Results of novel drugs in R/R CLL (selected for longest follow-up)
| Agent/Regimen . | Target . | No. of patients . | Risk group (17p-) . | ORR* (%) . | CR (%) . | PFS (%) . | OS (%) . | Discontinued due to PD (% Richter) . | Mortality in the absence of PD (%) (NRM) . | Remained on study drug at last follow-up (%) . | Follow-up, mo . | Ref. . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Status . | % 17p- . | Median . | Range . | |||||||||||
| Ibrutinib (PCYC 1102 trial) | BTK | 85 | R/R† | 33 | 71/88 68 (17p-) | 2 | 75 (24 mo) 57 (17p-) 93 (no 17p-, no 11q-) (P = .04) | 83 (24 mo) 70 (17p-) 93 (no 17p-, no 11q-) (P = .15) | 13 (63) | 6 | 64 | 21 | 1-27 | 13 |
| Ibrutinib (PCYC-1103/PCYC-1102 extension trial) | BTK | 101 | R/R† | 34 | 76/81 56 (17p-) | NA | 68 (30 mo) 46 (30 mo; 17p-) | 80 (30 mo) 66 (30 mo; 17p-) | NA | NA | 29 mo‡ 27mo (17p-)‡ | 36 | 58 | |
| Ibrutinib (PCYC-1112 trial) | BTK | 195 | R/R† | 32 | 43/63 | NA | 88 (6 mo) 83 (6 mo; 17p-) | 90 (12 mo) | 5 (22) | NA | 86 | 9 | 0.1-17 | 59 |
| Ibrutinib + rituximab | BTK | 40 | High-risk§ | 33 (del[17p]/TP53mut) | 90/100 | 10 | 78 (18 mo) 72 (del[17p]/TP53mut) 84 (no 17p-/TP53wt) | 84 (18 mo) | 8 | 8 | 78 (70) | 17 | 56 | |
| Ibrutinib + rituximab-bendamustin | BTK | 30 | R/R† | 23 | 93 | 17 | 78 (15 mo) | NA | 8 | NA | 70|| | 16 | 60 | |
| CC-292 | BTK | 66 | R/R† | 22 | 40/NA 25 (17p-) | NA | NA | NA | NA | NA | 73 (47) | 11 | 61 | |
| Idelalisib + rituximab or ofatumumab | PI3Kδ | 40 | R/R† | 28 (del[17p]/ TP53mut) | 83/NA 73 (del[17p]/TP53mut) | 8 | 20 mo 19 mo (del[17p]/TP53mut) | NR | 25 | 8 | 35 (NA) | 18 | 0-33 | 57 |
| Idelalisib + rituximab/BF or C | PI3Kδ | 45 | R/R | 42 (del[17p]/ TP53mut) | 78/NA 70 (del[17p]/TP53mut) 83 (no 17p-/TP53wt) | 2 | 29 mo | NR | NA | NA | 40 (NA) | 12 | 0-33 | 63 |
| Idelalisib monotherapy | PI3Kδ | 54 | R/R | 24 (del[17p]/ TP53mut) | 39/72 | 0 | 32 mo¶ 5 mo¶ (del[17p]/TP53mut 41 mo¶ (no 17p-/TP53wt) | 75 (36 mo) | 46 | 13 | 15 | NA | 14 | |
| Idelalisib pooled analysis of monotherapy (n = 54) and combinations (R, B, BR, O, F, Chl, ChlR; n = 114) | PI3Kδ | 168 | R/R | 27 (del[17p]/ TP53mut) | 80/NA 67 (del[17p]/TP53mut) 83 (no 17p-/TP53wt) | 5 | 24 mo# 19 mo (del[17p]/TP53mut) 32 mo (no 17p-/TP53wt) | NR | NA | NA | NA | NA | 64 | |
| IPI-145 | PI3Kγδ | 52 | R/R | 53 (del[17p]/ TP53mut) | 47/NA 50 (del[17p]/TP53mut) | 5 | NA | NR | NA | NA | 50 | 5 | 65 | |
| ABT-199 | BCL2 | 84 | R/R | 23 | 79 78 (17p-) | 22 | 21 mo# | NA | 21 (NA) | NA | 67 | 15 | 0.5-29 | 62 |
| Agent/Regimen . | Target . | No. of patients . | Risk group (17p-) . | ORR* (%) . | CR (%) . | PFS (%) . | OS (%) . | Discontinued due to PD (% Richter) . | Mortality in the absence of PD (%) (NRM) . | Remained on study drug at last follow-up (%) . | Follow-up, mo . | Ref. . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Status . | % 17p- . | Median . | Range . | |||||||||||
