Page 114 - Haematologica Vol. 107 - September 2022

ARTICLE - iLLUMINATE: final analysis C. Moreno et al.
Figure 4. Progression-free survival per investigator assessment according to TP53 aberration status (del[17p] or TP53 mutation) in the ibrutinib plus obinutuzumab arm. CI: confidence interval; mo: months; NE, not estimable; PFS, progression-free survival.
rates of 77% and 74% in patients wih and without del(17p)/TP53 mutation, respectively.
Time to next treatment
Over a median follow-up of 45 months, fewer patients re- ceiving ibrutinib plus obinutuzumab initiated subsequent treatment for CLL/SLL compared with those receiving chlorambucil plus obinutuzumab (3/113 [3%] vs. 55/116 [47%] patients, respectively). The median time to next treatment was not reached in the ibrutinib plus obinutu- zumab arm compared with 33 months (95% CI: 24 months-NE) in the chlorambucil plus obinutuzumab arm, corresponding to a 96% reduction in the risk of needing next-line therapy (HR=0.04; 95% CI: 0.01-0.13; P<0.0001).
Response rates
Consistent with the primary analysis, the ORR by investi- gator assessment was higher in the ibrutinib plus obinu- tuzumab arm (n=103/113; 91%) than in the chlorambucil plus obinutuzumab arm (n=94/116; 81%) (Figure 5). CR rates, including CRi, in the ibrutinib plus obinutuzumab arm (47 [42%]) were slightly increased relative to rates re- ported at the primary analysis (46 [41%]); CR/CRi rates in the chlorambucil plus obinutuzumab arm were unchanged compared to those reported at the primary analysis (n=20 [17%]; P<0.0001 for the difference between arms). The median duration of response was not reached in the ibrutinib plus obinutuzumab arm (95% CI: NE-NE) and was 19 months (95% CI: 16-31) in the chlorambucil plus obinu- tuzumab arm.
Minimal residual disease
Initially MRD information was obtained from BM from all patients at cycle 9 and upon achieving CR, but subsequent protocol amendments enabled data collection from both BM and PB, and from all responders on a scheduled basis thereafter. Overall, MRD assessments were obtained from 101/113 patients on ibrutinib plus obinutuzumab (93 BM and 90 PB) and from 92/116 patients in the chlorambucil plus obinutuzumab arm (84 BM and 60 PB). Most patients with undetectable MRD (<0.01%) were subsequently followed with at least one repeat MRD assessment (91% for ibrutinib plus obinutuzumab; 86% for chlorambucil plus obinutuzu- mab), with a median follow-up of 23 and 30 months, re- spectively, following initial attainment of undetectable MRD. Overall, 38% (43/113) of patients in the ibrutinib plus obi- nutuzumab arm achieved undetectable MRD in BM or PB compared with 25% (29/116) in the chlorambucil plus obi- nutuzumab arm (P=0.033) (Online Supplementary Table S2). Rates of undetectable MRD for the ibrutinib plus obi- nutuzumab arm were 25% for BM (28/113) and 33% for PB (37/113); rates for the chlorambucil plus obinutuzumab arm were 17% (20/116) in BM and 20% (23/116) in PB. In these patients, the cumulative rate of undetectable MRD (<0.01%) increased over the first 3 years with continuous ibrutinib therapy and then remained stable through final analysis (Figure 6). As expected, given the differences in PFS for the two arms following initial attainment of unde- tectable MRD, 60% of patients receiving ibrutinib plus obi- nutuzumab maintained undetectable MRD status through last PB or BM testing compared to 31% of patients receiv-
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