Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party

Johannes Schetelig,Dietrich Beelen,Stéphanie Nguyen Quoc,Nicolaus Kröger,Jörg Bittenbring,Gèrard Socié ,Catherine Thiéblemont ,Stéphane Leprêtre ,Ronjon Chakraverty,Jiřı́ Mayer ,Noël Milpied ,Paul Browne,Patrice Chevallier,Paneesha Shankara,Julio Delgado,Olivier Hermine,Ibrahim Yakoub‐Agha ,Sylvette Maury ,Olivier Tournilhac,Michel Van Gelder,Liesbeth C De Wreede,Eric Deconinck,Arne Brecht,Mathilde Hunault‐Berger ,Henning Baldauf,Jennifer Hoek,Michele Malagola,Ghandi Damaj,Peter Dreger

doi:10.1038/s41409-020-01069-w

Abstract

No studies have been reported so far on bridging treatment with idelalisib for patients with chronic lymphocytic leukemia (CLL) prior to allogeneic hematopoietic cell transplantation (alloHCT). To study potential carry-over effects of idelalisib and to assess the impact of pathway-inhibitor (PI) failure we performed a retrospective EBMT registry-based study. Patients with CLL who had a history of idelalisib treatment and received a first alloHCT between 2015 and 2017 were eligible. Data on 72 patients (median age 58 years) were analyzed. Forty percent of patients had TP53mut/del CLL and 64% had failed on at least one PI. No primary graft failure occurred. Cumulative incidences of acute GVHD °II–IV and chronic GVHD were 51% and 39%, respectively. Estimates for 2-year overall survival (OS), progression-free survival (PFS), and cumulative incidences of relapse/progression (CIR) and non-relapse mortality NRM were 59%, 44%, 25%, and 31%. In univariate analysis, drug sensitivity was a strong risk factor. For patients who had failed neither PI treatment nor chemoimmunotherapy (CIT) the corresponding 2-year estimates were 73%, 65%, 15%, and 20%, respectively. In conclusion, idelalisib may be considered as an option for bridging therapy prior to alloHCT. Owing to the high risk for acute GVHD intensified clinical monitoring is warranted.

Highlights

Pathway inhibitors (PI) such as BTK-inhibitors (BTKi), PI3Kinase inhibitors (PI3Ki), and BCL2-inhibitors (BCL2i) have fundamentally transformed the standard treatment landscape for chronic lymphocytic leukemia (CLL) in recent years
EBMT registrybased study allow for a discussion of the risk-benefit ratio of idelalisib as a bridging treatment prior to allogeneic hematopietic cell transplantation (alloHCT) and— from a broader perspective—to reason about contemporary indications for alloHCT for CLL
Safety of idelalisib treatment prior to alloHCT has been a concern due to the observation of autoimmune-mediated diseases, resulting in severe colitis, pneumonitis, and hepatitis, which may occur during idelalisib treatment [8]

Summary

Introduction

Pathway inhibitors (PI) such as BTK-inhibitors (BTKi), PI3Kinase inhibitors (PI3Ki), and BCL2-inhibitors (BCL2i) have fundamentally transformed the standard treatment landscape for chronic lymphocytic leukemia (CLL) in recent years. Since these drugs target different signaling pathways, CLL is usually not cross-resistant to different PIs. PIs can be administered sequentially [1,2,3,4]. Patients who had received idelalisib for CLL prior to alloHCT have not been studied systematically so far. We analyzed the outcome of patients with CLL who had received idelalisib prior to alloHCT. We report final results from this EBMT registry study

Study design and patient eligibility

Results

Transplant procedure

Discussion

Compliance with ethical standards