“Given the importance of T cell function in the pathogenesis of opportunistic infections, especially cryptococcosis and PJP, it is plausible that ibrutinib’s off-target ITK inhibition is a contributing factor in the development of opportunistic infections,” the authors noted.

Citing the incidence of fungal infections among patients on ibrutinib, a separate, international team of researchers called for increased surveillance of opportunistic infection during clinical trials.2 The Mayo Clinic team also called for post-marketing surveillance of opportunistic infections among patients receiving ibrutinib.

“Prophylactic antimicrobials are now recommended when initiating patients on idelalisib, but not ibrutinib [because of possible drug-drug interactions],” the authors wrote. “We recommend close monitoring of patients initiating ibrutinib therapy and individualized prophylaxis while recognizing the increased risk of fungal and P. jirovecii infections.”

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The Mayo Clinic team also advised baseline hepatitis B virus (HBV) serology labs for patients starting ibrutinib therapy and vaccination against influenza and S. pneumoniae. Patients with chronic HBV should be considered for prophylactic entecavir (0.5 mg daily by mouth), they noted.

The herpes zoster vaccine “appears to be safe in immunocompromised individuals and is likely to become a standard preventive strategy,” the authors wrote.However, the need for antimicrobial prophylaxis is still warranted regardless of vaccination status.” They identified assessment of the long-term efficacy and safety of that vaccine among patients with CLL as a research priority.

References

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  2. Chamilos G, Lionakis MS, Kontoyiannis DP. Call for action: invasive fungal infections associated with ibrutinib and other small molecule kinase inhibitors targeting immune signaling pathways. Clin Infect Dis. 2018;66:140-8.
  3. Scarfo L, Ferreri AJM, Ghia P. Chronic lymphocytic leukaemia. Crit Rev Oncol Hematol. 2016;104:169-82.
  4. Hallek M, Shanafelt TD, Eichhorst B. Chronic lymphocytic leukaemia. Lancet. 2018 Feb 21. doi: 10.1016/S0140-6736(18)30422-7 [Epub ahead of print]
  5. Kreiniz N, Bejar J, Polliack A, Tadmor T. Severe pneumonia associated with ibrutinib monotherapy for CLL and lymphoma. Hematol Oncol. 2018;36:349-54.
  6. Varughese T, Ying T, Cohen N, et al. Serious infections in patients receiving ibrutinib for treatment of lymphoid malignancies. Clin Infect Dis. 2018 March 2. doi: 10.1093/cid/ciy175 [Epub ahead of print]
  7. Arthurs B, Wunderle K, Hsu M, Kim S. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia. Respir Med Case Rep. 2017; 21:27-9.
  8. Giridhar K, Shanafelt T, Tosh PK, Parikh SA, Call TG. Disseminated herpes zoster in chronic lymphocytic leukemia (CLL) patients treated with B-cell receptor pathway inhibitors. Leuk Lymphoma. 2017;58:1973-6.