How Have Targeted Agents Changed the Treatment Landscape for Elderly Patients with CLL?

Howlader N NA, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds. SEER Cancer Statistics Review, 1975–2016 National Cancer Institute. Bethesda, MD,2019 [Available from: https://seer.cancer.gov/csr/1975_2016/,.

Hallek M. Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment. Am J Hematol. 2019;94(11):1266–87. https://doi.org/10.1002/ajh.25595.

Article  PubMed  Google Scholar 

Pulte D, Redaniel MT, Bird J, et al. Survival for patients with chronic leukemias in the US and Britain: age-related disparities and changes in the early 21st century. Eur J Haematol. 2015;94(6):540–5. https://doi.org/10.1111/ejh.12468.

Article  PubMed  Google Scholar 

Puts MT, Santos B, Hardt J, et al. An update on a systematic review of the use of geriatric assessment for older adults in oncology. Ann Oncol. 2014;25(2):307–15. https://doi.org/10.1093/annonc/mdt386.

Article  PubMed  CAS  Google Scholar 

Ellis G, Whitehead MA, Robinson D, et al. Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials. BMJ. 2011;343: d6553. https://doi.org/10.1136/bmj.d6553.

Article  PubMed  PubMed Central  Google Scholar 

Hamaker ME, Prins MC, Stauder R. The relevance of a geriatric assessment for elderly patients with a haematological malignancy–a systematic review. Leuk Res. 2014;38(3):275–83. https://doi.org/10.1016/j.leukres.2013.12.018.

Article  PubMed  CAS  Google Scholar 

Hamaker ME, Mitrovic M, Stauder R. The G8 screening tool detects relevant geriatric impairments and predicts survival in elderly patients with a haematological malignancy. Ann Hematol. 2014;93(6):1031–40. https://doi.org/10.1007/s00277-013-2001-0.

Article  PubMed  CAS  Google Scholar 

Winkelmann N, Petersen I, Kiehntopf M, et al. Results of comprehensive geriatric assessment effect survival in patients with malignant lymphoma. J Cancer Res Clin Oncol. 2011;137(4):733–8. https://doi.org/10.1007/s00432-010-0933-5.

Article  PubMed  Google Scholar 

Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc. 1968;16(5):622–6. https://doi.org/10.1111/j.1532-5415.1968.tb02103.x.

Article  PubMed  CAS  Google Scholar 

Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83. https://doi.org/10.1016/0021-9681(87)90171-8.

Article  PubMed  CAS  Google Scholar 

Yancik R, Wesley MN, Ries LA, et al. Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study. Cancer 1998;82(11):2123–34. [published Online First: 1998/06/04]

Villavicencio A, Solans M, Zacarías-Pons L, et al. Comorbidities at diagnosis, survival, and cause of death in patients with chronic lymphocytic leukemia: a population-based study. Int J Environ Res Public Health. 2021;18(2). https://doi.org/10.3390/ijerph18020701

Strati P, Parikh SA, Chaffee KG, et al. Relationship between co-morbidities at diagnosis, survival and ultimate cause of death in patients with chronic lymphocytic leukaemia (CLL): a prospective cohort study. Br J Haematol. 2017;178(3):394–402. https://doi.org/10.1111/bjh.14785 (This study demonstrates that the cause of death for most patients with CLL is CLL-related.).

Article  PubMed  PubMed Central  CAS  Google Scholar 

Nabhan C, Aschebrook-Kilfoy B, Chiu BCH, et al. The impact of race, ethnicity, age and sex on clinical outcome in chronic lymphocytic leukemia: a comprehensive Surveillance, Epidemiology, and End Results analysis in the modern era. Leuk Lymphoma. 2014;55(12):2778–84. https://doi.org/10.3109/10428194.2014.898758.

Article  PubMed  Google Scholar 

Rotbain EC, Gordon MJ, Vainer N, et al. The CLL comorbidity index in a population-based cohort: a tool for clinical care and research. Blood Adv. 2022;6(8):2701–6. https://doi.org/10.1182/bloodadvances.2021005716 (This study validated the CLL comorbidity index in a large dataset.).

