. Dans-la-vignette-#3, Ibrutinib a été choisi 85 fois sur les 132 réponses (64.4%) et le R-Venetoclax 18 fois (13.6%). Les justifications associées à l'Ibrutinib étaient la logistique de prise en charge (68%), le profil de tolérance du patient (59%), la présentation clinique de la maladie (38%) et l'habitude de prescription (21%). Les justifications associées au R-Venetoclax

, Une ICT a été choisie dans 27 cas (20.5%) avec principalement R-Clb dans 10 cas et G

, Dans la vignette #4, l'Ibrutinib a été choisi 60 fois sur les 131 réponses (45.8%) et le R

, Les justifications associées à l'Ibrutinib étaient la cytogénétique / biologie moléculaire (73%), la présentation clinique de la maladie (40%), le profil de tolérance du patient (37%) et l'habitude de prescription (22%)

, Une ICT a été préférée dans 6 cas (4.6%) par R-Endoxan-Dexamethasone dans 5 cas

, Dans la vignette #5, l'Ibrutinib a été choisi 75 fois sur les 128 réponses (58.6%) et le R

, Les justifications associées à l'Ibrutinib étaient la cytogénétique / biologie moléculaire (88%), la présentation clinique de la maladie (39%), le profil de tolérance du patient (29%) et l'habitude de prescription (24%), Venetoclax 48 fois (37.5%)

, Une ICT a été choisie dans 1 cas (20.5%) et l'association R-Idelalisib a été choisie 4 fois

, 1%) (Figure 20 en annexe)

. Bibliographie,

. Spf, Estimations nationales de l'incidence et de la mortalité par cancer en France métropolitaine entre 1990 et 2018 -Hémopathies malignes : Étude à partir des registres des cancers du réseau Francim

A. Miranda-filho, Epidemiological patterns of leukaemia in 184 countries: a populationbased study, Lancet Haematol, vol.5, pp.14-24, 2018.

R. Weide, Survival improvement of patients with chronic lymphocytic leukemia (CLL) in routine care 1995-2017, Leukemia & Lymphoma, vol.61, pp.557-566, 2020.

D. Y. Yosifov, C. Wolf, S. Stilgenbauer, and D. Mertens, From Biology to Therapy: The CLL Success Story, HemaSphere, vol.3, p.175, 2019.

I. González-gascón-y-marín, Prognosis Assessment of Early-Stage Chronic Lymphocytic Leukemia: Are We Ready to Predict Clinical Evolution Without a Crystal Ball?, Clin Lymphoma Myeloma Leuk, 2020.

T. Nagasawa, Microenvironmental niches in the bone marrow required for B-cell development, Nat Rev Immunol, vol.6, pp.107-116, 2006.

M. Lefranc, IMGT, the international ImMunoGeneTics database, Nucleic Acids Research, vol.27, pp.209-212, 1999.
URL : https://hal.archives-ouvertes.fr/hal-02194546

T. A. Packard and J. C. Cambier, B lymphocyte antigen receptor signaling: initiation, amplification, and regulation, 1000.

W. N. Khan, Cell Receptor and BAFF Receptor Signaling Regulation of B Cell Homeostasis, The Journal of Immunology, vol.183, pp.3561-3567, 2009.

J. Chavez, E. Sahakian, and J. Pinilla-ibarz, Ibrutinib: An evidence-based review of its potential in the treatment of advanced chronic lymphocytic leukemia, Core evidence, vol.8, pp.37-45, 2013.

A. J. Mohamed, Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain, Immunological Reviews, vol.228, pp.58-73, 2009.

C. Thieblemont, Ibrutinib : applications cliniques et perspectives de développement dans les hémopathies malignes B, Bull Cancer, vol.102, pp.85-90, 2015.

Y. Tsujimoto, Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria?, Genes to Cells, vol.3, pp.697-707, 1998.

G. Fabbri and R. Dalla-favera, The molecular pathogenesis of chronic lymphocytic leukaemia

, Nat Rev Cancer, vol.16, pp.145-162, 2016.

