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. 2021 Dec 28;5(24):5490-5500.
doi: 10.1182/bloodadvances.2021004824.

Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib?

Alessandra Tedeschi  1 , Anna Maria Frustaci  1 , Francesca Romana Mauro  2 , Annalisa Chiarenza  3 , Marta Coscia  4 , Stefania Ciolli  5 , Gianluigi Reda  6 , Luca Laurenti  7 , Marzia Varettoni  8 , Roberta Murru  9 , Claudia Baratè  10 , Paolo Sportoletti  11 , Antonino Greco  12 , Chiara Borella  13 , Valentina Rossi  14 , Marina Deodato  1 , Annalisa Biagi  15 , Giulia Zamprogna  1 , Angelo Curto Pelle  3 , Gianfranco Lapietra  2 , Candida Vitale  4 , Francesca Morelli  5 , Ramona Cassin  6 , Alberto Fresa  7 , Chiara Cavalloni  8 , Massimiliano Postorino  15 , Claudia Ielo  2 , Roberto Cairoli  1 , Francesco Di Raimondo  3 , Marco Montillo  1 , Giovanni Del Poeta  15
Affiliations

Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib?

Alessandra Tedeschi et al. Blood Adv. .

Abstract

Functional reserve of organs and systems is known to be relevant in predicting immunochemotherapy tolerance. Age and comorbidities, assessed by the cumulative illness rating scale (CIRS), have been used to address chemotherapy intensity. In the ibrutinib era, it is still unclear whether age, CIRS, and Eastern Cooperative Oncology Group performance status (ECOG-PS) retain their predictive role on treatment vulnerability. In this series of 712 patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib outside clinical trials, baseline ECOG-PS and neutropenia resulted as the most accurate predictors of treatment feasibility and outcomes. Age did not independently influence survival and ibrutinib tolerance, indicating that not age per se, but age-related conditions, may affect drug management. We confirmed the role of CIRS > 6 as a predictor of a poorer progression- and event-free survival (PFS, EFS). The presence of a severe comorbidity was significantly associated with permanent dose reductions (PDRs), not translating into worse outcomes. As expected, del(17p) and/or TP53mut and previous therapies affected PFS, EFS, and overall survival. No study so far has analyzed the influence of concomitant medications and CYP3A inhibitors with ibrutinib. In our series, these factors had no impact, although CYP3A4 inhibitors use correlated with Cox regression analysis, with an increased risk of PDR. Despite the limitation of its retrospective nature, this large study confirmed the role of ECOG-PS as the most accurate predictor of ibrutinib feasibility and outcomes, and importantly, neutropenia emerged as a relevant tool influencing patients' vulnerability. Although CIRS > 6 retained a significant impact on PFS and EFS, its value should be confirmed by prospective studies.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
OS of the 712 patients according to tox-DTD. Overall survival of patients stratified according to the occurrence of discontinuation due to toxicity.
Figure 2.
Figure 2.
Outcomes in terms of PFS, EFS, and OS according to ECOG-PS. Impact of ECOG-PS on PFS (A), EFS (B), and OS (C).
Figure 3.
Figure 3.
PFS and EFS stratified by CIRS and age. PFS (A) and EFS (B) of the whole population according to CIRS score; PFS (C) and EFS (D) in patients <65 years according to CIRS score; PFS (E) and EFS (E) in patients ≥65 years according to CIRS score.
Figure 4.
Figure 4.
PFS and EFS stratified by CIRS3+ and age. PFS (A) and EFS (B) of the whole population according to CIRS3+; PFS (C) and EFS (D) in patients <65 years according to CIRS3+; PFS (E) and EFS (F) in patients ≥65 years according to CIRS3+.
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References

    1. SEER. Available at: http://seer.cancer.gov/. Accessed 25 May 2020.
    1. Stauder R, Eichhorst B, Hamaker ME, et al. . Management of chronic lymphocytic leukemia (CLL) in the elderly: a position paper from an international Society of Geriatric Oncology (SIOG) Task Force. Ann Oncol. 2017;28(2):218-227. - PubMed
    1. Eichhorst B, Hallek M, Goede V. Management of unfit elderly patients with chronic lymphocytic leukemia. Eur J Intern Med. 2018;58:7-13. - PubMed
    1. Eichhorst B, Fink AM, Bahlo J, et al. ; German CLL Study Group (GCLLSG) . 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
    1. 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

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