Cytomegalovirus reactivation after bortezomib treatment for multiple myeloma and light chain amyloidosis

Abstract

Objective Cytomegalovirus (CMV) is an opportunistic herpesvirus, and reactivation of infection is possible in immunocompromised patients. Historically, the risk for haematology patients is restricted to those treated with an allogeneic transplant or T‐cell depleting agents. Bortezomib is a highly efficacious proteasome inhibitor widely used to treat multiple myeloma and light chain (AL) amyloidosis patients. The objective of this small prospective study was to quantify the risk of CMV reactivation associated with bortezomib treatment. Methods Fifty‐seven consecutive multiple myeloma or AL amyloidosis patients commencing bortezomib‐based therapy were included. Viral copy numbers were established at baseline and then at fortnightly intervals during treatment. Pre‐emptive anti‐viral treatment was initiated in patients with a viral load >7500 copies/mL. Results Reactivation of CMV was detected in 39% (n = 12/31) of seropositive bortezomib treated patients compared with 0% of CMV seronegative patients. Detectable DNAemia developed during the first two cycles of treatment in 83% (n = 10/12) patients. Anti‐viral treatment was initiated in 42% (n = 5/12), but no cases of active CMV disease were seen. