eUpdate – Chronic Lymphocytic Leukaemia Treatment Recommendations

eUpdate – Chronic Lymphocytic Leukaemia Treatment Recommendations 

Published: 21 September 2016. Authors:B. Eichhorst1, T. Robak2, E. Montserrat3, P. Ghia4, P. Hillmen5, M. Hallek6 & C. Buske7, on behalf of the ESMO Guidelines Committee

1Klinik I für Innere Medizin, Universität zu Köln, Köln, Germany; 2Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland; 3Institute of Hematology and Oncology, Department of Hematology, Hospital Clinic, University of Barcelona, Barcelona, Spain; 4Department of Onco-Hematology and Division of Molecular Oncology, Università Vita-Salute San Raffaele, Fondazione Centro San Raffaele, IRCCS Istituto Scientifico San Raffaele, Milan, Italy; 5Institute of Oncology, St James’s University Hospital, Leeds, UK; 6Department I Internal Medicine, Center for Integrated Oncology Köln-Bonn, Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Köln; 7Comprehensive Cancer Center Ulm, Institute of Experimental Cancer Research, University Hospital, Ulm, Germany 

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

Section

Treatment of advanced disease stage - Front-line treatment

Text update

The Btk inhibitor ibrutinib was superior to chlorambucil alone regarding PFS and overall survival in a phase III study including mostly elderly patients [1]. If access is available, ibrutinib can be considered as an alternative treatment option to chlorambucil-based chemoimmunotherapy. However, lack of long-term experience with front-line therapy with ibrutinib must be taken into consideration [I, C].

Patients with TP53 deletion/mutation have a poor prognosis even after FCR therapy [2]. 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. In the relapse setting, ibrutinib and idelalisib plus rituximab are treatment options.

Recommendation

  • Frontline therapy with ibrutinib can be considered as an alternative to chlorambucil-based chemoimmunotherapy, if access is available [I, C].
  • It is recommended that patients with TP53 deletion/mutation are treated with ibrutinib or idelalisib plus rituximab in frontline and relapse settings [V, A]. In front-line, idelalisib plus rituximab should only be considered if patients are not suitable for ibrutinib.

References

  1. Burger JA, Tedeschi A, Barr PM et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med 2015; 373: 2425-2437.
  2. 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.

Update 2

Section

Treatment of advanced disease stage - Treatment of CLL complications 

Text update

Infections are a common complication in CLL patients, therefore use of immunosuppressive agents, as for example corticosteroids, should be restricted to a possible minimum. The use of prophylactic systemic immunoglobulin does not have an impact on OS [1, 2], and is only recommended in patients with severe hypogammaglobulinaemia and repeated infections [I, A]. Antibiotic and antiviral prophylaxis should be used in patients with recurrent infections and/or very high risk of developing infections (for example, pneumocystis prophylaxis with cotrimoxazole during treatment with chemoimmunotherapies based on purine analogues or bendamustine or during treatment with idelalisib plus rituximab) [IV, B]. Pneumococcal vaccination as well as seasonal flu vaccination is recommended in early stage CLL [IV, B]. Cytomegaly virus surveillance is recommended during treatment with idelalisib plus rituximab.

Recommendations

  • The use of prophylactic systemic immunoglobulin is only recommended in patients with severe hypogammaglobulinaemia and repeated infections [I, A].
  • Antibiotic and antiviral prophylaxis should be used in patients with recurrent infections and/or very high risk of developing infections [IV, B].
  • Pneumococcal vaccination as well as seasonal flu vaccination is recommended in early stage CLL [IV, B].

References

  1. Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial. Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia. N Engl J Med 1988; 319: 902-907.
  2. Raanani P, Gafter-Gvili A, Paul M et al. Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis. Leuk Lymphoma 2009; 50: 764-772.

Algorithm for Frontline Treatment

New Chronic Lymphoblastic Leukamia Treatment