Results of approved pathway inhibitors in R/R CLL with TP53 abnormalities and/or complex karyotype
| Agent (study) . | Study type . | Aberration . | n . | Age in years (range) . | ORR (CR)* . | DOR (2 y) (median in mo) . | PFS (2 y) (median in mo) . | OS (2 y) (median in mo) . | Median follow-up, mo (range) . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|
| Ibrutinib (PCYC-1102/1103) | Prospective | 17p− | 34 | 79% (6%) | 31 mo | 57% (26) | 64% (57) | 47 (1-67) | 10 | |
| CK | 37 | 90% (7%) | 39 mo | 65% (33) | 75% (57) | 55 (1-67) | ||||
| Ibrutinib + rituximab | Prospective | 17p− | 21 | 86% (24%) | NA | 55% (32) | 73% (NR) | 47 (36-51)† | 7 | |
| CK | 15 | NA | NA | 55% (32) | 77% (NR) | |||||
| Ibrutinib (NCT01500733) | Prospective | 17p− | 16 | 62 (33-82)† | NA | NA | 74% (39) | 81% (63) | 57† | 13 |
| Ibrutinib (PCYC-1117 / RESONATE17) | Prospective | 17p− | 144 | 64 (IQR 57-72) | 83% (8%) | 70% (NR) | 63% (NR) | 75% (NR) | 28 (IQR 15-28) | 33 |
| Ibrutinib ± rituximab ± bendamustine | Retrospective | 17p− | 34 | NA | NA | 55% (32) | 65% (33) | 28† (14-48) | 20 | |
| CK | 21 | NA | NA | 25% (19) | 55% (25) | |||||
| Ibrutinib CLL Connect USA | “Real-world” | 17p− | 123 | 62 (35-80)† | NA | NA | 64% (36) | NA | 17 (1-60)† | 28 |
| CK | 96 | NA | NA | 55% (29) | NA | |||||
| Idelalisib + rituximab-bendamustine | Prospective | 17p−/ TP53mut | 69 | 62 (38-83)† | 58% (0%) | NA | 29% (11) | NA (NR) | 14 (IQR 7-18)† | 39 |
| Idelalisib + rituximab (0116 trial karyotyped) | Prospective | CK | 26 | 69 (58-84) | 81% (0%) | NA (21) | NA (NR) | 21 | 40 | |
| Idelalisib CLL Connect USA | “Real-world” | 17p− | 17 | 62 (35-80)† | NA | NA | 20% (12) | NA | 17 (1-60)† | 28 |
| CK | 12 | NA | NA | 20% (9) | NA | |||||
| Venetoclax M13-982 extension | Prospective | 17p−/TP53mut | 153 | 67 (29-85) | 77% (18%) | 65% (33) | 53% (26) | 72% (39) | 23 (0-44)‡ | 48 |
| Venetoclax 400mg M12-175, M14-032, M13-982, M13-365 pooled | Pooled prospective | 17p−/ TP53mut | 152 | 76% (17%) | 63% (27) | 51% (25)§ | NA | 16 (0-54)‡ | 16 |
| Agent (study) . | Study type . | Aberration . | n . | Age in years (range) . | ORR (CR)* . | DOR (2 y) (median in mo) . | PFS (2 y) (median in mo) . | OS (2 y) (median in mo) . | Median follow-up, mo (range) . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|
| Ibrutinib (PCYC-1102/1103) | Prospective | 17p− | 34 | 79% (6%) | 31 mo | 57% (26) | 64% (57) | 47 (1-67) | 10 | |
| CK | 37 | 90% (7%) | 39 mo | 65% (33) | 75% (57) | 55 (1-67) | ||||
| Ibrutinib + rituximab | Prospective | 17p− | 21 | 86% (24%) | NA | 55% (32) | 73% (NR) | 47 (36-51)† | 7 | |
| CK | 15 | NA | NA | 55% (32) | 77% (NR) | |||||
| Ibrutinib (NCT01500733) | Prospective | 17p− | 16 | 62 (33-82)† | NA | NA | 74% (39) | 81% (63) | 57† | 13 |
| Ibrutinib (PCYC-1117 / RESONATE17) | Prospective | 17p− | 144 | 64 (IQR 57-72) | 83% (8%) | 70% (NR) | 63% (NR) | 75% (NR) | 28 (IQR 15-28) | 33 |
| Ibrutinib ± rituximab ± bendamustine | Retrospective | 17p− | 34 | NA | NA | 55% (32) | 65% (33) | 28† (14-48) | 20 | |
| CK | 21 | NA | NA | 25% (19) | 55% (25) | |||||
| Ibrutinib CLL Connect USA | “Real-world” | 17p− | 123 | 62 (35-80)† | NA | NA | 64% (36) | NA | 17 (1-60)† | 28 |
| CK | 96 | NA | NA | 55% (29) | NA | |||||
| Idelalisib + rituximab-bendamustine | Prospective | 17p−/ TP53mut | 69 | 62 (38-83)† | 58% (0%) | NA | 29% (11) | NA (NR) | 14 (IQR 7-18)† | 39 |
| Idelalisib + rituximab (0116 trial karyotyped) | Prospective | CK | 26 | 69 (58-84) | 81% (0%) | NA (21) | NA (NR) | 21 | 40 | |
| Idelalisib CLL Connect USA | “Real-world” | 17p− | 17 | 62 (35-80)† | NA | NA | 20% (12) | NA | 17 (1-60)† | 28 |
| CK | 12 | NA | NA | 20% (9) | NA | |||||
| Venetoclax M13-982 extension | Prospective | 17p−/TP53mut | 153 | 67 (29-85) | 77% (18%) | 65% (33) | 53% (26) | 72% (39) | 23 (0-44)‡ | 48 |
| Venetoclax 400mg M12-175, M14-032, M13-982, M13-365 pooled | Pooled prospective | 17p−/ TP53mut | 152 | 76% (17%) | 63% (27) | 51% (25)§ | NA | 16 (0-54)‡ | 16 |
Only studies for which 24-mo estimates were available were considered.
NA, not available; NR, not reached; prosp, prospective; retrosp, retrospective.
Overall response including partial response with persistent lymphocytosis.
Data for the whole sample including patients without TP53 aberrations/complex karyotype.
Time on venetoclax.
Including patients with other doses (150-1200 mg).