Available evidence for standard of care treatment strategies after BTKi discontinuation for CLL progression or intolerance
| Subsequent therapy . | Study design . | Number of patients in group of interest . | Clinical setting . | Prior therapies, median (range) . | ORR . | Progression data on subsequent therapy . | Survival data on subsequent therapy . |
|---|---|---|---|---|---|---|---|
| Venetoclax | Prospective24 | 91 | Progression on ibrutinib (n = 50), progression following ibrutinib discontinuation (n = 41) reasons for ibrutinib discontinuation: intolerance (n = 30), achievement of maximal benefit on ibrutinib (n = 6), completion of defined ibrutinib course (n = 3), unspecified (n = 2) | 4 (1-15) | 65% (63% in patients with prior ibrutinib intolerance, 54% for progression on ibrutinib) | 1-y PFS: 75% median PFS: 24.7 mo | 1-y OS: 91% |
| Retrospective26 | 13 | KI discontinuation (progression or intolerance) | Not reported | 76% | Not reported | Not reported | |
| Retrospective27 | Not reported | BCRi discontinuation (progression or intolerance) | Not reported | 74% | 24-mo PFS: 75% | Not reported | |
| Retrospective | 115 | Prior ibrutinib | 3 (0-11) | 69% | 12-mo PFS: 68% For entire cohort of 141 venetoclax treated patients, prior BTKi was not associated with inferior PFS | 12-mo OS: 88% For entire cohort of 141 venetoclax treated patients | |
| Retrospective43 | 62 post-BTKi alone, 10 post-BTKi and PI3Ki | BTKi discontinuation (progression or intolerance) | 3 (1-15) post BTKi alone, 5 (3-15) post BTKi and PI3Ki | 85% in post-BTKi alone, 80% in post BTKi and PI3Ki | 1-y PFS 65% Estimated for entire cohort, prior exposure to BTKi was not significantly associated with inferior PFS | 1-y OS 75% | |
| Median OS 61% Estimated for entire cohort, prior exposure to BTKi was not significantly associated with inferior OS | |||||||
| Acalabrutinib | Prospective23 | 33 | Ibrutinib intolerance | 4 (2-13) | 76% | 1-y PFS: 83% | Not reported |
| Idelalisib | Retrospective26 | 16 | Ibrutinib discontinuation (progression or intolerance) | Not reported | 28% | Not reported | Not reported |
| Retrospective27 | Not reported | Ibrutinib discontinuation (progression or intolerance) | Not reported | 46% | Median PFS: 9 mo | Not reported | |
| Umbralisib | Prospective38 | 44 | BTKi intolerant | 2 (1-7) | Not reported | Median PFS: 23.5 mo For entire cohort of 51 patients, including 7 with prior PI3Ki intolerance | Not reported |
| Subsequent therapy . | Study design . | Number of patients in group of interest . | Clinical setting . | Prior therapies, median (range) . | ORR . | Progression data on subsequent therapy . | Survival data on subsequent therapy . |
|---|---|---|---|---|---|---|---|
| Venetoclax | Prospective24 | 91 | Progression on ibrutinib (n = 50), progression following ibrutinib discontinuation (n = 41) reasons for ibrutinib discontinuation: intolerance (n = 30), achievement of maximal benefit on ibrutinib (n = 6), completion of defined ibrutinib course (n = 3), unspecified (n = 2) | 4 (1-15) | 65% (63% in patients with prior ibrutinib intolerance, 54% for progression on ibrutinib) | 1-y PFS: 75% median PFS: 24.7 mo | 1-y OS: 91% |
| Retrospective26 | 13 | KI discontinuation (progression or intolerance) | Not reported | 76% | Not reported | Not reported | |
| Retrospective27 | Not reported | BCRi discontinuation (progression or intolerance) | Not reported | 74% | 24-mo PFS: 75% | Not reported | |
| Retrospective | 115 | Prior ibrutinib | 3 (0-11) | 69% | 12-mo PFS: 68% For entire cohort of 141 venetoclax treated patients, prior BTKi was not associated with inferior PFS | 12-mo OS: 88% For entire cohort of 141 venetoclax treated patients | |
| Retrospective43 | 62 post-BTKi alone, 10 post-BTKi and PI3Ki | BTKi discontinuation (progression or intolerance) | 3 (1-15) post BTKi alone, 5 (3-15) post BTKi and PI3Ki | 85% in post-BTKi alone, 80% in post BTKi and PI3Ki | 1-y PFS 65% Estimated for entire cohort, prior exposure to BTKi was not significantly associated with inferior PFS | 1-y OS 75% | |
| Median OS 61% Estimated for entire cohort, prior exposure to BTKi was not significantly associated with inferior OS | |||||||
| Acalabrutinib | Prospective23 | 33 | Ibrutinib intolerance | 4 (2-13) | 76% | 1-y PFS: 83% | Not reported |
| Idelalisib | Retrospective26 | 16 | Ibrutinib discontinuation (progression or intolerance) | Not reported | 28% | Not reported | Not reported |
| Retrospective27 | Not reported | Ibrutinib discontinuation (progression or intolerance) | Not reported | 46% | Median PFS: 9 mo | Not reported | |
| Umbralisib | Prospective38 | 44 | BTKi intolerant | 2 (1-7) | Not reported | Median PFS: 23.5 mo For entire cohort of 51 patients, including 7 with prior PI3Ki intolerance | Not reported |