Treatment with Idelalisib in Patients with Relapsed or Refractory Follicular Lymphoma: The Observational Italian Multicenter FolIdela Study

Abstract

Follicular lymphoma (FL) is an indolent hematological disease, often responsive to the first line of treatment, but characterized by repeated relapses. The therapeutic algorithm for relapsed/refractory FL patients comprises phosphatidylinositol 3-kinase inhibitors. Idelalisib showed anticancer activity, while inducing a significant rate of toxicities. Since the evidence in the literature on its use in normal clinical practice is scarce, a retrospective multicenter study was conducted to evaluate effectiveness and tolerability in a real-life context. Seventy-two patients with a median age at diagnosis of 57.2 years—mostly with an advanced stage (88.9%) and relapsed to the most recent therapy (79.1%)—were enrolled. The median number of prior therapies was three (20.8% refractory to the last therapy before idelalisib). With a median number of 4 months of treatment, the overall response rate was 41.7% (20.8% complete responses). Median disease-free survival and overall survival were achieved at 8.4 months and at 4 years, respectively. Forty-four percent of patients experienced at least one drug-related toxicity: 6.9% hematological ones and 43% non-hematological. The study confirmed that idelalisib has anticancer effectiveness and an acceptable safety profile in relapsed/refractory FL with unfavorable prognostic characteristics, even in the context of normal clinical practice.

Real‐life efficacy and safety of idelalisib in 55 double‐refractory follicular lymphoma patients

“…The development of side effect related to idelalisib resulted in a dose reduction to 100 mg twice a day in seven patients, to 100 mg/day and subsequent discontinuation of therapy in six patients, and permanent discontinuation in five patients. This is in line with the discontinuation rate reported in the literature, which approximates 20% 6,9,10 …”

“…In 28 patients therapy had to be discontinued: in 13 patients due to lack of response, in 11 due to adverse events occurring during treatment, in four due to the use of idelalisib as a bridge to transplantation. The main reason for therapy discontinuation was disease progression, similarly to what has been reported in the literature 6,9,10 …”

“…It is important to underline that ORR in the present study was 73%, comparing favourably with the 55.6%, 57% and 41.7% of the DELTA trial, 6 the English 9 and the Italian 10 real‐life experiences. Given the high heterogeneity of the few studies reported in the literature, it is difficult to argue why our patients performed better with respect to the other experiences, and chance cannot be ruled out.…”

“…This is in line with the discontinuation rate reported in the literature, which approximates 20%. 6,9,10 In our series, the median exposure to idelalisib was 10 months. In 28 patients therapy had to be discontinued: in 13 patients due to lack of response, in 11 due to adverse events occurring during treatment, in four due to the use of idelalisib as a bridge to transplantation.…”

“…This is in agreement with an English real‐life experience, 9 which showed 44% of patients still receiving therapy by the time of the last follow‐up. On the contrary, the DELTA 6 trial and a recent Italian retrospective study 10 reported a significantly higher discontinuation rate, with less than 15% of patients still receiving idelalisib at the latest available follow‐up.…”