Diagnosis, treatment and supportive management of chronic lymphocytic leukemia: recommendations of the Dutch HOVON CLL working group

References

• van der Straten L, Levin M-D, Visser O, et al. Survival continues to increase in chronic lymphocytic leukaemia: a population-based analysis among 20 468 patients diagnosed in the Netherlands between 1989 and 2016. Br J Haematol. 2020;189(3):574–577.
   PubMed Web of Science ®Google Scholar
• Kristinsson SY, Dickman PW, Wilson WH, et al. Improved survival in chronic lymphocytic leukemia in the past decade: a population-based study including 11,179 patients diagnosed between 1973–2003 in Sweden. haematologica. 2009;94(9):1259–1265.
   PubMed Web of Science ®Google Scholar
• Thygesen LC, Nielsen OJ, Johansen C. Trends in adult leukemia incidence and survival in Denmark, 1943–2003. Cancer Causes Control. 2009;20(9):1671–1680.
   PubMed Web of Science ®Google Scholar
• Dores GM, Anderson WF, Curtis RE, et al. Chronic lymphocytic leukaemia and small lymphocytic lymphoma: overview of the descriptive epidemiology. Br J Haematol. 2007;139(5):809–819.
   PubMed Web of Science ®Google Scholar
• Smith A, Howell D, Patmore R, et al. Incidence of haematological malignancy by Sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer. 2011;105(11):1684–1692.
   PubMed Web of Science ®Google Scholar
• Kay NE, Hampel PJ, Van Dyke DL, et al. CLL update 2022: a continuing evolution in care. Blood Rev. 2022;54:100930.
   PubMed Web of Science ®Google Scholar
• van der Straten L, Maas CCHM, Levin M-D, et al. Long-term trends in the loss in expectation of life after a diagnosis of chronic lymphocytic leukemia: a population-based study in The Netherlands, 1989–2018. Blood Cancer J. 2022;12(4):72.
   PubMed Web of Science ®Google Scholar
• Shanafelt TD, Borah BJ, Finnes HD, et al. Impact of ibrutinib and idelalisib on the pharmaceutical cost of treating chronic lymphocytic leukemia at the individual and societal levels. J Oncol Pract. 2015;11(3):252–258.
   PubMed Web of Science ®Google Scholar
• Chen Q, Jain N, Ayer T, et al. Economic burden of chronic lymphocytic leukemia in the era of oral targeted therapies in the United States. J Clin Oncol. 2017;35(2):166–174.
   PubMed Web of Science ®Google Scholar
• Kersting S, Neppelenbroek SI, Visser HP, et al. Clinical practice guidelines for diagnosis and treatment of chronic lymphocytic leukemia (CLL) in The Netherlands. Clin Lymphoma Myeloma Leuk. 2018;18(1):52–57.
   PubMed Web of Science ®Google Scholar
• Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer. 2008.
   Google Scholar
• Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–2390.
   PubMed Web of Science ®Google Scholar
• Hallek M, Cheson BD, Catovsky D, et al. Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood. 2018;131(25):2745–2709. blood806398.
   PubMed Web of Science ®Google Scholar
• Rawstron A, Fazi C, Agathangelidis A, et al. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study. Leukemia. 2016;30(4):929–936.
   PubMed Web of Science ®Google Scholar
• Rawstron AC, Kreuzer KA, Soosapilla A, et al. Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: an European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project. Cytometry. 2018;94(1):121–128.
   PubMedGoogle Scholar
• Matutes E, Owusu-Ankomah K, Morilla R, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia. 1994;8(10):1640–1645.
   PubMed Web of Science ®Google Scholar
• Ginaldi L, De Martinis M, Matutes E, et al. Levels of expression of CD19 and CD20 in chronic B cell leukaemias. J Clin Pathol. 1998;51(5):364–369.
   PubMed Web of Science ®Google Scholar
• Moreau EJ, Matutes E, A'Hern RP, et al. Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b). Am J Clin Pathol. 1997;108(4):378–382.
