The present study will evaluate data collected since the authorisation of this medication in the EU in September 2014. Part of the study will involve retrospective data collection and part will involve collection of data while the patient is medicated under the local standard of care.
Summary of Results
This study was conducted to ascertain the risk-benefit balance of idelalisib monotherapy for the treatment of patients with refractory follicular lymphoma. The study population corresponds to the usual profile of later line Follicular Lymphoma patients (i.e., elderly, heavily pre-treated with advanced disease). Within the treatment period and the first month of follow-up, 96% of patients had experienced an Adverse Event and 10.9% had died.
The majority of patients (70.4%) received 150 mg dose of idelalisib with a median duration of exposure to idelalisib of 6.7 months. The duration of exposure, patient demographics and disease characteristics of this refractory Follicular Limphoma population were comparable to the registrational Study 101-09. As is the case with Study 101-09, subjects in this study were drawn from a patient population that was highly refractory and heavily pretreated with a median of 3 therapies.
The occurrence for Health Outomes of Interest ≥ grade 3 infections was 11.7% and for Health Outomes of Interest ≥ grade 3 diarrhea and/or colitis was 7.3%, which was slightly lower than observed in the registration Study 101-09, 26.4% and 19.2% respectively. Serious Adverse Events were reported in about half of the patients and Treatment Emergent Adverse Events were consistent with Study 101-09. Permanent discontinuation of idelalisib due to reatment Emergent Adverse Events was 71.7% (which includes disease progression and lack of efficacy, in addition to Adverse Events). This value is inflated, though, as some sites entered progressive disease or lack of efficacy as an Adverse Event term. In other words, patients who were determined to have discontinued idelalisib due to an Adverse Event could have experienced an Adverse Event, progressive disease, or lack of efficacy. From Subject Disposition, approximately 39.3% of patients discontinued idelalisib due to an Adverse Event, which is higher than the 28% reported in Study 101-09. However, it is important to note that the current study was conducted using real-world data, while Study 101-09 was a Phase 2 clinical trial of a relatively new molecule. Clinical trials often have strict selection criteria, making it difficult to generalize the findings to the real-world population of patients who might receive the intervention of interest.
The overall response rate (ORR) in the efficacy evaluable (n=198) study population was 57.6% which was remarkably similar to that was observed in the registrational Study 101-09 (57.6%) (Wagnor-Johnston 2019). In this highly refractory population, idelalisib demonstrated a clinically meaningful PFS of 12.2 months, consistent with the 11.0 months Progression Free Survival reported at the 6-year follow-up of Study 101-09. In the current study, median Overal Survival was not reached which is unsurprising given the limited follow-up for survival in this study; the observed median Overal Survival for the registrational study 101-09 was greater than 5 years (61.2months).Conclusion:
The conclusions for the study are as follows:
Safety:
A large proportion of patients experienced Adverse Events due to idelalisib.
The majority were grade ≥3 and related to idelalisib therapy.
No new safety signals were observed
In general, the safety findings are similar to those in the registrational study 101-09 and representative of the established safety profile of idelalisib in an older, previously treated, highly refractory Follicular Limphoma population.Effectiveness:
oIdelalisib was effective in the FL population (ORR= 57.6%).
18.7% of the patients achieved a CR, while 38.9% of the patients achieved a PR.
In this highly refractory and heavily pre-treated population, patients receiving idelalisib achieved a clinically meaningful Progression Free Survival (Kaplan Meier, estimate of 12.2 months) and median survival was not reached. The Duration Of Response was approximately 21.9 months.These findings corroborate those from the registrational study (Study 101-09) of idelalisib in patients with relapsed/ refractory follicular lymphoma and demonstrate that the overall risk-benefit balance remains favorable in this patient group who have limited treatment options.
REC name
South Central - Hampshire B Research Ethics Committee
REC reference
18/SC/0255
Date of REC Opinion
12 Jun 2018
REC opinion
Further Information Favourable Opinion