Y. Kikushige, Self-Renewing Hematopoietic Stem Cell Is the Primary Target in Pathogenesis of Human Chronic Lymphocytic Leukemia, Cancer Cell, vol.20, pp.246-259, 2011.

M. Seifert, Cellular origin and pathophysiology of chronic lymphocytic leukemia, J. Exp

. Med, , vol.209, pp.2183-2198, 2012.

T. Zenz, D. Mertens, R. Küppers, H. Döhner, and S. Stilgenbauer, From pathogenesis to treatment of chronic lymphocytic leukaemia, Nat Rev Cancer, vol.10, pp.37-50, 2010.

A. Contri, Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis, J Clin Invest, vol.115, pp.369-378, 2005.

M. Buchner, Spleen Tyrosine Kinase Is Overexpressed and Represents a Potential Therapeutic Target in Chronic Lymphocytic Leukemia, Cancer Res, vol.69, pp.5424-5432, 2009.

Y. Liu, Y. Wang, J. Yang, Y. Bi, and H. Wang, ZAP-70 in chronic lymphocytic leukemia: A metaanalysis, Clin. Chim. Acta, vol.483, pp.82-88, 2018.

M. Crespo, ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia, N. Engl. J. Med, vol.348, pp.1764-1775, 2003.

C. Pepper, CD38 + chronic lymphocytic leukaemia cells co-express high levels of ZAP-70 and are functionally distinct from their CD38 ? counter-parts, Leukemia, vol.20, pp.743-744, 2006.

B. T. Messmer, In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells, J. Clin. Invest, vol.115, pp.755-764, 2005.

Y. Herishanu, The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia, Blood, vol.117, pp.563-574, 2011.

G. A. Calin, Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia, Proc. Natl. Acad. Sci. U.S.A, vol.99, pp.15524-15529, 2002.

F. Nguyen-khac, C. Borie, E. Callet-bauchu, V. Eclache, and S. Struski, Cytogenetics in the management of chronic lymphocytic leukemia: an update by the Groupe francophone de cytogénétique hématologique (GFCH), Annales de biologie clinique, vol.74, pp.561-567, 2016.

P. C. Nowell, The clonal evolution of tumor cell populations, Science, vol.194, pp.23-28, 1976.

D. A. Landau, Evolution and impact of subclonal mutations in chronic lymphocytic leukemia, Cell, vol.152, pp.714-726, 2013.

D. A. Landau, S. L. Carter, G. Getz, and C. J. Wu, Clonal evolution in hematological malignancies and therapeutic implications, Leukemia, vol.28, pp.34-43, 2014.

S. Stilgenbauer, Clonal evolution in chronic lymphocytic leukemia: acquisition of highrisk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival, Haematologica, vol.92, pp.1242-1245, 2007.

C. López, Clonal evolution in chronic lymphocytic leukemia: Analysis of correlations with IGHV mutational status, NOTCH1 mutations and clinical significance, Genes, Chromosomes and Cancer, vol.52, pp.920-927, 2013.

D. Koczkodaj, S. Popek-marciniec, S. Zmorzy?ski, E. W?sik-szczepanek, and A. A. Filip, Examination of clonal evolution in chronic lymphocytic leukemia, Med. Oncol, vol.36, p.79, 2019.

D. A. Landau, Mutations driving CLL and their evolution in progression and relapse, Nature, vol.526, pp.525-530, 2015.

F. Nadeu, Clinical impact of the subclonal architecture and mutational complexity in chronic lymphocytic leukemia, Leukemia, vol.32, pp.645-653, 2018.

D. Rossi, Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia, Blood, vol.123, pp.2139-2147, 2014.

J. Malcikova, Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia, Leukemia, vol.29, pp.877-885, 2015.

N. A. Amin, A Quantitative Analysis of Subclonal and Clonal Gene Mutations Pre-and Post-therapy in Chronic Lymphocytic Leukemia, Clin Cancer Res, vol.22, pp.4525-4535, 2016.

