Reasons for underreporting of VAEs in CML patients treated with BCR/ABL1 TKIs
| Reasons . |
|---|
| Primary |
| Relatively high incidence of atherosclerosis and VAEs worldwide. |
| Relatively low patient numbers per center participating in clinical trials. |
| Only a very few drugs are known to promote atherosclerosis, and only a very few drugs used to treat hematologic neoplasms may promote VAE development. |
| The initial clinical trials were not powered for the detection of VAEs. |
| Most clinical trials excluded patients with severe cardiac and/or metabolic comorbidities. |
| Secondary |
| Latency period of several months to years before VAEs develop during TKI therapy. |
| CML centers and local experts are not trained to detect and to manage VAEs. |
| VAEs are not “oncologic”: therefore, VAE patients were neither reported nor referred back to the oncologist by the practitioners. Also, the patients did not report for the same reason and because of the general incidence. |
| Other |
| Major papers published in top journals did not report on VAE development. |
| Initially, nilotinib was reported as an extremely safe TKI without side effects. |
| In major and special meetings, TKIs were long reported as safe without an impact on development of vascular diseases. |
| Clinically silent vascular events in diabetic patients may be overlooked. |
| Sudden death before a cerebral or cardiac VAE was detected. |
| Reasons . |
|---|
| Primary |
| Relatively high incidence of atherosclerosis and VAEs worldwide. |
| Relatively low patient numbers per center participating in clinical trials. |
| Only a very few drugs are known to promote atherosclerosis, and only a very few drugs used to treat hematologic neoplasms may promote VAE development. |
| The initial clinical trials were not powered for the detection of VAEs. |
| Most clinical trials excluded patients with severe cardiac and/or metabolic comorbidities. |
| Secondary |
| Latency period of several months to years before VAEs develop during TKI therapy. |
| CML centers and local experts are not trained to detect and to manage VAEs. |
| VAEs are not “oncologic”: therefore, VAE patients were neither reported nor referred back to the oncologist by the practitioners. Also, the patients did not report for the same reason and because of the general incidence. |
| Other |
| Major papers published in top journals did not report on VAE development. |
| Initially, nilotinib was reported as an extremely safe TKI without side effects. |
| In major and special meetings, TKIs were long reported as safe without an impact on development of vascular diseases. |
| Clinically silent vascular events in diabetic patients may be overlooked. |
| Sudden death before a cerebral or cardiac VAE was detected. |