Table 3.
Summary of non-hematological characteristic PI3Ki-related adverse events across selected studies.
| Study | Population | Diarrhea Colitis (All Grade/Grade ≥ 3) |
ALT Increase AST Increase (All Grade/Grade ≥ 3) |
Infections/Pneumonia (All Grade/Grade ≥ 3) | Pneumonitis (All Grade/Grade ≥ 3) | Cutaneous Adverse Events (All Grade/Grade ≥ 3) | Drug Discontinuation Due to AEs | References |
|---|---|---|---|---|---|---|---|---|
| Phase 3 idelalisib + rituximab vs. rituximab (Study 116) | RR-CLL | 46.4%/16.4% 10.9%/8.2% | 39.1%/9.1% 28.2%/5.5% |
NR/32.7% NR/NR |
10%/6.4% | 10%/3% | 5% | [48] |
| Phase 3 idelalisib + ofatumumab vs. ofatumumab (Study 119) | RR-CLL | 53%/19% 6%/6% |
53%/11% 37%/9% |
78%/NR 19%/14% |
6%/5% | 18%/2% | 39% | [49] |
| Phase 3 idelalisib + BR vs. placebo + BR | RR-CLL | 38%/9.2% 6%/6% |
61%/21% 53.5%/15.5% |
69%/39% 17%/1% |
NR/1.4% | 16%/3% | 27% | [50] |
| Phase 2 idelalisib + rituximab in older patients | TN-CLL | 64%/42% (diarrhea + colitis) | 67%/23% (ALT + AST) | 44%/25% 28%/19% |
3%/3% | 58%/13% | 29.7% | [52] |
| Phase 2 idelalisib + ofatumumab | TN-CLL | 46%/17% (diarrhea + colitis) | 79%/54% (ALT + AST) | 13%/13% NR/NR |
13%/8% | NR/R | Study prematurely terminated due to AEs | [53] |
| Phase 1 Duvelisib (IPI 145 -2 trial) |
iNHL, TN CLL, RR CLL, T-NHL | 42%/11.4% NR/6% |
38.6%/19.3% 37.6%/15.3% |
NR/NR 13.3%/9.5% |
NR/4% | 30.5%/5.7% | NR | [54] |
| Phase 2, (DYNAMO trial) | iNHL | 48.8%/14.7% 7.8%/5.4% |
14%/5.4% 10.1%/3.1% |
NR/NR | 4.7%/NR | NR/NR | 31% | [55] |
| Phase 3, duvelisib vs. ofatumumab (DUO trial) | RR-CLL | 51%/15% 13%/12% |
NR/3% NR/3% |
69%/NR 18/%14% |
NR/3% | 10%/2% | NR | [56] |
| Phase 1 umbralisib | RR CLL/SLL, RR B-NHL, RR T-NHL, RR HL | 40%/3% 2%/2% |
3%/2% 4/%3% |
NR/NR 8%/6% |
NR/NR | 14%/4% | 7% | [57] |
| Phase1/1b umbralisib + ublituximab | RR B-NHL, RR CLL/SLL | 64%/0% NR/NR |
14%/0% 14%/0% |
96%/5% 9%/5% |
NR/NR | NR/NR | 13% | [58] |
| Phase 3 umbralisib + ublituximab (UNITY-CLL) | TN CLL, RR CLL | NR/12.1% NR/3.4% |
NR/8.3% (ALT + AST) | NR/NR | NR/2.9% | NR/NR | 16.5% | [59] |
B-NHL—B cell non-Hodgkin lymphoma; BR—bendamustine-rituximab; CR—complete remission; NR—not reported; O—ofatumumab; ORR—overall response rate; OS—overall survival; PFS—progression-free survival; R—rituximab; RR-CLL—relapsed/refractory chronic lymphocytic leukemia; TN-CLL—treatment-naïve chronic lymphocytic leukemia; T-NHL—T cell non-Hodgkin lymphoma; iNHL—indolent non-Hodgkin lymphoma.