M. Hallek, Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial, The Lancet, vol.376, pp.1164-1174, 2010.

K. J. Maddocks, Etiology of Ibrutinib Discontinuation and Outcomes in Chronic Lymphocytic Leukemia Patients, JAMA Oncol, vol.1, pp.80-87, 2015.

P. Jain, Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib, Blood, vol.125, pp.2062-2067, 2015.

I. E. Ahn, Clonal evolution leading to ibrutinib resistance in chronic lymphocytic leukemia, Blood, vol.129, pp.1469-1479, 2017.

S. Kadri, Clonal evolution underlying leukemia progression and Richter transformation in patients with ibrutinib-relapsed CLL, Blood Adv, vol.1, pp.715-727, 2017.

R. R. Furman, Ibrutinib Resistance in Chronic Lymphocytic Leukemia, New England Journal of Medicine, vol.370, pp.2352-2354, 2014.

D. Mertens and S. Stilgenbauer, Ibrutinib-resistant CLL: unwanted and unwonted! Blood, vol.129, pp.1407-1409, 2017.

J. A. Burger, Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition, Nat Commun, vol.7, 2016.

D. Alpár, Dissection of Clonal Evolution By Temporal Mutation Profiling in Chronic Lymphocytic Leukemia Patients Treated with Ibrutinib, Blood, vol.130, pp.1457-1457, 2017.

E. Tausch, Venetoclax resistance and acquired BCL2 mutations in chronic lymphocytic leukemia, Haematologica, vol.104, pp.434-437, 2019.

J. Weiss, M. Peifer, C. D. Herling, L. P. Frenzel, and M. Hallek, Acquisition of the recurrent

, Gly101Val mutation in BCL2 confers resistance to venetoclax in patients with progressive chronic lymphocytic leukemia (Comment to Tausch et al.), Haematologica, vol.104, p.540, 2019.

P. Blombery, Acquisition of the Recurrent Gly101Val Mutation in BCL2 Confers Resistance to Venetoclax in Patients with Progressive Chronic Lymphocytic Leukemia, Cancer Discov, vol.9, pp.342-353, 2019.

C. D. Herling, Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia, Nat Commun, vol.9, 2018.

S. Thangavadivel and J. C. Byrd, Gly101Val BCL2 Mutation: One Step Closer to Understanding Venetoclax Resistance in CLL, Cancer Discov, vol.9, pp.320-322, 2019.

P. Blombery, Detection of Multiple Recurrent Novel BCL2 Mutations Co-Occurring with BCL2 Gly101Val in Patients with Chronic Lymphocytic Leukemia on Long Term Venetoclax, Blood, vol.134, pp.171-171, 2019.

B. J. Chyla, Identification of Recurrent Genomic Alterations in the Apoptotic Machinery in CLL Patients Treated with Venetoclax Monotherapy, Blood, vol.134, pp.172-172, 2019.

P. Blombery, Multiple BCL2 mutations cooccurring with Gly101Val emerge in chronic lymphocytic leukemia progression on venetoclax, Blood, vol.135, pp.773-777, 2020.

T. D. Shanafelt, Karyotype evolution on fluorescent in situ hybridization analysis is associated with short survival in patients with chronic lymphocytic leukemia and is related to CD49d expression, J. Clin. Oncol, vol.26, pp.5-6, 2008.

G. Itchaki and J. R. Brown, Experience with ibrutinib for first-line use in patients with chronic lymphocytic leukemia, Ther Adv Hematol, vol.9, pp.3-19, 2018.

P. Yeh, Circulating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia, Nat Commun, vol.8, 2017.

M. Else, R. Wade, D. Oscier, and D. Catovsky, The long-term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years, Br. J. Haematol, vol.172, pp.228-237, 2016.

