@article{Paula Cramer_Julia v. Tresckow_Sandra Robrecht_Jasmin Bahlo_Moritz Fürstenau_Petra Langerbeins_Natali Pflug_Othman Al-Sawaf_Werner J. Heinz_Ursula Vehling-Kaiser_Jan Dürig_Eugen Tausch_Manfred Hensel_Stephanie Sasse_Anna-Maria Fink_Kirsten Fischer_Karl-Anton Kreuzer_Sebastian Böttcher_Matthias Ritgen_Michael Kneba_Clemens-Martin Wendtner_Stephan Stilgenbauer_Barbara Eichhorst_Michael Hallek_2021, place={Pavia, Italy}, title={Bendamustine, followed by ofatumumab and ibrutinib in chronic lymphocytic leukemia (CLL2-BIO): primary endpoint analysis of a multicenter, open-label phase-II trial}, volume={106}, url={https://haematologica.org/article/view/9672}, DOI={10.3324/haematol.2019.223693}, abstractNote={<p>The introduction of targeted agents has revolutionized the treatment of chronic lymphocytic leukemia but only few patients achieve complete remissions and minimal residual disease negativity with ibrutinib monotherapy. This multicenter, investigator-initiated phase-II study evaluates a sequential treatment with two cycles of bendamustine debulking for patients with a higher tumor load, followed by ofatumumab and ibrutinib induction and maintenance treatment. An all-comer population, irrespective of prior treatment, physical fitness and genetic factors was included. The primary endpoint was the investigator assessed overall response rate at the end of induction treatment. Of 66 patients enrolled, one patient with early treatment discontinuation was excluded from the efficacy analysis as predefined by the protocol. Thirty-nine patients (60%) were treatment-naive and 26 patients (40%) had relapsed/refractory CLL, 21 patients (32%) had a del(17p) and/or TP53 mutation and 45 patients (69%) had an unmutated IGHV status. At the end of the induction, 60 of 65 patients (92%) responded and 9 (14%) achieved minimal residual disease negativity (&lt;10<sup>-4</sup>) in peripheral blood. No unexpected or cumulative toxicities occurred, most common CTC °III/IV adverse events were neutropenias, anaemia, infusion-related reactions, and diarrhoea. This sequential treatment of bendamustine debulking, followed by ofatumumab and ibrutinib was well tolerated without unexpected safety signals and showed a good efficacy with an overall response rate of 92%. Ongoing maintenance treatment aims at deeper responses with minimal residual disease negativity. However, ibrutinib should still be used as a single agent outside clinical trials. Clinicaltrials.gov number: <a class="external-ref external-ref-type-clintrialgov" href="/lookup/external-ref?link_type=CLINTRIALGOV&amp;access_num=NCT02689141&amp;atom=%2Fhaematol%2Fearly%2F2020%2F02%2F21%2Fhaematol.2019.223693.atom">NCT02689141</a>.</p&gt;}, number={2}, journal={Haematologica}, author={Paula Cramer and Julia v. Tresckow and Sandra Robrecht and Jasmin Bahlo and Moritz Fürstenau and Petra Langerbeins and Natali Pflug and Othman Al-Sawaf and Werner J. Heinz and Ursula Vehling-Kaiser and Jan Dürig and Eugen Tausch and Manfred Hensel and Stephanie Sasse and Anna-Maria Fink and Kirsten Fischer and Karl-Anton Kreuzer and Sebastian Böttcher and Matthias Ritgen and Michael Kneba and Clemens-Martin Wendtner and Stephan Stilgenbauer and Barbara Eichhorst and Michael Hallek}, year={2021}, month={Feb.}, pages={543-554} }