Real-Word Clinical Management of Patients Treated with Idelalisib in France: A Study of 529 Cases of Chronic Lymphocytic Leukemia (CLL) and Follicular Lymphoma (FL)
Authors: Michallet Anne-Sophie , Gyan Emmanuel , Feugier Pierre , Nunes Ana , Abdelhadi Tarek , Ysebaert Loic , Leprêtre Stéphane 
Published: October 2019

Abstract
Introduction:
Idelalisib (IDELA), the first PI3K delta inhibitor, is indicated in Europe in combination with rituximab (R) or ofatumumab for the treatment of adult patients (pts) with CLL and as monotherapy for the treatment of adult pts with refractory FL. IDELA provides an important therapeutic option for the management of CLL and FL, but there are few real word data on its effectiveness and safety. The objective of this study was to describe the management of IDELA therapy in a real word setting in France for patients with CLL or FL.
Methods:
This multi-center retrospective clinical practice survey started in February, 2017 and ended in July, 2017. During this period, 52 physicians agreed to complete a questionnaire collecting data for each pt they have treated with IDELA according to the marketing authorization label: demographic, clinical and biological pt characteristics at the time of IDELA initiation; pt follow-up modalities including nurse and pharmacist consultations; conditions of IDELA use; duration of treatment; reasons for discontinuation; and treatment administered before and after IDELA discontinuation. Analyses were conducted separately in CLL and FL groups and data are presented descriptively.
Results:
The 52 participating physicians were geographically well distributed and were mostly located at regional hospitals (44%) or university hospitals (38%). Data on 529 pts were collected, including 384 CLL pts (20.1% 1L, 33.9% 2L, 46% 3L+) and 145 FL pts (60.7% 3L, 26.9% 4L, 12.4% 5L+), of whom 61% and 63% respectively were still on treatment at the time of the survey. For CLL/FL respectively, median age was 69 y/68 y, 27.6%/24.8% were aged > 75 y, 76.7%/72.0% were ECOG 0-1, median number of comorbidities was 1.0 for both CLL and FL with hypertension as the most common and median prior therapies was 2 in both groups. For CLL pts, 65.1% had disease stage Binet C and most had poor prognostic markers (14.6% del(11q), 44.0% del(17p) and 19.7% TP53 mutation). IDELA was initiated, at 150 mg BID in 90.6%/93.8% of CLL/FL pts respectively. Median duration of treatment was 24.0 months for overall CLL and not reached in del(17p)/TP53m sub-group and in FL group. Independent predictors of longer treatment duration were ECOG ≤ 1, prophylaxis against Pneumocystis jirovecii Pneumonia (PJP) or cytomegalovirus (CMV) infections and consultation with a nurse at initiation of treatment in the CLL group and ECOG score ≤ 1 in the FL group (Table 1, 2). Most of CLL/FL pts respectively had a nurse consultation at the start of IDELA (68.0%/56.6%) and prophylaxis for PJP or CMV (93.0%/77.0%). Sixty nine percent of pts in each group were tested for CMV before starting IDELA. In CLL/FL groups respectively, 61 pts (15.9%)/22 pts (15.2%) had at least one IDELA dose interruption. Diarrhea was the main reason for interruption (G1-2: 28%/11%, G3-4: 21%/21%) followed by neutropenia (30%/18%), pneumonia (11%/25%, non-infectious: 1%/7%) and ALT/AST elevation (6%/14%). IDELA was permanently discontinued in 152 CLL pts/54 FL pts respectively, mainly for disease progression (34%/41%), diarrhea G3-4 (16%/6%), diarrhea G1-2 (4%/2%), remission or good response (9%/19%), pneumonia (9%/13%, non-infectious: 3%/7%), neutropenia and ALT/AST elevation (5%/2% each). Of 151 CLL pts/54 FL pts who permanently discontinued IDELA, 83 (55%)/34 (63%) received subsequent treatment, mainly ibrutinib monotherapy (70%) in the CLL group and chemotherapy combined with anti-CD20 (63%) in the FL group.
Conclusion:
This large clinical practice survey provides useful information about the management of IDELA treatment across France and permits factors predictive of treatment duration to be identified. Most FL pts had advanced disease and most CLL pts had genetic markers of poor prognosis. Safety was in accordance with the known safety profile of IDELA. PJP prophylaxis contributed to longer duration of treatment in CLL and should be prescribed to all pts receiving IDELA. Consultation with a nurse before and during treatment helps manage CLL and FL pts treated with IDELA and can prolong duration of treatment.

Disclosures
Feugier: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nunes:Gilead Sciences: Employment. Abdelhadi:Gilead Sciences: Employment. Ysebaert:Roche: Consultancy, Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.