BTKis combined with venetoclax with or without anti-CD20 monoclonal antibodies in patients with R/R CLL
Trial phase . | Treatment . | No. of patients . | TP53 aberrations . | Schedule . | Strategy . | uMRD* rate . | Discontinuation rate . | Median follow-up . |
---|---|---|---|---|---|---|---|---|
Phase II48 | IBRU-VEN | 80 | 30% del(17p) and TP53 mutation | IBR for 3c, IBRU+ VEN 4-27c | MRD+ in BM could continue ibrutinib | 67% uMRD in BM at 24 c | 19% | 22 mo |
Phase II45 | IBRU-VEN | 53 | 22% del(17p) | IBRU 1-2c, IBRU+VEN after cycle 2 | PB/BM uMRD at cycle 8: cease therapy after cycle 14; PB/BM uMRD between cycles 14 and 26: cease therapy after cycle 26; MRD-positive at cycle 26: continue IBR monotherapy | uMRD 53% in PB at 12 mo; uMRD 36% in BM at 12 mo | Not reported | 21 mo |
Phase II49 | IBRU-VEN | 51 | 18% del(17p) and TP53 mutation | IBRU 1-2 c, IBR + VEN 3-15 c | > PR and BM uMRD after cycle 15 randomized to observation or IBR monotherapy*; MRD recrudescence retreated with combination | uMRD 55% in PB; uMRD 39% in BM | 16% | 15 mo |
Phase II50 | IBRU-VEN | 24 | 50% del(17p)/50% TP53 mutation | IBR+VEN for up to 2 y | uMRD CR on 2 assessments: discontinue all therapy or continue IBR monotherapy*; patients MRD-positive or less than CR: continue IBR monotherapy | 67% uMRD in BM at 12 mo (in 15 evaluable patients) | 12% | NA |
Phase Ib51 | IBRU-VEN-OBINU | 12 | 8% del(17p) | OBINU 1-8 c + IBRU 2-14 c + VEN 3-14 c | After cycle 14, can continue IBR monotherapy | 100% uMRD in PB/50% uMRD in BM at 14 c | Not reported | 24 mo |
Phase II52 | IBRU-VEN-OBINU | 25 | Not reported | OBINU 1-8 c + IBRU 2-14 c + VEN 3-14 c | After cycle 14, can continue IBR monotherapy | 100% uMRD in PB/50% uMRD in BM at 14 c | Not reported | 18 mo |
Trial phase . | Treatment . | No. of patients . | TP53 aberrations . | Schedule . | Strategy . | uMRD* rate . | Discontinuation rate . | Median follow-up . |
---|---|---|---|---|---|---|---|---|
Phase II48 | IBRU-VEN | 80 | 30% del(17p) and TP53 mutation | IBR for 3c, IBRU+ VEN 4-27c | MRD+ in BM could continue ibrutinib | 67% uMRD in BM at 24 c | 19% | 22 mo |
Phase II45 | IBRU-VEN | 53 | 22% del(17p) | IBRU 1-2c, IBRU+VEN after cycle 2 | PB/BM uMRD at cycle 8: cease therapy after cycle 14; PB/BM uMRD between cycles 14 and 26: cease therapy after cycle 26; MRD-positive at cycle 26: continue IBR monotherapy | uMRD 53% in PB at 12 mo; uMRD 36% in BM at 12 mo | Not reported | 21 mo |
Phase II49 | IBRU-VEN | 51 | 18% del(17p) and TP53 mutation | IBRU 1-2 c, IBR + VEN 3-15 c | > PR and BM uMRD after cycle 15 randomized to observation or IBR monotherapy*; MRD recrudescence retreated with combination | uMRD 55% in PB; uMRD 39% in BM | 16% | 15 mo |
Phase II50 | IBRU-VEN | 24 | 50% del(17p)/50% TP53 mutation | IBR+VEN for up to 2 y | uMRD CR on 2 assessments: discontinue all therapy or continue IBR monotherapy*; patients MRD-positive or less than CR: continue IBR monotherapy | 67% uMRD in BM at 12 mo (in 15 evaluable patients) | 12% | NA |
Phase Ib51 | IBRU-VEN-OBINU | 12 | 8% del(17p) | OBINU 1-8 c + IBRU 2-14 c + VEN 3-14 c | After cycle 14, can continue IBR monotherapy | 100% uMRD in PB/50% uMRD in BM at 14 c | Not reported | 24 mo |
Phase II52 | IBRU-VEN-OBINU | 25 | Not reported | OBINU 1-8 c + IBRU 2-14 c + VEN 3-14 c | After cycle 14, can continue IBR monotherapy | 100% uMRD in PB/50% uMRD in BM at 14 c | Not reported | 18 mo |
BM, bone marrow; c, cycles; IBR, ibrutinib; IBRU, ibrutinib; NA, not available; OBINU, obinutuzumab; PB, peripheral blood; PR, partial response; VEN, venetoclax.
uMRD defined as < 1 CLL cell per 10000 leukocytes.