Table 3.
Available evidence for standard of care treatment strategies after venetoclax discontinuation for 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 or venetoclax/rituximab | Prospective9 | 14 | Progression after fixed-duration venetoclax/rituximab (13 completed MURANO regimen, 1 discontinued early) | Not reported | 55% (of evaluable patients) | Not reported | Not reported |
| Ibrutinib | Prospective41 | 8 | Progression after fixed-duration venetoclax/rituximab | 1 (1-4) | 100% | 4 on treatment, 3 with PD (median time on ibr 15 mo (3-48)) | No deaths reported |
| Retrospective44 | 27 | Venetoclax discontinuation (18 with PD, 9 for other reasons) | 2 (0-9) | 56% | 9 patients progressed on ibrutinib, time on ibrutinib 3-53 mo | Not reported | |
| Retrospective27 | 6 | Progression on venetoclax | 4 (1-7) | 5/6 with PR | 3 of 6 remain on therapy (6, 13, and 16 mo on therapy) | 3 deaths (2 of toxicity, 1 due to progression) | |
| BTKi | Retrospective28 | 44 | Venetoclax discontinuation (progression, toxicity), BTK naïve | 2 (0-8) | 84% | Median PFS 32 mo | Not reported |
| Retrospective28 | 30 | Venetoclax discontinuation (progression, toxicity), BTK exposed (33% intolerant, 66% resistant) | 4 (1-11) | 53% | Median PFS 12 mo | Not reported | |
| Retrospective42 | 23 | Venetoclax resistance, BTK naïve | 4 (2-9) | 91% | Median PFS 34 mo | ||
| PI3Ki | Retrospective28 | 17 | Venetoclax discontinuation (progression, toxicity), BTK exposed, PI3K naive | 4 (1-6) | 47% | Median PFS 5 mo | Not reported |