   PubMed Web of Science ®Google Scholar
• Marti GE, Rawstron AC, Ghia P, et al. Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol. 2005;130(3):325–332.
   PubMed Web of Science ®Google Scholar
• Rai K, Sawitsky A, Cronkite E, et al. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46(2):219–234.
   PubMed Web of Science ®Google Scholar
• Binet J, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48(1):198–206.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–586.
   PubMed Web of Science ®Google Scholar
• Döhner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910–1916.
   PubMed Web of Science ®Google Scholar
• Zenz T, Eichhorst B, Busch R, et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28(29):4473–4479.
   PubMed Web of Science ®Google Scholar
• Rossi D, Cerri M, Deambrogi C, et al. The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness. Clin Cancer Res. 2009;15(3):995–1004.
   PubMed Web of Science ®Google Scholar
• Malcikova J, Tausch E, Rossi D, et al. ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia-update on methodological approaches and results interpretation. Leukemia. 2018;32(5):1070–1080.
   PubMed Web of Science ®Google Scholar
• Rossi D, Khiabanian H, Spina V, et al. Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. Blood. 2014;123(14):2139–2147.
   PubMed Web of Science ®Google Scholar
• Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94(6):1840–1847.
   PubMed Web of Science ®Google Scholar
• Hamblin TJ, Davis Z, Gardiner A, et al. Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94(6):1848–1854.
   PubMed Web of Science ®Google Scholar
• Del Giudice I, Mauro FR, De Propris MS, et al. White blood cell count at diagnosis and immunoglobulin variable region gene mutations are independent predictors of treatment-free survival in young patients with stage a chronic lymphocytic leukemia. Haematologica. 2011;96(4):626–630.
   PubMed Web of Science ®Google Scholar
• Agathangelidis A, Chatzidimitriou A, Gemenetzi K, et al. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood. 2021;137(10):1365–1376.
   PubMed Web of Science ®Google Scholar
• Jaramillo S, Agathangelidis A, Schneider C, et al. Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG). Haematologica. 2020;105(11):2598–2607.
   PubMed Web of Science ®Google Scholar
• Rosenquist R, Ghia P, Hadzidimitriou A, et al. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: updated ERIC recommendations. Leukemia. 2017;31(7):1477–1481.
   PubMed Web of Science ®Google Scholar
• Gordon MJ, Churnetski M, Alqahtani H, et al. Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib. Cancer. 2018;124(15):3192–3200.
   PubMed Web of Science ®Google Scholar
• Thompson PA, Tam CS, O’Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2016;127(3):303–309.
   PubMed Web of Science ®Google Scholar
• Tam CS, O'Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112(4):975–980.
   PubMed Web of Science ®Google Scholar
• Chai-Adisaksopha C, Brown JR. FCR achieves long-term durable remissions in patients with IGHV-mutated CLL. Blood. 2017;130(21):2278–2282.
   PubMed Web of Science ®Google Scholar
• Eichhorst B, Fink A-M, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016;17(7):928–942.
   PubMed Web of Science ®Google Scholar
• da Cunha-Bang C, Rostgaard K, Andersen MA, et al. Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population-based study. Br J Haematol. 2021;193(2):339–345.
   PubMed Web of Science ®Google Scholar
• Benjamini O, Jain P, Trinh L, et al. Second cancers in patients with Chronic Lymphocytic Leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes. Leuk Lymphoma. 2015;56(6):1643–1650.
   PubMed Web of Science ®Google Scholar
• Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101–1110.
   PubMed Web of Science ®Google Scholar
• Kater AP, Seymour JF, Hillmen P, et al. 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. 2019;37(4):269–277.
   PubMed Web of Science ®Google Scholar
• Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278–1291.
   PubMed Web of Science ®Google Scholar
• Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib–rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381(5):432–443.
   PubMed Web of Science ®Google Scholar
• Moreno C, Greil R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43–56.
   PubMed Web of Science ®Google Scholar
• Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379(26):2517–2528.
   PubMed Web of Science ®Google Scholar
• Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225–2236.
