Pooled analysis of first-line treatment with targeted agents in patients with chronic lymphocytic leukemia aged 80 years and older

Abstract Patients aged 80 years and older make up a fifth of patients with CLL but are underrepresented in clinical trials. We analyzed the outcomes of these patients treated with targeted agents in the front-line setting in six trials of the German CLL Study Group. Targeted agents included venetoclax, ibrutinib, and idelalisib, mainly used in combination with anti-CD20 antibodies. Among 716 patients, 33 matched the selection criteria (5%). Of those, the majority had relevant comorbidity, organ dysfunctions, and/or high-/very high-risk disease. The overall response rate was 73%. The median progression-free survival was 49.2 months compared with those not reached in younger patients. There were 11 documented deaths of which two were deemed related to therapy. Additional results including 40 patients treated with BTK-inhibitors from the GCLLSG registry suggest that treatment with targeted agents is feasible and effective. Dedicated studies are warranted for this particular subgroup of patients.

[1]  A. Frustaci,et al.  P659: IBRUTINIB IN OVER-EIGHTIES PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: A MULTICENTER ITALIAN COHORT , 2022, HemaSphere.

[2]  H. Döhner,et al.  Phase 2 study of obinutuzumab (GA-101), ibrutinib and venetoclax (CLL2-GIVe) in patients with untreated high-risk chronic lymphocytic leukemia. , 2021, Blood.

[3]  L. Laurenti,et al.  Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review , 2021, Journal of clinical medicine.

[4]  M. Hallek,et al.  Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures , 2021, American journal of hematology.

[5]  V. Goede,et al.  Frailty assessment in the care of older people with haematological malignancies. , 2021, The Lancet. Healthy longevity.

[6]  V. Rossi,et al.  Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib? , 2021, Blood advances.

[7]  K. Rostgaard,et al.  Mapping comorbidity in chronic lymphocytic leukemia: impact of individual comorbidities on treatment, mortality, and causes of death , 2021, Leukemia.

[8]  M. Hallek,et al.  Bendamustine Followed By Obinutuzumab and Idelalisib in Patients with Chronic Lymphocytic Leukemia (CLL): CLL2-BCG Trial of the German CLL Study Group (GCLLSG) , 2020 .

[9]  M. Hallek,et al.  Bendamustine followed by ofatumumab and ibrutinib in chronic lymphocytic leukemia: primary endpoint analysis of a multicenter, open-label, phase II trial (CLL2-BIO) , 2020, Haematologica.

[10]  B. Cheson,et al.  The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia , 2020, British journal of haematology.

[11]  J. Byrd,et al.  ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic Leukemia (CLL). , 2019, Blood.

[12]  G. Abel,et al.  Gait speed, grip strength and clinical outcomes in older patients with hematologic malignancies. , 2019, Blood.

[13]  T. Kipps,et al.  Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. , 2019, The New England journal of medicine.

[14]  J. Byrd,et al.  Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab. , 2019, Blood.

[15]  M. Hallek,et al.  Bendamustine, Followed by Ofatumumab and Ibrutinib in Chronic Lymphocytic Leukaemia (CLL2-BIO): Primary Endpoint Analysis of a Multicentre, Open-Label Phase-II Trial , 2019, SSRN Electronic Journal.

[16]  R. Greil,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. , 2019, The Lancet. Oncology.

[17]  M. Hallek,et al.  CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia , 2018, Leukemia.

[18]  M. Hallek,et al.  Management of unfit elderly patients with chronic lymphocytic leukemia. , 2018, European journal of internal medicine.

[19]  Scott E. Smith,et al.  Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL , 2018, The New England journal of medicine.

[20]  M. Hallek,et al.  Outcome of patients aged 80 years or older treated for chronic lymphocytic leukaemia , 2018, British journal of haematology.

[21]  M. Hallek,et al.  Bendamustine followed by obinutuzumab and venetoclax in chronic lymphocytic leukaemia (CLL2-BAG): primary endpoint analysis of a multicentre, open-label, phase 2 trial. , 2018, The Lancet. Oncology.

[22]  S. James,et al.  Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib , 2018, Cancer.

[23]  Marco Montillo,et al.  Venetoclax–Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia , 2018, The New England journal of medicine.

[24]  M. Yassuda,et al.  Screening for Frailty With the FRAIL Scale: A Comparison With the Phenotype Criteria. , 2017, Journal of the American Medical Directors Association.

[25]  P. Feugier,et al.  Ibrutinib in very elderly patients with relapsed/refractory chronic lymphocytic leukemia: A real‐world experience of 71 patients treated in France: A study from the French Innovative Leukemia Organization (FILO) group , 2017, American journal of hematology.

[26]  T. Shanafelt,et al.  Management of chronic lymphocytic leukemia (CLL) in the elderly: a position paper from an international Society of Geriatric Oncology (SIOG) Task Force , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  M. Hallek,et al.  Evaluation of geriatric assessment in patients with chronic lymphocytic leukemia: Results of the CLL9 trial of the German CLL study group , 2016, Leukemia & lymphoma.

[28]  An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. , 2016, The Lancet. Oncology.

[29]  T. Kipps,et al.  Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. , 2015, The New England journal of medicine.

[30]  H. Wildiers,et al.  International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  H. Döhner,et al.  Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials , 2014, Haematologica.

[32]  ONSTANZE,et al.  GENOMIC ABERRATIONS AND SURVIVAL IN CHRONIC LYMPHOCYTIC LEUKEMIA , 2010 .

[33]  G. Jenkins,et al.  Comorbid conditions and survival in unselected, newly diagnosed patients with chronic lymphocytic leukemia , 2008, Leukemia & lymphoma.

[34]  A Benner,et al.  Genomic aberrations and survival in chronic lymphocytic leukemia. , 2000, The New England journal of medicine.