D. Catovsky, Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial, Lancet, vol.370, pp.230-239, 2007.

I. W. Flinn, Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997, J. Clin. Oncol, vol.25, pp.793-798, 2007.

B. F. Eichhorst, Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia, Blood, vol.107, pp.885-891, 2006.

A. Michallet, Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study, Haematologica, vol.103, pp.698-706, 2018.

W. U. Knauf, Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia, J. Clin. Oncol, vol.27, pp.4378-4384, 2009.

G. Cartron, H. Watier, J. Golay, and P. Solal-celigny, From the bench to the bedside: ways to improve rituximab efficacy, Blood, vol.104, pp.2635-2642, 2004.

T. Cerny, B. Borisch, M. Introna, P. Johnson, and A. L. Rose, Mechanism of action of rituximab

, Anticancer Drugs, vol.13, issue.S3, p.10, 2002.

G. J. Weiner, Rituximab: mechanism of action, Semin Hematol, vol.47, pp.115-123, 2010.

S. M. Jaglowski, L. Alinari, R. Lapalombella, N. Muthusamy, and J. C. Byrd, The clinical application of monoclonal antibodies in chronic lymphocytic leukemia, Blood, vol.116, pp.3705-3714, 2010.

K. Fischer, Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial, Blood, vol.127, pp.208-215, 2016.

J. C. Byrd, Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011, Blood, vol.105, pp.49-53, 2005.

M. J. Keating, Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia, J. Clin. Oncol, vol.23, pp.4079-4088, 2005.

W. Wierda, Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia, J. Clin. Oncol, vol.23, pp.4070-4078, 2005.

H. Schulz, Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia, Blood, vol.100, pp.3115-3120, 2002.

T. Robak, Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia, J. Clin. Oncol, vol.28, pp.1756-1765, 2010.

F. Paul and G. Cartron, Infusion-related reactions to rituximab: frequency, mechanisms and predictors, Expert Rev Clin Immunol, vol.15, pp.383-389, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02626422

W. Yeo, Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab, J. Clin. Oncol, vol.27, pp.605-611, 2009.

S. Lanini, Risk of infection in patients with lymphoma receiving rituximab: systematic review and meta-analysis, BMC Med, vol.9, p.36, 2011.

J. C. Nissen, The risk of infections in hematologic patients treated with rituximab is not influenced by cumulative rituximab dosage -a single center experience, BMC Infectious Diseases, vol.14, p.364, 2014.

J. García-suárez, Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: impact of novel therapies, Am. J. Hematol, vol.80, pp.271-281, 2005.

S. L. Goldberg, Unusual viral infections (progressive multifocal leukoencephalopathy and cytomegalovirus disease) after high-dose chemotherapy with autologous blood stem cell rescue and peritransplantation rituximab, Blood, vol.99, pp.1486-1488, 2002.

A. Ivanov, Monoclonal antibodies directed to CD20 and HLA-DR can elicit homotypic adhesion followed by lysosome-mediated cell death in human lymphoma and leukemia cells, J. Clin. Invest, vol.119, pp.2143-2159, 2009.

E. Mössner, Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated Bcell cytotoxicity, Blood, vol.115, pp.4393-4402, 2010.

V. Goede, Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions, N. Engl. J. Med, vol.370, pp.1101-1110, 2014.

V. Kaur and A. Swami, Ibrutinib in CLL: a focus on adverse events, resistance, and novel approaches beyond ibrutinib, Ann. Hematol, vol.96, pp.1175-1184, 2017.

C. Thieblemont, Ibrutinib : applications cliniques et perspectives de développement dans les hémopathies malignes B. /data/revues/00074551/v102i6sS1/S0007455115312224, 2015.

J. A. Burger, Targeting the microenvironment in chronic lymphocytic leukemia is changing the therapeutic landscape, Curr Opin Oncol, vol.24, pp.643-649, 2012.

S. E. Herman, Ibrutinib Inhibits Both B-Cell Receptor and Toll-like Receptor Signaling in Chronic Lymphocytic Leukemia, Blood, vol.126, pp.313-313, 2015.