   PubMed Web of Science ®Google Scholar
• van Gelder M, Tournilhac O, Te Raa D, et al. Front-line chemo-immunotherapy is not inferior to ibrutinib in CLL. Ann Oncol. 2021;32(11):1442–1443.
   PubMed Web of Science ®Google Scholar
• Hillmen P, Pitchford A, Bloor A, et al. Ibrutinib plus rituximab is superior to FCR in previously untreated CLL: results of the phase III NCRI FLAIR trial. Blood. 2021;138(Supplement 1):642–642.
   Google Scholar
• Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127(2):208–215.
   PubMed Web of Science ®Google Scholar
• Lampson BL, Yu L, Glynn RJ, et al. Ventricular arrhythmias and sudden death in patients taking ibrutinib. Blood. 2017;129(18):2581–2584.
   PubMed Web of Science ®Google Scholar
• Ysebaert L, Aurran Schleinitz T, Dartigeas C, et al. Real‐world results of ibrutinib in relapsed/refractory CLL in France: Early results on a large series of 428 patients. Am J Hematol. 2017;92(8):E166–E168. ‐
   PubMed Web of Science ®Google Scholar
• Straten L, Levin M‐D, Visser O, et al. The effectiveness of ibrutinib in chronic lymphocytic leukaemia: a nationwide, population-based study in The Netherlands. Br J Haematol. 2020;188(6):e80–e112.
   PubMed Web of Science ®Google Scholar
• Mato AR, Nabhan C, Thompson MC, et al. Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis. Haematologica. 2018;103(5):874–879.
   PubMed Web of Science ®Google Scholar
• Forum UC. Ibrutinib for relapsed/refractory chronic lymphocytic leukemia: a UK and Ireland analysis of outcomes in 315 patients. haematologica. 2016;101(12):1563.
   PubMed Web of Science ®Google Scholar
• Mato AR, Roeker LE, Jacobs R, et al. Assessment of the efficacy of therapies following venetoclax discontinuation in CLL reveals BTK inhibition as an effective strategy. Clin Cancer Res. 2020;26(14):3589–3596.
   PubMed Web of Science ®Google Scholar
• Lin VS, Lew TE, Handunnetti SM, et al. BTK inhibitor therapy is effective in patients with CLL resistant to venetoclax. Blood. 2020;135(25):2266–2270.
   PubMed Web of Science ®Google Scholar
• Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164–1174.
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. Ibrutinib monotherapy versus fixed-duration venetoclax plus obinutuzumab versus fixed-duration ibrutinib plus venetoclax in patients with previously untreated chronic lymphocytic leukaemia (CLL) (CLL17) 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04608318
   Google Scholar
• Burger JA, Barr PM, Robak T, et al. 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. 2020;34(3):787–798.
   PubMed Web of Science ®Google Scholar
• Barr PM, Robak T, Owen C, et al. Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2. Haematologica. 2018;103(9):1502–1510.
   PubMed Web of Science ®Google Scholar
• Coutré SE, Barrientos JC, Brown JR, et al. Management of adverse events associated with idelalisib treatment: expert panel opinion. Leuk Lymphoma. 2015;56(10):2779–2786.
   PubMed Web of Science ®Google Scholar
• de Weerdt I, Koopmans SM, Kater AP, et al. Incidence and management of toxicity associated with ibrutinib and idelalisib: a practical approach. Haematologica. 2017;102(10):1629–1639.
   PubMed Web of Science ®Google Scholar
• Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annal Oncol. 2020;26:78–84.
   Google Scholar
• Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107–1120.
   PubMed Web of Science ®Google Scholar
• Byrd JC, Brown JR, O’Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213–223.
   PubMed Web of Science ®Google Scholar
• Ghia P, Pluta A, Wach M, et al. ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020:38:2849–2861.
   PubMed Web of Science ®Google Scholar
• Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42.
   PubMed Web of Science ®Google Scholar
• Farooqui MZ, Valdez J, Martyr S, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Lancet Oncol. 2015;16(2):169–176.
   PubMed Web of Science ®Google Scholar
• Mato A, Hill B, Lamanna N, et al. Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients. Ann Oncol. 2017;28(5):1050–1056.
