- Medicines and Healthcare products Regulatory Agency
- 15 September 2016
- Therapeutic area:
Updated advice for healthcare professionals is available, after conclusion of a review of the safety of idelalisib, including the risk of infection.
Advice for healthcare professionals:
Indications for idelalisib (Zydelig▼)
Chronic lymphocytic leukaemia (CLL):
- combined with rituximab for adults with CLL as first-line treatment in the presence of 17p deletion or P53 mutation in patients who are ineligible for any other therapies (note that this is the updated indication)
- idelalisib continues to be indicated in combination with rituximab for adults with CLL who have received at least one prior therapy
- idelalisib continues to be indicated as monotherapy for adults with follicular lymphoma that is refractory to two previous lines of treatment
Measures to minimise risk of infection in all patients
Pneumocystis jirovecii pneumonia (updated):
- all patients should receive prophylaxis for P jirovecii pneumonia during treatment with idelalisib and for up to 2–6 months after stopping
- duration of post-treatment prophylaxis should be based on clinical judgment, taking into account the patient’s risk factors such as concomitant corticosteroid treatment and prolonged neutropenia
Cytomegalovirus infection (updated):
- regular clinical and laboratory monitoring for cytomegalovirus infection is recommended in patients who are seropositive at the start of treatment with idelalisib or who have other evidence of a history of infection with this virus
- patients with cytomegalovirus viraemia but without signs of infection should be carefully monitored
- for patients with evidence of viraemia and clinical signs of infection, consideration should be given to interrupting idelalisib. Treatment may be restarted if the infection has resolved and if the benefits of resuming are judged to outweigh the risks. If idelalisib treatment is restarted, pre-emptive cytomegalovirus therapy should be considered
General advice about risk of infection (reminder):
- patients should be informed about the risk of serious or fatal infections during treatment
- idelalisib should not be started in patients with any evidence of ongoing systemic bacterial, fungal, or viral infection
- patients should be monitored for respiratory signs and symptoms throughout treatment, and should be advised to promptly report new respiratory symptoms
- absolute neutrophil counts should be monitored in all patients at least every 2 weeks for the first 6 months of treatment, and then at least weekly while count is less than 1000 per mm3. Treatment should be discontinued if absolute neutrophil count falls below 500 per mm3. Treatment can be restarted at a lower dose (100 mg twice daily) when the count rises above 500 per mm3
Results of safety review
In March 2016, an in-depth EU safety review of idelalisib, including serious infection associated with idelalisib, was initiated following a signal from clinical trials. Precautionary, temporary safety measures were implemented and communicated in May 2016. The safety review concluded in July 2016, and updates to treatment recommendations have been made as outlined above. The benefits of idelalisib outweigh the potential risks in all current indications.
Clinical trial signal of infection
3 phase III clinical trials showed a signal of increased serious infection and infection-related mortality associated with idelalisib. The trials were assessing the addition of idelalisib to standard therapy in first-line CLL, and to the treatment of relapsed indolent non-Hodgkin lymphoma (small lymphocytic lymphoma)—ie, outside its currently authorised drug combinations or indicated populations.
The full review has concluded that the study results do not impact on the authorised use of idelalisib. However, data for efficacy and safety are limited in treatment-naive patients with CLL who have a 17p deletion or P53 mutation, and therefore the indication for first-line treatment (combined with rituximab) has been updated to specify patients ineligible for any other therapies.
The risk of serious infection is relevant to all indications and therefore the measures outlined above should be implemented to help minimise this risk.
Reporting of suspected adverse reactions
Suspected adverse reactions should be reported to us on a Yellow Card.
Letter sent to healthcare professionals, August 2016
Article citation: Drug Safety Update volume 10 issue 2, September 2016: 3.
Published: 15 September 2016
Therapeutic area: Cancer