(233) Cytomegalovirus Infection Reactivation in Multiple Myeloma Patients Administered Proteasome Inhibitor-Combination Therapy: A Disproportionality Analysis in a Spontaneous Reporting Database

Sunday, August 28, 2022

8:00 AM – 1:45 PM CEST

Location: Hall C

Publication Number: 1278

Presenting Author(s)

Gursimran Kaur, PharmD
– Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India

Co-Author(s)

Lipin Lukose, PharmD
– Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India
Beulah E. Thomas
– Hemato-oncology clinical pharmacist and Bone marrow transplant co-ordinator, Sparse Hospital, Bengaluru, Karnataka, Karnataka, India
Subeesh Kulangara Viswam, MPharm
– Assistant Professor, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi, Karnataka, India

Background: Treatment for multiple myeloma (MM) with proteasome inhibitors may result in the onset or reactivation of cytomegalovirus (CMV) infection. However, research into the topic is limited.

Objectives: To analyse the CMV reactivation in MM patients on proteasome inhibitor-based therapy through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database.

Methods: A retrospective case/non-case disproportionality analysis was performed using the FAERS database. The data was curated and analysed using a web-based tool called Open Vigil 2.1(2008Q1-2021Q3). The preferred term used for the study was "cytomegalovirus infection reactivation," and the drugs included in the analysis were Bortezomib, Carfilzomib, and Ixazomib. Proportional Reporting Ratio (PRR) and Reporting odds ratio (ROR) were used as the analysis data mining algorithm. A value of ROR-1.96SE>1 and PRR≥2 with an associated X2 value of 4 or more was considered the threshold for a signal.

Results: FAERS database had a total of 356 reports on CMV infection reactivation, out of which 45 reports were associated with proteasome inhibitors (PI's). Positive signals were obtained for bortezomib [(ROR 34.1(95%CI= 24.4-47.8) and PRR 34.1(25.4-47.7)], and carfilzomib [(ROR 22.1(95%CI= 10.5-46.8) and PRR 22.1(10.5-46.7)] associated CMV infection reactivation. The observed data unveiled that females exhibited a greater PRR value of 1.6 times than males on bortezomib therapy. Stratification of age groups revealed that adults (18-64 years) reported a higher PPR value (63.3) than geriatric (65-100 years) patients (25.7) on the same therapy. Eight deaths and 4 cases linked to a life-threatening adverse event were reported for bortezomib. Upon analysis, hospitalization for bortezomib (13) and carfilzomib (6) therapy were also reported.

Conclusions: The signal for CMV infection reactivation with bortezomib and carfilzomib was detected using a spontaneous reporting data system, but studies investigating the immune profile of patients administered PI- regimens are required to identify high-risk subgroups for CMV reactivation.