S. Ponader, The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo, Blood, vol.119, pp.1182-1189, 2012.

J. A. Dubovsky, Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes, Blood, vol.122, pp.2539-2549, 2013.

K. Kondo, Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B cell function and inhibition of the PD-1/PD-L1 pathway, Leukemia, vol.32, pp.960-970, 2018.

M. Levade, Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions, Blood, vol.124, pp.3991-3995, 2014.

J. R. Mcmullen, Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling, Blood, vol.124, pp.3829-3830, 2014.

T. Munir, Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma

, Am. J. Hematol, vol.94, pp.1353-1363, 2019.

J. C. Byrd, Ibrutinib Treatment for First-Line and Relapsed/Refractory Chronic Lymphocytic Leukemia: Final Analysis of the Pivotal Phase Ib/II PCYC-1102 Study, Clin Cancer Res, 2020.

J. A. Burger, Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study, Leukemia, vol.34, pp.787-798, 2020.

J. A. Woyach, Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL, N. Engl. J. Med, vol.379, pp.2517-2528, 2018.

T. D. Shanafelt, Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia, New England Journal of Medicine, vol.381, pp.432-443, 2019.

D. Ghez, Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib, Blood, vol.131, pp.1955-1959, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02341706

S. M. O'brien, Outcomes with ibrutinib by line of therapy and post-ibrutinib discontinuation in patients with chronic lymphocytic leukemia: Phase 3 analysis, Am. J. Hematol, vol.94, pp.554-562, 2019.

P. J. Hampel, Rapid disease progression following discontinuation of ibrutinib in patients with chronic lymphocytic leukemia treated in routine clinical practice, Leuk. Lymphoma, vol.60, pp.2712-2719, 2019.

S. A. Parikh, The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice, Cancer Med, vol.9, pp.3390-3399, 2020.

J. Golay, G. Ubiali, and M. Introna, The specific Bruton tyrosine kinase inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B cells with CD20 antibodies, Haematologica, vol.102, pp.400-403, 2017.

P. Ghia, Acalabrutinib vs Rituximab Plus Idelalisib (IdR) or Bendamustine (BR) by Investigator Choice in Relapsed/Refractory (RR) Chronic Lymphocytic Leukemia: Phase 3 ASCEND Study, vol.37, pp.86-87, 2019.

J. P. Sharman, Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial, Lancet, vol.395, pp.1278-1291, 2020.

C. Owen, N. L. Berinstein, A. Christofides, and L. H. Sehn, Review of Bruton tyrosine kinase inhibitors for the treatment of relapsed or refractory mantle cell lymphoma, Curr Oncol, vol.26, pp.233-240, 2019.

J. Hoellenriegel, The phosphoinositide 3?-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia, Blood, vol.118, pp.3603-3612, 2011.

B. J. Lannutti, CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability, Blood, vol.117, pp.591-594, 2011.

B. Vanhaesebroeck, J. Guillermet-guibert, M. Graupera, and B. Bilanges, The emerging mechanisms of isoform-specific PI3K signalling, Nature Reviews Molecular Cell Biology, vol.11, pp.329-341, 2010.

R. R. Furman, Idelalisib and rituximab in relapsed chronic lymphocytic leukemia, N. Engl. J. Med, vol.370, pp.997-1007, 2014.

S. E. Coutré, Management of adverse events associated with idelalisib treatment: expert panel opinion, Leuk Lymphoma, vol.56, pp.2779-2786, 2015.

A. J. Souers, ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets, Nat. Med, vol.19, pp.202-208, 2013.

V. Del-gaizo-moore, Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737, J Clin Invest, vol.117, pp.112-121, 2007.

M. A. Anderson, The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism, Blood, vol.127, pp.3215-3224, 2016.

M. Vogler, D. Dinsdale, M. J. Dyer, and G. M. Cohen, ABT-199 selectively inhibits BCL2 but not BCL2L1 and efficiently induces apoptosis of chronic lymphocytic leukaemic cells but not platelets, Br. J. Haematol, vol.163, pp.139-142, 2013.

