Idelalisib (Zydelig) should not be used in combination with rituximab in a range of patients with haematological malignancies, the TGA advises.
The alert follows serious adverse events, including death, in patients receiving idelalisib and other cancer medicines as part of a phase 3 clinical trial which has since been discontinued.
Patients with chronic lymphocytic leukaemia or relapsed indolent non-Hodgkin’s lymphoma who received idelalisib had a higher mortality rate than control patients (7.4% v 3.5%).
Deaths often occurred due to infection such as sepsis and pneumonia within 180 days of starting treatment.
A review by the TGA found the risk was also relevant to some of the previously approved uses for the medicine.
The TGA concluded idelalisib should no longer be indicated in combination with rituximab as a first-line treatment in CLL/small lymphocytic lymphoma patients in the presence of 17p deletion or TP53 mutation.
Additional clarifications to the indications include:
- Extension of the indication in CLL/SLL to include use in combination with ofatumumab in adult CLL/SLL patients upon relapse in patients for whom chemoimmunotherapy is not considered suitable.
- Revision of the indication in follicular lymphoma (FL) to specify that the disease must be refractory to both rituximab and an alkylating agent.
The revised indications are:
- Zydelig in combination with rituximab is indicated for the treatment of adult patients with CLL/SLL upon relapse in patients for whom chemo-immunotherapy is not considered suitable.
- Zydelig in combination with ofatumumab is indicated for the treatment of adult patients with CLL/SLL upon relapse in patients for whom chemo-immunotherapy is not considered suitable.
- Zydelig is indicated as monotherapy for the treatment of patients with FL which is refractory to at least two prior systemic therapies. The disease must be refractory to both rituximab and an alkylating agent.
A boxed warning has been added to the Product Information (PI) regarding the risk of serious infections with specific reference to Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) infection and also pneumonitis.
Risk minimisation strategies include prophylaxis for PJP during and for up to six months after treatment with idelalisib and monthly clinical and laboratory monitoring for CMV infection in some patients.