Idelalisib (Zydelig▼): interim measures following signal of serious infection and deaths related to infection found in clinical trials
- Medicines and Healthcare products Regulatory Agency
- 10 May 2016
- Therapeutic area:
- Cancer and Haematology
There are new interim treatment recommendations for idelalisib for chronic lymphocytic leukaemia and follicular lymphoma in light of new findings from clinical trials outside its currently authorised drug combinations or indicated populations.
This article has been superseded
See updated information for idelalisib published September 2016
Interim advice for healthcare professionals:
Chronic lymphocytic leukaemia
- Do not start as first-line treatment in patients who have 17p chromosome deletion or P53 mutation
- For patients who have a 17p deletion or P53 mutation who are already receiving idelalisib first line, clinicians should carefully consider the balance of benefits and risks for the individual (see below), and should decide whether to continue treatment
- Idelalisib combined with rituximab can be started or continued in patients who have received at least one previous line of therapy
- Idelalisib monotherapy can be started or continued in adults with disease refractory to two previous lines of treatment
New measures to minimise risk for all patients
- Inform patients of the risk of serious and fatal infections (see below)
- Do not start treatment in patients with any evidence of ongoing systemic bacterial, fungal, or viral infection
- All patients should receive prophylactic treatment for Pneumocystis jirovecii pneumonia throughout idelalisib treatment
- There should be regular clinical and laboratory screening for cytomegalovirus infection. Stop treatment in patients with evidence of infection or viraemia
- Monitor patients for signs and symptoms of respiratory disease throughout treatment and advise them to promptly report any new respiratory symptoms
- Monitor absolute neutrophil counts in all patients at least every 2 weeks for the first 6 months of treatment, and at least weekly in those with a count fewer than 1000 per mm3 (further guidance is provided in a table in a letter to healthcare professionals)
Reporting of suspected adverse reactions
- Suspected adverse reactions should be reported to us on a Yellow Card
Interim results from clinical trials
3 phase III clinical trials have shown a signal of increased mortality associated with idelalisib. The trials were assessing the addition of idelalisib to standard therapy in first-line chronic lymphocytic leukaemia and to the treatment of relapsed indolent non-Hodgkin lymphoma (small lymphocytic lymphoma)—ie, outside its currently authorised drug combinations or indicated populations. The relevance of these findings for the licensed uses of idelalisib is currently under assessment.
The trials showed increased numbers of deaths in the idelalisib treatment group compared with placebo (7.4% vs 3.5%, respectively). The excess deaths were mainly due to infections, including P jirovecii and cytomegalovirus, and respiratory events (some of which may have been related to infection).
The precautionary measures outlined above should be followed while there is further investigation of the implications of these findings for the medicine’s authorised uses. Further advice will be communicated as appropriate at the end of the review.
Letter sent to healthcare professionals 23 March 2016
Article citation: Drug Safety Update Vol 9 issue 10 May 2016 3.
Published: 10 May 2016