M. Konopleva, Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia, Cancer Discov, vol.6, p.1106

J. F. Seymour, Four-Year Analysis of Murano Study Confirms Sustained Benefit of Time-Limited Venetoclax-Rituximab (VenR) in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL), Blood, vol.134, pp.355-355, 2019.

A. P. Kater, Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study, J. Clin. Oncol, vol.37, pp.269-277, 2019.

J. F. Seymour, Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia, N Engl J Med, vol.378, pp.1107-1120, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02348612

O. Al-sawaf, High efficacy of venetoclax plus obinutuzumab in patients with complex karyotype and chronic lymphocytic leukemia, Blood, vol.135, pp.866-870, 2020.

A. W. Roberts, Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia, N Engl J Med, vol.374, pp.311-322, 2016.

P. Strati, N. Jain, and S. O'brien, Chronic Lymphocytic Leukemia: Diagnosis and Treatment, Mayo Clin. Proc, vol.93, pp.651-664, 2018.

L. Iovino and M. Shadman, Novel Therapies in Chronic Lymphocytic Leukemia: A Rapidly Changing Landscape, Curr Treat Options Oncol, vol.21, p.24, 2020.

M. Hallek, Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment, American Journal of Hematology, vol.94, pp.1266-1287, 2019.

B. Eichhorst, Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Annals of Oncology, vol.26, pp.78-84, 2015.

C. Buske, ESMO Consensus Conference on malignant lymphoma: general perspectives and recommendations for the clinical management of the elderly patient with malignant lymphoma, Ann. Oncol, vol.29, pp.544-562, 2018.

C. Moreno, Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial, The Lancet Oncology, vol.20, pp.43-56, 2019.

M. A. Kharfan-dabaja, J. C. Chavez, K. A. Khorfan, and J. Pinilla-ibarz, Clinical and therapeutic implications of the mutational status of IgVH in patients with chronic lymphocytic leukemia, Cancer, vol.113, pp.897-906, 2008.

A. R. Mato, Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients, Ann. Oncol, vol.28, pp.1050-1056, 2017.

G. A. Fraser, Final 5-year findings from the phase 3 HELIOS study of ibrutinib plus bendamustine and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma, Leukemia & Lymphoma, vol.0, pp.1-10, 2020.

C. S. Tam, Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab), Blood, vol.124, pp.3059-3064, 2014.

R. Lentz, J. Feinglass, S. Ma, and N. Akhter, Risk factors for the development of atrial fibrillation on ibrutinib treatment, Leukemia & Lymphoma, vol.0, pp.1-7, 2019.

G. Reda, Predictors of atrial fibrillation in ibrutinib-treated CLL patients: a prospective study, J Hematol Oncol, vol.11, 2018.

T. E. Wiczer, Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib, vol.1, p.10, 2017.

J. Woyach, Resistance to Acalabrutinib in CLL Is Mediated Primarily By BTK Mutations, Blood, vol.134, pp.504-504, 2019.

J. A. Jones, Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial, The Lancet Oncology, vol.19, pp.65-75, 2018.

T. A. Eyre, Efficacy of venetoclax monotherapy in patients with relapsed chronic lymphocytic leukaemia in the post-BCR inhibitor setting: a UK wide analysis, 2019.

V. S. Lin, BTK inhibitor therapy is effective in patients with CLL resistant to venetoclax, Blood, 2020.

M. Fürstenau, M. Hallek, and B. Eichhorst, Sequential and combination treatments with novel agents in chronic lymphocytic leukemia, Haematologica, vol.104, pp.2144-2154, 2019.

