From the Guidelines
Venclexta (venetoclax) is associated with an increased risk of infections, particularly febrile neutropenia, pneumonia, and sepsis, due to its mechanism of action as a BCL-2 inhibitor and its effects on the immune system, as reported in a 2022 study published in Leukemia 1.
Infection Risk and Mechanism
The risk of infection is higher in patients with acute myeloid leukemia (AML) or chronic lymphocytic leukemia (CLL), especially those with neutropenia. Venclexta's action as a BCL-2 inhibitor can lead to neutropenia by affecting white blood cell production and survival.
Monitoring and Prophylaxis
Patients taking Venclexta should be monitored closely for signs of infection, particularly during the first few months of treatment.
- Common infections associated with Venclexta include pneumonia, upper respiratory tract infections, and sepsis.
- Prophylactic antimicrobials may be recommended for high-risk patients, though specific regimens vary based on individual risk factors, as suggested by the European Conference on Infections in Leukemia (ECIL) guidelines 1.
- Consider antibacterial and antifungal prophylaxis when hypomethylating agents are combined with venetoclax, as recommended by ECIL guidelines 1.
Management of Infections
Patients should promptly report fever, chills, cough, or other signs of infection to their healthcare provider.
- Regular blood count monitoring is essential during treatment.
- Dose modifications or temporary discontinuation may be necessary if severe infections occur, as recommended by ECIL guidelines 1.
- Consider dose interruptions to allow for hematologic recovery in patients with a response, and promote appropriate interruptions in venetoclax between treatment cycles to augment hematologic recovery 1.
From the FDA Drug Label
In patients with CLL/SLL, administration of posaconazole during initiation and the ramp-up phase of venetoclax is contraindicated ... Concomitant administration of posaconazole, a strong CYP3A4 inhibitor, with venetoclax may increase venetoclax toxicities, including the risk of ... serious infections. The association between Venclexta (Venetoclax) and infection is that concomitant administration of a strong CYP3A4 inhibitor, such as posaconazole, with venetoclax may increase the risk of serious infections 2.
- Key points:
- Concomitant use of posaconazole and venetoclax may increase the risk of serious infections.
- Dose reduction and safety monitoring are recommended when coadministering posaconazole with venetoclax.
From the Research
Association between Venclexta (Venetoclax) and Infection
- The use of Venetoclax has been associated with an increased risk of infections, particularly in patients with acute myeloid leukemia (AML) 3, 4, 5, 6.
- A study found that AML patients treated with Venetoclax-based therapy had a 13.2% incidence of Pneumocystis jirovecii pneumonia (PJP), a potentially life-threatening infection 3.
- Another study reported that Venetoclax was associated with a high probability of increased risk of high-grade neutropenia and febrile neutropenia in AML patients 4.
- Common infectious complications in AML patients treated with Venetoclax include fever without an identifiable source, clinically documented infections, and microbiologically documented infections 5.
- The most commonly isolated organisms in culture were Candida albicans, Klebsiella pneumonia, and Pseudomonas aeruginosa 5.
- Risk factors for infectious complications in AML patients treated with Venetoclax include a high proportion of blasts in bone marrow, decreased hemoglobin level, and fever with or without a documented infection at baseline 5.
- The use of mold-active antifungal agents as antifungal prophylaxis may be necessary, particularly in patients with secondary or therapy-related AML 6.
Types of Infections
- Pneumocystis jirovecii pneumonia (PJP) 3
- Invasive fungal infections (IFIs) caused by Aspergillus 6
- Bloodstream infections (BSIs) 6
- Candida albicans, Klebsiella pneumonia, and Pseudomonas aeruginosa infections 5