Efficacy and Safety of Phosphoinositide 3-Kinase (PI3K) Inhibitors in Non-Hodgkin's Lymphoma: A Systematic Review and Meta-Analysis

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.12-13
• Main Authors: Khan, Sana Irfan, Anwar, Muhammad Yasir, Rafae, Abdul, Khan, Anam, Khan, Atif Irfan, Aamir, Sobia, Batool, Syeda Sabeeka, Tameez Ud Din, Asim, Khan, Israr, Javaid, Anum, Qadeer, Haifza Abeera, Ahmed, Zahoor, Gul, Rohail, Aijaz, Zobia, Anwer, Faiz
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-134986

Background: Phosphatidylinositol-3-Kinase (PI3K)-oncogenic protein kinase is ubiquitously expressed in cells, however, PI3Kδ and PI3Kγ are selectively expressed in hematopoietic cells predominantly in leucocytes. Suppression of the PI3K pathway has emerged as a therapeutic strategy for non-Hodgkin lymphoma (NHL) and 3 PI3K inhibitors are already approved for therapeutic use with many others under exploration. The application of these agents in terms of risk and benefit remains scarcely explored. Therefore, a systematic review and meta-analysis was conducted to assess the efficacy and safety of PI3K inhibitors in non-Hodgkin lymphoma. Methods: A comprehensive literature search was conducted from inception to the 4th of April 2020, following PRISMA guidelines on 4 databases (PubMed, Cochrane library, clinicaltrials.gov, web of science, and Embase). A search was performed without the use of filters and the MeSH terms used were “lymphoma, non-Hodgkin” and “phosphoinositide-kinase inhibitors”. Only studies with available data that were either completed or still recruiting were included. Trials with no reported efficacy or safety data were excluded. A pooled analysis of the extracted data was performed using the “meta” package by Schwarzer et al. in the R programming language (version 4.0.2). For data analysis purposes, in the case of multi-arm studies, only those cohorts where PI3K was administered were included. The event rates were pooled using the inverse variance method and logit transformation. The between-studies variance was calculated using the DerSimonian-Laird estimator. The random-effects model was used for the analysis. Results: Initial search revealed 391 articles. After a thorough screening, 22 studies involving 1123 patients with relapsed or refractory NHL that fulfilled the inclusion criteria were included (Table 1). The median age ranged from 58-70 years. The median number of prior therapies ranged from 2 to 4. Twenty studies used a selective PI3K inhibitor including voxtalisib, pilaralisib, umbralisib, duvelisib, idelalisib, copanlisib, buparlisib, and parsaclisib. The pooled overall response rate (ORR) was 50% [95% CI: 42%; 58%] with pooled complete response of 15% [95% CI: 12%; 20%]. A subgroup analysis was performed on complete responses (CR) of patients with diffuse large B cell lymphoma (DLBCL), and follicular lymphoma (FL). The CR in FL and DLBCL were 20% [95% CI: 15%-20%] and 14% [95% CI 8%-25%] respectively, and the difference between