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eUpdate – Chronic Lymphocytic Leukaemia Treatment Recommendations

eUpdate – Chronic Lymphocytic Leukaemia Treatment Recommendations 

Published: 27 June 2017. Authors: ESMO Guidelines Committee

Clinical Practice Guidelines

This update refers to the Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Eichhorst B, Robak T, Montserrat P et al. Ann Oncol 2015; 26 (Suppl 5): v78-v84.

Update 1


Treatment of advanced disease stage - Front-line treatment

Text update

Patients with TP53 deletion/mutation have a poor prognosis even after FCR therapy [1]. Therefore, it is recommended that patients with TP53 deletion/mutation are treated with ibrutinib in front-line [V, A]. Because of severe infectious complications, the PI3K inhibitor idelalisib combined with rituximab is only recommended for frontline therapy in patients not suitable for Btk inhibitors, if anti-infective prophylaxis is taken and measures to prevent infection are followed. Patients unsuitable for BCR inhibitor therapy may otherwise be treated with the BCL2 inhibitor venetoclax [2].


  • Patients with del(17p) or TP53 mutation who are unsuitable for BCR inhibitor therapy may be treated with the BCL2 inhibitor venetoclax. 


  1. Hallek M, Fischer K, Fingerle-Rowson G et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia: a randomised, open-label, phase III trial. Lancet 2010;  376: 1164-1174.
  2. Roberts AW, Davids MS, Pagel JM et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med 2016; 374: 311-322.

Update 2


Treatment of advanced disease stage – Treatment of relapsed and refractory disease

Text update

If relapse occurs within 24-36 months after chemoimmunotherapy, or if the disease does not respond to any first-line therapy, the therapeutic regimen should be changed.

Treatment options include [III, B]:

  • Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib
  • PI3K inhibitor idelalisib in combination with rituximab
  • BCL2 antagonist venetoclax (if patient failed to BCR inhibitor therapy) [1]

Other chemoimmunotherapy combinations should only be administered if TP53 deletion/mutation was excluded (Figure 2).

Patients failing upon therapy with BCR inhibitors should preferentially be switched to a BCL2 antagonist when available. The second choice is a switch to another BCR inhibitor (e.g. from Btk inhibitor to PI3K inhibitor or vice versa). Fit patients achieving second remission following the second application of an inhibitor should proceed to allogeneic HSCT [V, B]. 


  • Patients failing upon BCR inhibitor therapy should be treated with a BCL2 inhibitor. 


  1. Stilgenbauer S, Eichhorst B, Schetelig J et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol 2016; 17: 768-778.

Algorithm for Front-line Treatment

New Chronic Lymphoblastic Leukamia Treatment

Treatment Options for Relapsed/Refractory CLL

New Chronic Lymphoblastic Leukamia Treatment relapsed/refractory

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