Table 2.
Selected clinical studies with PI3Ki in patients with CLL/SLL.
| Study Regimen | Phase/Name | Population | Number of Patients (Patients with CLL/SLL) | Median Age (Years) | Primary Endpoint | ORR (%) * | CR * | Median PFS * | Median OS * | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| Idelalisib + rituximab vs. rituximab | 3/study 116 | RR-CLL | 220 | 71 | PFS | 85.5 | 1 patient (<1%) | 20.3 months | 40.6 months | [48] |
| Idelalisib + ofatumumab vs. ofatumumab (Study 119) | 3/study 119 | RR-CLL | 261 | 67 | PFS | 75.3 | 1 patient (<1%) | 16.3 months | 20.9 months | [49] |
| Idelalisib + BR vs. placebo + BR | 3 | RR-CLL | 416 | 62 | PFS | 70.0 | 1.4 | 20.8 | NR | [50] |
| Acalabrutinib vs. BR/idelalisib | 3/ ASCEND |
RR-CLL | 398 | 68 | PFS | not reported separately | not reported separately | 16.3 months for investigator choice | NR | [51] |
| Idelalisib + rituximab | 2 | TN-CLL, older patients | 64 | 71 | ORR | 97 | 19% | not reached (36-month 82%) | NR (36-month 90%) | [52] |
| Idelalisib + ofatumumab | 2 | TN-CLL | 27 | 67 | ORR | 88.9% | 1 patient (3.7%) | 23 months | NR (36-month 88%) | [53] |
| Duvelisib | 1/IPI 145-02 | iNHL, TN CLL, RR CLL T-NHL | 210 (75:55 RR; 18 TN) | 67 | Safety, MTD, PK/PD | 56 RR; 83 TN | 1 patient (1.8% of RR CLL) | 15.7 RR NR TN (12 months—94%) |
NR RR (12 months—65.5%) NR TN (12 months—100%) |
[54] |
| Duvelisb | 2/DYNAMO | iNHL double refractory to Rtx and to either Cht or RI | 129 (28) | 65 | ORR | 67.9 | 0 | ND | ND | [55] |
| Duvelisib vs. ofatumumab | 3/DUO | RR-CLL/SLL | 319 | 69 | PFS | 74 | 1 patient (0.6%) | 13.3 | NR (12 months—86%) | [56] |
| Umbralisib | 1 | RR CLL/SLL, RR B-NHL, RR T-NHL, RR HL | 90 (24) | 65 | Safety, MTD, PK | 50 | 0 | 13.4 | ND | [57] |
| Umbralisib + ublituximab (U2) | 1/1b | RR B-NHL, RR CLL/SLL | 75 (22) | 64 | Safety, DLT, MTD | 62 | ND | 27.57 | ND | [58] |
| Umbralisib + ublituximab (U2) vs. O + Chl | 3/UNITY-CLL | TN CLL, RR CLL | 421 (240 TN; 181 RR) | 67 | PFS per IRC | 83.3 | ND | 31.9 (38.5 TN; 19.5 RR) | ND | [59] |
| RETRO-idel | real-world | RR-CLL | 83 | 72 | ORR | 85.5% | NR | 21.7 months | not reached (36-month 55.5%) | [60] |
| RETRO-idel | real-world | TN-CLL | 27 | 71 | ORR | 96.3% | NR | 18.7 months | not reached (36-month 58.6%) | [60] |
B-NHL—B cell non-Hodgkin lymphoma; BR—bendamustine-rituximab; Cht—chemotherapy; CR—complete remission; DTD—dose-limiting toxicity; iNHL—indolent non-Hodgkin lymphoma; IRC—independent review committee; MTD—maximal tolerated dose; ND—no data; NR—not reached; O—ofatumumab; ORR—overall response rate; OS—overall survival; PFS—progression-free survival; R—rituximab; TN-CLL—treatment-naïve chronic lymphocytic leukemia; RR-CLL—relapsed/refractory chronic lymphocytic leukemia; PK pharmacokinetics; PD—pharmacodynamics; Rtx—rituximab; RI—radioimmunotherapy; * data for CLL/SLL cohort; T-NHL—T cell non-Hodgkin lymphoma.