Page 20 - Haematologica-April 2018

Editorials
rituximab. In addition to the potential role of ibrutinib as a broad future first-line standard in CLL, we have to be aware that the BCL2 inhibitor, venetoclax, will further challenge any chemoimmunotherapy standard, both alone and in combination with antibodies, or even as a doublet including ibrutinib. The initial data regarding venetoclax in combination with the type II anti-CD20 mAb, obinutuzumab, seem to be very promising, with a MRD negativity rate of 100% in peripheral blood, based on a small run-in cohort as part of a large randomized phase III trial of the GCLLSG (CLL14 trial), which is cor- relating this combination with that of chlorambucil plus obinutuzumab (Table 1).8
Taken together, and in spite of some limitations in the trial design and trial performance, the data from MABLE are important as they represent the only available phase III data of the BR combination regimen compared to a chlorambucil/anti-CD20 comparator arm. The data from MABLE provide important cognizance with regard to the frontline treatment portfolio, keeping in mind that in many countries worldwide, upcoming treatment options based on B-cell receptor inhibitors, like ibrutinib, or BCL2 inhibitors such as venetoclax, will not be an available or affordable option in the near future.9 On account of the MABLE data, treating physicians will now have a ration- ale to use BR as an alternative treatment option compared to chlorambucil-based regimens in patients who are not eligible for more aggressive, fludarabine-based therapies. In other words, with respect to BR, and for the time being, there seems to be life in the old dog yet.
References
1. Michallet A-S, Aktan M, Hiddemann W, et al. Rituximab plus ben- damustine or chlorambucil for chronic lymphocytic leukemia: pri- mary analysis of the randomized, open-label MABLE study. Haematologica 2018;103(4):698-706.
2. Hillmen P, Robak T, Janssens A, et al. Chlorambucil plus ofatumum- ab 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- 1883.
3. 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.
4. Fischer K, Cramer P, Busch R, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lym- phocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2012;30(26):3209-3216.
5. Eichhorst B, Fink AM, Busch R, et al. Frontline chemoimmunothera- py with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) shows superior efficacy in comparison to bendamustine (B) and rituximab (BR) in previously untreated and physically fit patients (pts) with advanced chronic lymphocytic leukemia (CLL): final analysis of an international, randomized study of the German CLL Study Group (GCLLSG) (CLL10 Study). Blood. 2014;124(21):19.
6. Cheson BD, Brugger W, Damaj G, et al. Optimal use of bendamus- tine in hematologic disorders: Treatment recommendations from an international consensus panel - an update. Leuk Lymphoma. 2016;57(4):766-82.
7. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437.
8. Fischer K, Al-Sawaf O, Fink AM, et al. Venetoclax and obinutuzum- ab in chronic lymphocytic leukemia. Blood. 2017 May 11;129(19):2702-2705.
9. Chen Q, Jain N, Ayer T, et al. Economic burden of chronic lympho- cytic leukemia in the era of oral targeted therapies in the United States. J Clin Oncol. 2017;35(2):166-174.
564
haematologica | 2018; 103(4)