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Prevalence of BTK and PLCG2 Mutations in CLL Patients relapsing under Ibrutinib

This study aims to determine the prevalence of BTK and PLCG2 mutations in chronic lymphocytic leukemia (CLL) patients who relapsed or responded to ibrutinib treatment outside of clinical trials. The study is international, retrospective, observational, and multicenter.

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Prevalence of BTK and PLCG2 Mutations in CLL Patients relapsing under Ibrutinib

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  1. Mannheim, February 12, 2019 16. ELN Symposium Prevalence of BTK and PLCG2 Mutations in CLL Patients relapsing under Ibrutinib • Lydia Scarfò e Silvia Bonfiglio (Università Vita-Salute San Raffaele, Milano, Italy) • Lesley Ann Sutton (Karolinska Institut, Stockholm, Sweden)

  2. Study Design International, retrospective, observational, multicenter study PRIMARY OBJECTIVE: To determine the prevalence of BTKand PLCG2 mutations in CLL patients relapsing or responding to ibrutinib outsideclinical trials • CLL patients who received ibrutinib treatment at full dose without >14 days interruption* • Relapsedcases: relapse on ibrutinib according to the modified IwCLL 2008 criteria • Responders: responding to ibrutinib according to the modified IwCLL 2008 criteria and have samples collected after at least 1 year of treatment • Patients with Richter Transformation were excluded* • *a total of 23 patients have been excluded for either reasons

  3. Participanting Sites Up to 22 sites, 18 already sent samples * MTA to be finalized; #waiting for sample shipment

  4. Update (8Feb2019) * 2 UK; 3 Sweden; 2 Denmark; 1 Russia

  5. Methods • DNA extraction from purified B cells • Agilent HaloPlexHS kit (BTK and PLCG2 all exons) • Paired-end sequencing (NextSeq Illumina) • Variant allelic frequency (VAF) cutoff of 1% (Targeted deep sequencing) BTK PLCG2

  6. Thank you all Paolo Ghia, Lesley Ann Sutton, Silvia Bonfiglio, Richard Rosenquist • Università Vita-Salute San Raffaele, Milan Antonella Capasso, Pamela Ranghetti • University of Eastern Piedmont, Novara, Italy: Gianluca Gaidano, Riccardo Moia, Clara Deambrogi • University of Padua, Padua, Italy: Livio Trentin, Andrea Visentin • S. Giovanni Battista Hospital, Turin, Italy: Lisa Bonello • Laiko Hospital, University of Athens, Athens, Greece: Panayiotis Panayiotidis, Maria Dimou, Maria Roumelioti • IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy: Gianluigi Reda • University Hospital NHS Trust, Southampton, UK: Francesco Forconi, Samantha Drennan • G. Papanicolaou Hospital, Thessaloniki, Greece: Niki Stavroyianni • University of Melbourne, Melbourne, Australia: Constantine Tam • Hematology Unit, University Hospital, Modena, Italy: Roberto Marasca, Rossana Maffei • Royal North Shore Hospital, University of Sydney, Sydney, Australia: Stephen Mulligan, Giles Best • Città della Salute e della Scienza, University of Turin, Turin, Italy: Marta Coscia, Candida Vitale, Valentina Griggio • University of Cambridge, Cambridge, UK: Ingo Ringshausen, Andrew Moore • Dubrava University Hospital, Zagreb, Croatia: Ozren Jaksic • Royal Bournemouth Hospital, Bournemouth, UK: Zadie Davis • Fundaleu, Buenos Aires, Argentina: Carolina Pavlovsky, Evelyn Casares • Service d'Hématologie Institut Universitaire Cancerologie Toulouse-Oncopole, Toulouse, France: Loïc Ysebaert, Anne Quillet-Mary • 1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary: Csaba Bödör; Richárd Kiss • Karolinska Institutet, Stockholm: Diego Cortese, Aron Skaftason • Institute of Applied Biosciences, CERTH, Thessaloniki: Kostas Stamatopoulos, Stavroula Ntoufa • ERIC Office: Esther López, Natalie Sorolla • Thanks to the support of

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