Idelalisib Monotherapy and Durable Responses in Patients with Relapsed or Refractory Small Lymphocytic Lymphoma (SLL)

• Published in: Blood 2015-12, Vol.126 (23), p.2743-2743
• Main Authors: Gopal, Ajay K, Davies, Andrew John, Flinn, Ian W., Ghia, Paolo, Goy, Andre, Salles, Gilles A., Abella, Steve, Philip, Betsy, Sorenson, Bess, Wagner-Johnston, Nina D.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.2743.2743

Background: SLL, a subtype of indolent non-Hodgkin's Lymphoma (iNHL), is considered the tissue equivalent of chronic lymphocytic leukemia (CLL); each disease is considered a clinical variation of the same biological entity. SLL is characterized by the accumulation of small, mature lymphocytes in lymph nodes without elevation of peripheral blood lymphocytes. SLL is an uncommon disorder, comprising 6% of cases of NHL and 15% of cases of the CLL/SLL entity.SLL is often diagnosed at an advanced stage, and patients (pts) with relapsed or refractory (R/R) disease are at risk for poor prognosis. Idelalisib (IDL) is a selective oral PI3Kδ inhibitor. IDL monotherapy (IDL-mono) demonstrated considerable anti-tumor activity in pts with R/R iNHL in phase 1 Study 101-02 (Study 02; NCT00710528), and phase 2 Study 101-09 (Study 09; NCT01282424; Gopal et al. NEJM. 2014;370:1008-1018). This post hoc analysis evaluated efficacy and safety in pts with SLL who were treated with IDL in Study 02 or Study 09. Methods: Eligible pts with SLL included those with R/R disease treated with IDL-mono across 7 dose cohorts in Study 02, and those with double-refractory disease (to both rituximab and an alkylating agent) treated with IDL-mono in Study 09. The primary objectives for Study 02 were to evaluate the safety and pharmacokinetics of IDL in pts with R/R hematologic malignancies. The primary objectives for Study 09 were to evaluate the efficacy and safety of IDL in pts with R/R B-cell iNHL. In both studies, IDL was continued until disease progression (PD) or unacceptable toxicity. Clinical response was assessed with the use of standard criteria for lymphoma (Cheson et al. J Clin Oncol. 2007;25:579-586). Results: A total of 39 pts with R/R SLL participated in the 2 trials.Study 02 enrolled 11 pts, (5 on IDL doses ˂100 mg BID; 6 on IDL doses ˃100 mg BID). Study 09 enrolled 28 pts who received IDL 150 mg BID. Enrolled pts (Study 02 and Study 09) had a median age of 69 and 65 years [range 34-87], and 73% and 75% were male, respectively. In both studies, 82% of pts presented with Ann Arbor Stage IV disease at baseline and had received a median of 4 prior regimens [range 1-9]. In Study 02, 9 of the 11 pts (82%) had refractory disease; all 11 pts had received prior regimens containing fludarabine. In Study 09, 27 of the 28 pts (96%) were refractory to both rituximab and an alkylating agent; common previous therapy included: 28/28 rituximab, 25/28 cyclophosphamide, 21/28 bendamustine, 19/28