Toxicities associated with idelalisib therapy and a suggested approach to management, based on a synthesis of consensus panel guidelines, US prescribing information, and the recent Gilead safety warning
| Toxicity . | Setting or severity . | Recommendation . |
|---|---|---|
| PJP* | Before initial dosing | All patients should receive prophylaxis with trimethoprim-sulfamethoxazole (dapsone or atovaquone if allergy/intolerance) |
| CMV reactivation* | CMV seronegative | CMV-negative blood products |
| CMV seropositive | Regular (eg, monthly) CMV antigen or PCR monitoring | |
| Symptomatic CMV infection | Stop idelalisib; preemptive ganciclovir (5 mg/kg intravenously twice daily or valganciclovir 900 mg oral twice daily) for 14-21 d and negative test result, or until 2 negative test results | |
| Asymptomatic CMV viremia | Stop idelalisib if viremia increasing; consider preemptive ganciclovir or valganciclovir (see above) | |
| Diarrhea | Mild, moderate | Exclude infection; dietary modifications*; antimotility agents (eg, loperamide) |
| Severe (or unresolved moderate) | Discontinue idelalisib; if infectious cause is excluded, budesonide or prednisone until resolves to grade ≤1; consider redosing at reduced dose (−50 mg) | |
| ALT/AST elevation | 1-3 times ULN | Continue idelalisib; continue to monitor LFTs 2 times weekly |
| >3-5 times ULN | Continue idelalisib; monitor LFTs weekly until <3 times ULN | |
| >5-20 times ULN | Hold idelalisib until ≤1 times ULN; then restart reduced dose (−50 mg) | |
| >20 times ULN | Permanently discontinue idelalisib | |
| Pneumonitis | Mild, persistent cough | Hold idelalisib until etiology has been determined; monitor symptoms; physical examination, CXR, HRCT chest; microbiologic investigations to exclude bacterial/viral infections; clinical review in ≤2 wk; repeat imaging in ≤4 wk |
| Moderate cough or dyspnea | Hold idelalisib until etiology has been determined; monitor symptoms; physical examination, CXR, HRCT chest; consider bronchoscopy and BAL for microbiologic diagnosis including Pneumocystis jirovecii PCR; clinical review in ≤1 wk | |
| Severe (requires oxygen, or ≥5% decrease in baseline oxygen saturation) | Permanent discontinuation of idelalisib; admit to hospital; physical examination, CXR, HRCT chest; bronchoscopy and BAL for microbiologic diagnosis including P. jirovecii PCR; empiric prednisone 1 mg/kg | |
| Neutropenia | 1000-1500/mm3 | Continue idelalisib dosing |
| 500-1000/mm3 | Continue idelalisib dosing; monitor CBC weekly | |
| <500/mm3 | Hold idelalisib; monitor CBC weekly until neutrophil count ≥500/mm3, then restart at 100 mg twice daily |
| Toxicity . | Setting or severity . | Recommendation . |
|---|---|---|
| PJP* | Before initial dosing | All patients should receive prophylaxis with trimethoprim-sulfamethoxazole (dapsone or atovaquone if allergy/intolerance) |
| CMV reactivation* | CMV seronegative | CMV-negative blood products |
| CMV seropositive | Regular (eg, monthly) CMV antigen or PCR monitoring | |
| Symptomatic CMV infection | Stop idelalisib; preemptive ganciclovir (5 mg/kg intravenously twice daily or valganciclovir 900 mg oral twice daily) for 14-21 d and negative test result, or until 2 negative test results | |
| Asymptomatic CMV viremia | Stop idelalisib if viremia increasing; consider preemptive ganciclovir or valganciclovir (see above) | |
| Diarrhea | Mild, moderate | Exclude infection; dietary modifications*; antimotility agents (eg, loperamide) |
| Severe (or unresolved moderate) | Discontinue idelalisib; if infectious cause is excluded, budesonide or prednisone until resolves to grade ≤1; consider redosing at reduced dose (−50 mg) | |
| ALT/AST elevation | 1-3 times ULN | Continue idelalisib; continue to monitor LFTs 2 times weekly |
| >3-5 times ULN | Continue idelalisib; monitor LFTs weekly until <3 times ULN | |
| >5-20 times ULN | Hold idelalisib until ≤1 times ULN; then restart reduced dose (−50 mg) | |
| >20 times ULN | Permanently discontinue idelalisib | |
| Pneumonitis | Mild, persistent cough | Hold idelalisib until etiology has been determined; monitor symptoms; physical examination, CXR, HRCT chest; microbiologic investigations to exclude bacterial/viral infections; clinical review in ≤2 wk; repeat imaging in ≤4 wk |
| Moderate cough or dyspnea | Hold idelalisib until etiology has been determined; monitor symptoms; physical examination, CXR, HRCT chest; consider bronchoscopy and BAL for microbiologic diagnosis including Pneumocystis jirovecii PCR; clinical review in ≤1 wk | |
| Severe (requires oxygen, or ≥5% decrease in baseline oxygen saturation) | Permanent discontinuation of idelalisib; admit to hospital; physical examination, CXR, HRCT chest; bronchoscopy and BAL for microbiologic diagnosis including P. jirovecii PCR; empiric prednisone 1 mg/kg | |
| Neutropenia | 1000-1500/mm3 | Continue idelalisib dosing |
| 500-1000/mm3 | Continue idelalisib dosing; monitor CBC weekly | |
| <500/mm3 | Hold idelalisib; monitor CBC weekly until neutrophil count ≥500/mm3, then restart at 100 mg twice daily |
ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; BAL, bronchoalveolar lavage; CBC, complete blood count; CXR, chest X-ray; HRCT, high-resolution computed tomography; LFTs; liver function tests; ULN, upper limit of normal.
Note that increased risk for opportunistic infection has been reported in phase 3 studies of idelalisib with rituximab ± bendamustine; however, our recommendations around PJP prophylaxis and CMV monitoring should be considered for all patients receiving idelalisib until further safety data are available.