Table 1.
Assessment of clinical evidence of risk of infections and corresponding references.
| KINASE INHIBITOR TREATMENT REGIMEN | PATHWAY | UNDERLYING MALIGNANCY | SIGNIFICANT EVIDENCE OF KI-ASSOCIATED INFECTIOUS COMPLICATIONSɣ | ALL GRADE INFECTIONS/GRADE 3/4 INFECTION INCLINICAL TRIALS [%] | REFERENCE(S)€ |
|---|---|---|---|---|---|
| Imatinib | BCR-ABL, c-KIT | CML | Minor | 15/0,2 | 9 |
| GIST | None | 11/0 | 167 | ||
| Ph+-ALL | Minor | N/A. /38–52 (combined w. chemotherapy) | 168 169 | ||
| Dasatinib | BCR-ABL, c-KIT | CML | Minor | 10.5/2 | 33 |
| Ph+-ALL | Minor | 18/8 | 37 | ||
| Nilotinib | BCR-ABL | CML | None | 9/1 | 31 |
| Ph+-ALL | None | N/A. | N/A. | ||
| Bosutinib | BCR-ABL | CML | None | 12/0 | 39 |
| Ponatinib | BCR-ABL | CML | None | 6/6 | 40 |
| Ph+-ALL | None | 6/6 | 40 | ||
| Erlotinib | EGFR | NSCLC | None | 5/1 | 53 |
| Gefitinib | EGFR | NSCLC | None | N/A./3 | 54 |
| Afatinib | EGFR | NSCLC | None | 0/0 | 42 |
| Crizotinib | ALK-4-EML | NSCLC | None | 32/0 | 47 |
| ALK-pos. NHL | None | N/A/0 | 48 | ||
| Ceritinib | ALK4-EML | NSCLC | None | N/A./0 | 57 |
| Vemurafenib | BRAF | Melanoma | None | 0/0* | 64 |
| Dabrafenib | BRAF | Melanoma | None | 0/0* | 170 |
| Trametinib§ | MEK | Melanoma | None | 0/0* | 60 |
| Temsirolimus | mTOR | MCL | Major | 25/7 | 102 |
| RCC | Major | 27/5 | 103 | ||
| Everolimus | mTOR | RCC | Major | 37/13 | 105 |
| pNET | Major | N/A./5 | 171 | ||
| TB | Major | 22/14 | 172 | ||
| Hs BRCA$ | Major | 9–15/N/A. | 110 | ||
| Sunitinib | Multikinase | RCC | None | 0/0* | 173 |
| pNET | None | 0/0* | 174 | ||
| GIST | None | 0/0* | 175 | ||
| Sorafenib | Multikinase | RCC | None | 0/0* | 128 |
| HCC | None | 0/0* | 176 | ||
| FLT3-pos. AML¥ | Moderate | N/A./55 | 130 | ||
| Regorafenib | Multikinase | CRC | None | 10/1 | 132 |
| GIST | None | 0/0* | 133 | ||
| Pazopanib | Multikinase | STS | None | 0/0* | 177 |
| RCC | None | 0/0* | 138 | ||
| Axitinib | Multikinase | RCC | None | 0/0* | 178 |
| Ruxolitinib | JAK2 | MF | Major | 50/N/A. | 179 |
| PV | Major | 42/4 | 73 | ||
| Tofacitinib | JAK3 | RA | Major | 23/5 | 180 |
| Ibrutinib | BTK | CLL | Major | 33/12 | 157 |
| MCL | Major | 23/6 | 145 | ||
| Idelalisib | PIK3delta | CLL# | Major | 28/19 | 164 |
| NHL | Major | 25/7 | 146 |
Notes: Kinase inhibitors are shown according to target/indication.
Graded to none, minor, moderate, and major.
Infectious complications were not mentioned in the safety data or the supplements.
In combination with dabrafenib.
In combination with rituximab.
If possible randomized trial.
Combined with chemotherapy.
In combination with exemestan.
Abbreviations: CML, chronic myeloid leukemia; GIST, gastrointestinal stromal tumor; Ph+-ALL, Philadelphia-chromosome-positive acute lymphoblastic leukemia; NSCLC, non-small cell lung cancer; ALK-pos. NHL, ALK-positive non-Hodgkin’s lymphoma; MCL, mantle cell lymphoma; RCC, renal cell cancer; pNET, pancreatic neuroendocrine tumor; TB, subependymal giant cell astrocytoma associated with tuberous sclerosis; Hs BRCA, hormone-sensitive breast cancer; HCC, hepatocellular carcinoma; AML, acute myeloid leukemia; CRC, colorectal carcinoma; STS, soft-tissue sarcoma; MF, myelofibrosis; PV, polycythemia vera; RA, rheumatoid arthritis; CLL, chronic lymphocytic leukemia.