Article  PubMed  PubMed Central  Google Scholar 

Gordon MJ, Kaempf A, Sitlinger A, et al. The chronic lymphocytic leukemia comorbidity index (CLL-CI): a three-factor comorbidity model. Clin Cancer Res. 2021;27(17):4814–24. https://doi.org/10.1158/1078-0432.Ccr-20-3993 (This was the initial study which created the CLL Comorbitidy Index.).

Article  PubMed  PubMed Central  CAS  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 (London, England). 2010;376(9747):1164–74. https://doi.org/10.1016/s0140-6736(10)61381-5.

Article  CAS  Google Scholar 

Fischer K, Bahlo J, Fink A-M, et al. Extended follow up of the CLL8 protocol, a randomized phase-III trial of the German CLL Study Group (GCLLSG) comparing fludarabine and cyclophosphamide (FC) to FC plus rituximab (FCR) for previously untreated patients with chronic lymphocytic leukemia (CLL): results on survival, progression-free survival, delayed neutropenias and secondary malignancies confirm superiority of the FCR regimen. Blood. 2012;120(21):435–535.

Article  Google Scholar 

Keating MJ, O’Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(18):4079–88. https://doi.org/10.1200/jco.2005.12.051.

Article  CAS  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):303–9. https://doi.org/10.1182/blood-2015-09-667675.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Eichhorst B, Fink AM, 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):928–42. https://doi.org/10.1016/s1470-2045(16)30051-1.

Article  PubMed  CAS  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):1101–10. https://doi.org/10.1056/NEJMoa1313984.

Article  PubMed  CAS  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. https://doi.org/10.1056/NEJMoa1215637.

Article  PubMed  PubMed Central  CAS  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):213–23. https://doi.org/10.1056/NEJMoa1400376.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Munir T, Brown JR, O’Brien S, et al. 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. 2019;94(12):1353–63. https://doi.org/10.1002/ajh.25638.

Article  PubMed  PubMed Central  CAS  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):1502–10. https://doi.org/10.3324/haematol.2018.192328.

Article  PubMed  PubMed Central  CAS  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):2517–28. https://doi.org/10.1056/NEJMoa1812836 (This study demonstrated the improvement in progression free survival for elderly patients treated with ibrutinib containing regiments over bendamustine rituximab (chemoimmunotherapy)).

Article  PubMed  PubMed Central  CAS  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):787–98. https://doi.org/10.1038/s41375-019-0602-x.

Article  PubMed  CAS  Google Scholar 

Woyach JA, Ruppert AS, Heerema NA, et al. Long-term results of alliance A041202 show continued advantage of ibrutinib-based regimens compared with bendamustine plus rituximab (BR) chemoimmunotherapy. Blood. 2021;138(Supplement 1):639–739. https://doi.org/10.1182/blood-2021-153146.

Article  Google Scholar 

Burger JA, Cramer P, Barr PM, et al. Ibrutinib provides favourable survival outcomes in patients with comorbidities versus established therapies. Br J Haematol. 2019;186(1):175–80. https://doi.org/10.1111/bjh.15784.

Article  PubMed  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. https://doi.org/10.1016/S1470-2045(18)30788-5.

Article  PubMed  CAS  Google Scholar 

Center NCC. Chronic Lymphocytic Leukemia (Version 2.2022).

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 (London, England). 2020;395(10232):1278–91. https://doi.org/10.1016/s0140-6736(20)30262-2[publishedOnlineFirst:2020/04/20].

Article  CAS  Google Scholar 

Sharman JP, Egyed M, Jurczak W, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naïve chronic lymphocytic leukemia. Leukemia. 2022;36(4):1171–5. https://doi.org/10.1038/s41375-021-01485-x (This is the most recent update of the ELEVATE-TN trial demonstrating improvement in progression free surival for elderly patients or patients with comorbid medical conditions with CLL treated with acalabruitnib compared to chlorambcil-obinutuzumab.).

Article  PubMed  PubMed Central  CAS  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(25):2849–61. https://doi.org/10.1200/jco.19.03355.

Article  PubMed  CAS  Google Scholar 

Flinn IW, Hillmen P, Montillo M, et al. The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood. 2018;132(23):2446–55. https://doi.org/10.1182/blood-2018-05-850461.

Article  PubMed  PubMed Central  CAS 

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