Individualisierte Therapie der chronischen lymphatischen Leukämie

Abstract

Because of the excellent prognosis in early asymptomatic stage of the disease all patients outside clinical trial should undergo “watch & wait” independently of their individual risk profile. Prognostic markers and scoring systems, as the CLL international prognostic index (CLL-IPI), help predicting the individual prognosis. In advanced stage disease standard frontline therapy in patients without high risk factors is still the combination of chemotherapy and CD20-antibody. However, particularly elderly patients with unfavorable prognostic factors may alternatively be treated with the Btk-inhibitor. Novel targeted agents are the treatment of choice in presence of high risk prognostic factors as well as in most relapsed situations. They are currently tested in currently ongoing trials in frontline.

Die Prognose der CLL ist ziemlich heterogen; dennoch erreichen viele Patienten ein sehr langes krankheitsfreies Überleben. Mittlerweile lässt sich der individuelle Krankheitsverlauf durch Prognosefaktoren besser einschätzen, vor allem durch nachgewiesene genetische Veränderungen der CLL-Zellen. Der Beitrag stellt bewährte sowie vielversprechende alternative Behandlungskonzepte vor, die sich durch die Zulassung neuer zielgerichteter Substanzen ergeben.

Schlüsselwörter

Chronische lymphatische Leukämie (CLL) - Chemo-Immuntherapie - zielgerichtete Substanzen

Key words

chronic lymphocytic leukemia (CLL) - chemoimmunotherapy - targeted drugs

• Literatur

• 1 Howlader N, Noone AM, Krapcho M. et al. SEER Cancer Statistics Review, 1975–2011, National Cancer Institute. Bethesda, MD. Im Internet: https://seer.cancer.gov/csr/1975_2011/ , based on November 2013 SEER data submission, posted to the SEER web site, April 2014
• 2 Swerdlow SH, Campo E, Pileri SA. et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127: 2375-2390
• 3 Hallek M, Cheson BD, Catovsky D. et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446-5456
• 4 Rai KR, Sawitsky A, Cronkite EP. et al. Clinical staging of chronic lymphocytic leukemia. Blood 1975; 46: 219-234
• 5 Binet JL, Auquier A, Dighiero G. et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 1981; 48: 198-206
• 6 International CLL-IPI-working-group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol 2016; 17: 779-790
• 7 Zenz T, Eichhorst B, Busch R. et al. TP53 Mutation and Survival in Chronic Lymphocytic Leukemia. J Clin Oncol 2010; 28: 4473-4479
• 8 AWMF (Federführende Fachgesellschaft DGHO). S3-Leitlinie: Diagnostik, Therapie und Nachsorge für Patienten mit einer chronischen lymphatischen Leukämie. Im Internet: www.awmf.org/leitlinien/detail/ll/018-032OL.html . Stand: 31.03.2018
• 9 Schweighofer CD, Cymbalista F, Müller C. et al. Early Versus Deferred Treatment With Combined Fludarabine, Cyclophosphamide and Rituximab (FCR) Improves Event-Free Survival In Patients With High-Risk Binet Stage A Chronic Lymphocytic Leukemia – First Results Of a Randomized German-French Cooperative Phase III Trial. Blood 2013; 122: 524
• 10 Fischer K, Bahlo J, Fink AM. et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood 2016; 127: 208-215
• 11 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 2010; 376: 1164-1174
• 12 Eichhorst B, Fink AM, Busch R. et al. Frontline chemoimmunotherapy with bendamustine and rituximab is inferior to fludarabine, cyclophosphamide and rituximab in physically fit patients with advanced chronic lymphocytic leukaemia: an international randomized phase III study (CLL10 study of the GCLLSG). Lancet Oncol 2016; 17 (07) 928-942
• 13 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
• 14 Goede V, Fischer K, Busch R. et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014; 370: 1101-1110
• 15 Goede V, Fischer K, Humphrey K. et al. Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R) plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): Final stage 1 results of the CLL11 (BO21004) phase III trial. J Clin Oncol 2013; 31: 7004
• 16 Hillmen P, Robak T, Janssens A. et al. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet 2015; 385: 1873-1883
• 17 von Tresckow J, Cramer P, Bahlo J. et al. CLL2-BIG – a Novel Treatment Regimen of Bendamustine Followed By GA101 and Ibrutinib Followed By Ibrutinib and GA101 Maintenance in Patients with Chronic Lymphocytic Leukemia (CLL): Interim Results of a Phase II-Trial. Blood 2015; 126: 4151
• 18 Furman RR, Sharman JP, Coutre SE. et al. Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med 2014; 370: 997-1007
• 19 Dreger P, Döhner H, Ritgen M. et al. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia:long-term clinical and MRD results of the GCLLSG CLL3X trial. Blood 2010; 116: 2438-2447
• 20 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