Results of secondary pathway inhibitors in relapsed/refractory CLL
| First PI (study) . | N (% 17p−) (% CK) . | Age, y (range) . | Cause of failure of first PI . | Second PI (n) . | ORR to second PI, % . | Outcome of second PI . | Median follow-up, mo (range) . | Reference . |
|---|---|---|---|---|---|---|---|---|
| Ibrutinib Idelalisib (US Real World) | 143 (37% 17p−) (33% CK) 35 (24% 17p−) (18% CK) | 60 (33-89) | Toxicity, 51% CLL, 29% Other, 20% | Idelalisib (22) Ibrutinib (16) Venetoclax (13) Untreated despite CLL progression/RT (10/59) | 28 64 76 | PFS 9 mo (If CLL was cause of first PI failure) PFS NR (if toxicity was cause of first PI failure) | 14 (0.3-51) (From first PI initiation) | 57 |
| Ibrutinib (M14-032) | 91 (47% 17p−) | 66 (28-81) | CLL, 100% | Venetoclax (91) | 65 (CR, 9) | PFS 25 mo | 14 | 47 |
| (IQR 8-18) | ||||||||
| (From second PI initiation) | ||||||||
| Idelalisib (M14-032) | 36 (22% 17p−) | 68 (56-85) | CLL, 100% | Venetoclax (36) | 67 (CR, 9) | 1-y PFS, 79% | 59 | |
| BCR inhibitor (M13-982) | 16 (100% 17p−) | NA | PD, 14; AE, 2 | Venetoclax (16) | 63 (CR, 13) | 2-y PFS, 50% | 16 (1-49)* | 48 |
| 2-y OS, 55% | ||||||||
| Venetoclax | 25 (40% 17p−) | 62 (47-78) | CLL, 32% RT, 68% | Ibrutinib (6) Ibrutinib (4, for CLL progression subsequent to RT treatment | 83 100 | OS after venetoclax failure CLL, 9 mo RT, 12 mo | NA | 50 |
| First PI (study) . | N (% 17p−) (% CK) . | Age, y (range) . | Cause of failure of first PI . | Second PI (n) . | ORR to second PI, % . | Outcome of second PI . | Median follow-up, mo (range) . | Reference . |
|---|---|---|---|---|---|---|---|---|
| Ibrutinib Idelalisib (US Real World) | 143 (37% 17p−) (33% CK) 35 (24% 17p−) (18% CK) | 60 (33-89) | Toxicity, 51% CLL, 29% Other, 20% | Idelalisib (22) Ibrutinib (16) Venetoclax (13) Untreated despite CLL progression/RT (10/59) | 28 64 76 | PFS 9 mo (If CLL was cause of first PI failure) PFS NR (if toxicity was cause of first PI failure) | 14 (0.3-51) (From first PI initiation) | 57 |
| Ibrutinib (M14-032) | 91 (47% 17p−) | 66 (28-81) | CLL, 100% | Venetoclax (91) | 65 (CR, 9) | PFS 25 mo | 14 | 47 |
| (IQR 8-18) | ||||||||
| (From second PI initiation) | ||||||||
| Idelalisib (M14-032) | 36 (22% 17p−) | 68 (56-85) | CLL, 100% | Venetoclax (36) | 67 (CR, 9) | 1-y PFS, 79% | 59 | |
| BCR inhibitor (M13-982) | 16 (100% 17p−) | NA | PD, 14; AE, 2 | Venetoclax (16) | 63 (CR, 13) | 2-y PFS, 50% | 16 (1-49)* | 48 |
| 2-y OS, 55% | ||||||||
| Venetoclax | 25 (40% 17p−) | 62 (47-78) | CLL, 32% RT, 68% | Ibrutinib (6) Ibrutinib (4, for CLL progression subsequent to RT treatment | 83 100 | OS after venetoclax failure CLL, 9 mo RT, 12 mo | NA | 50 |
Bold indicates PFS times.
IQR, interquartile range; NA, not available; NR, not reported; PD, progressive disease.
Time on venetoclax.