| Ibrutinib (PCYC 1102 trial) | BTK | 85 | R/R† | 33 | 71/88 68 (17p-) | 2 | 75 (24 mo) 57 (17p-) 93 (no 17p-, no 11q-) (P = .04) | 83 (24 mo) 70 (17p-) 93 (no 17p-, no 11q-) (P = .15) | 13 (63) | 6 | 64 | 21 | 1-27 | 13 |
| Ibrutinib (PCYC-1103/PCYC-1102 extension trial) | BTK | 101 | R/R† | 34 | 76/81 56 (17p-) | NA | 68 (30 mo) 46 (30 mo; 17p-) | 80 (30 mo) 66 (30 mo; 17p-) | NA | NA | 29 mo‡ 27mo (17p-)‡ | 36 | 58 | |
| Ibrutinib (PCYC-1112 trial) | BTK | 195 | R/R† | 32 | 43/63 | NA | 88 (6 mo) 83 (6 mo; 17p-) | 90 (12 mo) | 5 (22) | NA | 86 | 9 | 0.1-17 | 59 |
| Ibrutinib + rituximab | BTK | 40 | High-risk§ | 33 (del[17p]/TP53mut) | 90/100 | 10 | 78 (18 mo) 72 (del[17p]/TP53mut) 84 (no 17p-/TP53wt) | 84 (18 mo) | 8 | 8 | 78 (70) | 17 | 56 | |
| Ibrutinib + rituximab-bendamustin | BTK | 30 | R/R† | 23 | 93 | 17 | 78 (15 mo) | NA | 8 | NA | 70|| | 16 | 60 | |
| CC-292 | BTK | 66 | R/R† | 22 | 40/NA 25 (17p-) | NA | NA | NA | NA | NA | 73 (47) | 11 | 61 | |
| Idelalisib + rituximab or ofatumumab | PI3Kδ | 40 | R/R† | 28 (del[17p]/ TP53mut) | 83/NA 73 (del[17p]/TP53mut) | 8 | 20 mo 19 mo (del[17p]/TP53mut) | NR | 25 | 8 | 35 (NA) | 18 | 0-33 | 57 |
| Idelalisib + rituximab/BF or C | PI3Kδ | 45 | R/R | 42 (del[17p]/ TP53mut) | 78/NA 70 (del[17p]/TP53mut) 83 (no 17p-/TP53wt) | 2 | 29 mo | NR | NA | NA | 40 (NA) | 12 | 0-33 | 63 |
| Idelalisib monotherapy | PI3Kδ | 54 | R/R | 24 (del[17p]/ TP53mut) | 39/72 | 0 | 32 mo¶ 5 mo¶ (del[17p]/TP53mut 41 mo¶ (no 17p-/TP53wt) | 75 (36 mo) | 46 | 13 | 15 | NA | 14 | |
| Idelalisib pooled analysis of monotherapy (n = 54) and combinations (R, B, BR, O, F, Chl, ChlR; n = 114) | PI3Kδ | 168 | R/R | 27 (del[17p]/ TP53mut) | 80/NA 67 (del[17p]/TP53mut) 83 (no 17p-/TP53wt) | 5 | 24 mo# 19 mo (del[17p]/TP53mut) 32 mo (no 17p-/TP53wt) | NR | NA | NA | NA | NA | 64 | |
| IPI-145 | PI3Kγδ | 52 | R/R | 53 (del[17p]/ TP53mut) | 47/NA 50 (del[17p]/TP53mut) | 5 | NA | NR | NA | NA | 50 | 5 | 65 | |
| ABT-199 | BCL2 | 84 | R/R | 23 | 79 78 (17p-) | 22 | 21 mo# | NA | 21 (NA) | NA | 67 | 15 | 0.5-29 | 62 |
B, bendamustin; BR, bendamustin-rituximab; Chl, chlorambucil; ChlR, chlorambucil-rituximab; CR, complete response; F, fludarabine; mut, mutation; O, ofatumumab; PD, progressive disease; PI3Kg, phosphatidylinositol 3-kinase g; PI3Kd, phosphatidylinositol 3-kinase d; R; rituximab; wt, wild-type.
Overall response (according to International Workshop on Chronic Lymphocytic Leukemia10 )/overall response including partial response with persistent lymphocytosis.
Relapsed and/or refractory.
Median time on study and 17p- patients, respectively.
del(17p)/TP53-mutated, PFS less than 36 mo after first-line chemoimmunotherapy, and/or relapsed disease with 11q-. Four patients were treatment-naïve.
Five patients discontinued in favor of proceeding to HSCT.
For the 28 patients who were treated with ≥150 mg twice daily.
Duration of response.