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P. Cramer et al.
treatment and three other patients had paresthesia or dysesthesia or sensory abnormalities during debulking treatment.
Discussion
This paper reports on a sequential combination treat- ment strategy, consisting of bendamustine debulking, fol- lowed by ofatumumab and ibrutinib in induction and a maintenance phase in a mixed population of treatment- naïve and relapsed/refractory patients. The primary end-
A
point of the trial was met: at the end of the induction treatment, an ORR of 92% and a MRD negativity rate of 14% in peripheral blood were achieved. As expected, response and MRD negativity rates were somewhat lower in patients with relapsed/refractory disease or with the high-risk markers del(17p)/TP53 mutation or unmutated IGHV. The response and MRD negativity rates achieved are inferior to those reported with standard chemoim- munotherapies,21-24 venetoclax either as a single agent or in combination with rituximab or obinutuzumab,25-27 and with ibrutinib plus obinutuzumab4,14 (Online Supplementary Appendix, Table S6, page 9). The efficacy results after 8
Figure 2. Improvement of response, time to first minimal residual disease negativity and treatment discontinuation. (A) Change in response with continued treatment. (B) Time to first documenta- tion of minimal residual disease negativity and treatment discontinua- tion. CR: complete remis- sion; CRi: CR with incom- plete recovery of bone marrow; PD: progressive disease; PR: partial response; SD: stable dis- ease; *Clinical CR/CRi is a remission fulfilling all criteria of a CR/CRi according to International Workshop on Chronic Lymphocytic Leukemia criteria except a bone marrow examination and/or computed tomog- raphy/magnetic reso- nance imaging scan: the lymphocyte count had to be normalized, patients had to be asymptomatic and have no evidence of lymphadenopathy and hepatosplenomegaly in clinical examination and ultrasound or other imag- ing.
B
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haematologica | 2021; 106(2)