Ibrutinib and Obinutuzumab in CLL: MRD Responses Sustained for Several Years with Deepest MRD Depletion in Patients with >1 Year Prior Ibrutinib Exposure

1year of IBR monotherapy; and 30 IBR-naïve R/R (median 1 prior treatment, range 1-3) started OBI 24 hours after first IBR dose. MRD assessment was performed according to ERIC guidelines with a maximum detection limit of 0.001%/10^-5.Results: IBR monotherapy in TN patients was well tolerated with 18/20 patients alive and 13/20 remaining on IBR after median 4.9 years follow-up (range 0-5.9). IBR was stopped due to toxicity (3), progression/relapse (2) or other causes (2). IBR-monotherapy resulted in median 0.65 log depletion per year in years 1-2, followed by relatively stable disease levels (median 0.2 log depletion per year) in the subsequent 3 years in 13/20 evaluable patients. Only 1 patient showed >0.3log increase in PB MRD level and this preceded clinical progression. No patients achieved an IWCLL CR/CRi and MRD was >0.01% in PB/BM in all patients at all time points.In the R/R group initially receiving IBR-monotherapy, 11/20 patients remain alive and 3/20 remain on IBR after a median 3.9 years follow-up (range 0.3-5.3). In this heavily pre-treated group, 10 did not enrol on the OBI Extension study (1 died, 1 progression/relapse, 4 ineligible/other causes, 4 patient preference) with 10/20 receiving OBI at median 16.2 months (range 13-19) after starting IBR-monotherapy of which 7/10 had resolved any lymphadenopathy pre-OBI. 2/10 achieved MRD-negative remission and stopped treatment, while 6/10 have since stopped IBR due to death (2), progression/relapse (3) or other causes (1). 30 R/R patients with no prior IBR exposure (most in first relapse) started IBR & OBI at the same time: 26/30 remain alive and 18/30 remain on IBR after median 3.0 years follow-up (range 0.8-4.2). IBR was stopped in 2/30 patients achieving MRD-negative remission while 10 stopped IBR due to death (2), disease progression/transformation (3), toxicity (4), or patient decision (1).There were no Grade 5 adverse events related to OBI. 3 months post-OBI, patients with >1 year prior IBR-monotherapy achieved a higher response rate (CR/CRi 50% vs. 30%), MRD response (0.3log increase at two sequential timepoints of which 4/7 have shown clinical disease progression and 3/7 still have low (1 year of IBR treatment and tumour bulk was low. One fifth of patients maintain