Chronic Lymhocytic Leukaemia: Treatment of the Elderly - European Medical Journal

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Chronic Lymhocytic Leukaemia: Treatment of the Elderly

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Hematology
Author:
*Barbara Eichhorst

German Chronic Lymphocytic Leukemia Study Group (GCLLSG), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
*Correspondence to [email protected]

Citation:
EMJ Hematol. ;4[1]:75-76. Abstract Review No. AR8.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

Chronic lymphocytic leukaemia (CLL) mainly affects elderly patients.1 With the increasing comorbidity burden and frailty in elderly patients, evaluation of functional status before treatment initiation is essential. So far, there is no ideal tool to measure the comorbidity burden, but geriatric assessment for example, with the G8 score2 before treatment initiation, is strongly recommended.3,4 While more intensive combination regimens based on chemotherapy plus antibody, such as the combination of fludarabine, cyclophosphamide, and rituximab (FCR), are standard in younger and/or physically fit patients, with concomitant diseases and physical fitness playing a major role in the selection of treatment for the elderly who do not tolerate such regimens well.5 Dose reductions or milder chemoimmunotherapy regimens are well tolerated in the elderly and yield promising results.6,7 The combination of chlorambucil plus a CD20 antibody has become the new standard first-line therapy in many countries because it yields long progression-free survival (PFS) rates of 15–27 months.8-10 Data from the CLL11 study presented at European Hematology Association (EHA) Congress 2016 showed that achieving a negative measure of minimal residual disease in peripheral blood or bone marrow by polymerase chain reaction was associated with significantly longer PFS among elder patients being treated with chlorambucil plus rituximab or obinutuzumab.11

With the approval of new oral drugs that inhibit kinases attached to the B cell receptor, better treatment options which are well tolerated are now available for relapsed CLL patients12,13 as well as front-line therapy.14 A randomised Phase III study in elderly CLL patients showed a clear superiority of the Bruton’s tyrosine kinase inhibitor ibrutinib over chlorambucil alone for PFS and overall survival.14 However, even in a front-line setting minimal residual disease negativity is rarely achieved with the new substances. With these continuously administered substances, drug interactions and compliance have to be considered, particularly in elderly patients. A retrospective analysis presented at EHA 2016 showed that a different side effect profile has to be considered with each new compound, as for example atrial fibrillation, which may occur in elderly patients receiving ibrutinib.15 Current studies are investigating the bcl2 inhibitor venetoclax in front-line therapy of elderly. The combination with obinutuzumab was shown to be safe in a run-in phase study.16 These as well as many other data presented at EHA 2016 regarding kinase inhibitors show that the selection of optimal treatment for elderly CLL patients remains challenging.

References
Howlader N NA et al. SEER Cancer Statistics Review, 1975-2011, National Cancer Institute, Bethesda, Maryland, USA. 2014. Available at: http://seer.cancer.gov/archive/csr/1975_2011/. Last accessed: 23 June 2016. Hamaker ME et al. Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: A systematic review. Lancet Oncol. 2012;13(10);e437-44. Goede V et al.; German CLL Study Group. Interactions between comorbidity and treatment of chronic lymphocytic leukemia: Results of the German CLL Study Group. Haematologica. 2014;99(6):1095-100. Hamaker ME et al. The relevance of a geriatric assessment for elderly patients with a haematological malignancy--a systematic review. Leuk Res. 2014;38(3):275-83. Shvidel L et al. Conventional dose fludarabine-based regimens are effective but have excessive toxicity in elderly patients with refractory chronic lymphocytic leukemia. Leuk Lymphoma. 2003;44(11):1947-50. Dartigeas C et al. Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose-dense rituximab in elderly patients with chronic lymphocytic leukemia. Leuk lymphoma. 2015;28:1-7. Michallet A-S et al. Rituximab in combination with bendamustine or chlorambucil for the treatment of chronic lymphocytic leukaemia: Primary results from the randomised phase IIIb MABLE study. Leuk Lymphoma. 2015;56(Suppl 1):149. Goede V et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Eng J Med. 2014;370(12):1101-10. Hillmen P 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(9980):1873-83. Goede V et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: Updated results of the CLL11 study. Leukemia. 2015;29(7):1602-4. Ritgen M et al. Quantitative mrd is prognostic for progression-free and overall survival in elderly patients receiving chlorambucil alone or with obinutuzumab/rituximab: A prospective analysis of the GCLLSG CLL11 study. Abstract S428. EHA Learning Center, 9-12 June 2016. Furman RR et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Eng J Med. 2014;370(11):997-1007. Byrd JC et al. Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood. 2015;125(16):2497-506. Burger JA et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-37. Thompson P et al. Atrial fibrillation in CLl patients treated with ibruitnib: An international retrospective study. Abstract P224. EHA Learning Center, 9-11 June 2016. Fischer K et al. Results of the Safety Run-in Phase of CLL14 (BO25323): A prospective, open-label, multicenter randomized Phase III trial to compare the efficacy and safety of obinutuzumab and venetoclax (GDC0199/ ABT199) with obinutuzumab and chlorambucil in patients with previously untreated CLL and coexisting medical conditions. Blood. 2015;126(23):496.

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