M. L. Sorror, Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning, J. Clin. Oncol, vol.26, pp.4912-4920, 2008.

J. Schetelig, Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group, J. Clin. Oncol, vol.21, pp.2747-2753, 2003.

J. Gauthier, Allogeneic haematopoietic cell transplantation for indolent lymphomas: Guidelines from the Francophone Society Bone Marrow Transplantation and Cellular Therapy

, Bull Cancer, vol.104, pp.121-130, 2017.

J. W. Peabody, Measuring the Quality of Physician Practice by Using Clinical Vignettes: A Prospective Validation Study, Ann Intern Med, vol.141, p.771, 2004.

J. W. Peabody, J. Luck, P. Glassman, T. R. Dresselhaus, and M. Lee, Comparison of Vignettes, Standardized Patients, and Chart Abstraction: A Prospective Validation Study of 3 Methods for Measuring Quality, JAMA, vol.283, pp.1715-1722, 2000.

S. M. Camps, S. Chevret, and V. Lévy, How to use clinical vignettes in hematology-A pilot survey in the context of chronic lymphocytic leukemia, Leukemia Research, vol.33, pp.1328-1334, 2009.

C. G. Koedoot, Palliative chemotherapy or watchful waiting? A vignettes study among oncologists, J. Clin. Oncol, vol.20, pp.3658-3664, 2002.

M. A. Zarakas, J. V. Desai, G. Chamilos, and M. S. Lionakis, Fungal Infections with Ibrutinib and Other Small-Molecule Kinase Inhibitors, Curr Fungal Infect Rep, vol.13, pp.86-98, 2019.

T. Varughese, Serious Infections in Patients Receiving Ibrutinib for Treatment of Lymphoid Cancer, Clin. Infect. Dis, vol.67, pp.687-692, 2018.

U. S. , Highlights of Prescribing Information: Venclexta, 2018.

A. R. Mato, Real-world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States, Haematologica, vol.103, pp.1511-1517, 2018.

M. S. Davids, Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia, Clin Cancer Res, vol.24, pp.4371-4379, 2018.

T. A. Eyre, The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia, British Journal of Haematology, vol.188, pp.918-923, 2020.

A. Michallet, J. Rossignol, B. Cazin, and L. Ysebaert, Rituximab-cyclophosphamidedexamethasone combination in management of autoimmune cytopenias associated with chronic lymphocytic leukemia, Leuk. Lymphoma, vol.52, pp.1401-1403, 2011.

A. Quinquenel, Bendamustine and rituximab combination in the management of chronic lymphocytic leukemia-associated autoimmune hemolytic anemia: a multicentric retrospective study of the French CLL intergroup (GCFLLC/MW and GOELAMS), Am. J. Hematol, vol.90, pp.204-207, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01667670

A. Quinquenel, Ibrutinib and idelalisib in the management of CLL-associated autoimmune cytopenias: a study from the FILO group, American Journal of Hematology, vol.94, pp.183-185, 2019.

S. O'brien, Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study, The Lancet Oncology, vol.17, pp.1409-1418, 2016.

P. Hillmen, Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study, Journal of Clinical Oncology, 2019.

, A time-limited treatment with ibrutinib along with a reduced number of immunochemotherapy courses leads to profound and long-lasting responses in previously untreated cll patients

, European Hematology Association

J. Hoffmann, Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients, Front Immunol, vol.8, p.1956, 2017.

J. C. Riches, T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production, Blood, vol.121, pp.1612-1621, 2013.

R. Lemal and O. Tournilhac, State-of-the-art for CAR T-cell therapy for chronic lymphocytic leukemia in 2019, J Immunother Cancer, vol.7, p.202, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02299391

D. Mahadevan, Phase I study of samalizumab in chronic lymphocytic leukemia and multiple myeloma: blockade of the immune checkpoint CD200, Journal for ImmunoTherapy of Cancer, vol.7, p.227, 2019.

S. H. Gohil, Ibrutinib enhances the efficacy of ROR1 bispecific T cell engager mediated cytotoxicity in chronic lymphocytic leukaemia, Br. J. Haematol, vol.186, pp.380-382, 2019.