   PubMed Web of Science ®Google Scholar
• Roeker LE, Dreger P, Brown JR, et al. Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents. Blood Adv. 2020;4(16):3977–3989.
   PubMed Web of Science ®Google Scholar
• Dreger P, Ghia P, Schetelig J, et al. High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies. Blood. 2018;132(9):892–902.
   PubMed Web of Science ®Google Scholar
• Gribben JG. How and when I do allogeneic transplant in CLL. Blood. 2018;132(1):31–39.
   PubMed Web of Science ®Google Scholar
• Stephens DM, Byrd JC. How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia. Blood. 2019;133(12):1298–1307.
   PubMed Web of Science ®Google Scholar
• Shanafelt TD, Wang V, Kay NE, et al. A randomized phase III study of ibrutinib (PCI-32765)-based therapy vs. standard fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy in untreated younger patients with chronic lymphocytic leukemia (CLL): a trial of the ECOG-ACRIN cancer research group (E1912). Am Soc Hematol. 2018.
   Web of Science ®Google Scholar
• Agency EM. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 30 August–2 September 2021 2021. Available from: https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-30-august-2-september-2021
   Google Scholar
• de Jong J, Hellemans P, De Wilde S, et al. A drug-drug interaction study of ibrutinib with moderate/strong CYP3A inhibitors in patients with B-cell malignancies. Leuk Lymphoma. 2018;59(12):2888–2895.
   PubMed Web of Science ®Google Scholar
• Mato AR, Timlin C, Ujjani C, et al. Comparable outcomes in chronic lymphocytic leukaemia (CLL) patients treated with reduced-dose ibrutinib: results from a multi-centre study. Br J Haematol. 2018;181(2):259–261.
   PubMed Web of Science ®Google Scholar
• Chen LS, Bose P, Cruz ND, et al. A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia. Blood. 2018;132(21):2249–2259.
   PubMed Web of Science ®Google Scholar
• Verboom DM, de JE, Klinkenberg R, et al. Atraumatische miltrupturen bij patienten met CLL kort na het staken van ibrutinib. Ned Tijdschr Hematol. 2021;18:374–378.
   Google Scholar
• Appels R, Betjes EMC, Bijl M, et al. Vaccinatie bij chronisch inflammatoire aandoeningen: handleiding. Available from: https://lci.rivm.nl/richtlijnen/vaccinatie-bij-chronisch-inflammatoire-aandoeningen
   Google Scholar
• Lucas M, Lee M, Lortan J, et al. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125(6):1354–1360.e4.
   PubMed Web of Science ®Google Scholar
• Scarfò L, Chatzikonstantinou T, Rigolin GM, et al. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus. Leukemia. 2020;34(9):2354–2363.
   PubMed Web of Science ®Google Scholar
• Mato AR, Roeker LE, Lamanna N, et al. Outcomes of COVID-19 in patients with CLL: a multicenter international experience. Blood. 2020;136(10):1134–1143.
   PubMed Web of Science ®Google Scholar
• Roeker LE, Eyre TA, Thompson MC, et al. COVID-19 in patients with CLL: improved survival outcomes and update on management strategies. Blood. 2021;138(18):1768–1773.
   PubMed Web of Science ®Google Scholar
• Martín‐Moro F, Marquet J, Piris M, et al. Survival study of hospitalised patients with concurrent COVID‐19 and haematological malignancies. Br J Haematol. 2020;190(1):e16–e20.
   PubMed Web of Science ®Google Scholar
• Kuderer NM, Choueiri TK, Shah DP, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020;395(10241):1907–1918.
   PubMed Web of Science ®Google Scholar
• Rossi D, Shadman M, Condoluci A, et al. How we manage patients with chronic lymphocytic leukemia during the SARS-CoV-2 pandemic. HemaSphere. 2020;4(4):e432.
   PubMed Web of Science ®Google Scholar
• RIVM. Risicogroepen en COVID-19 2022. Available from: https://www.rivm.nl/coronavirus-covid-19/risicogroepen.
   Google Scholar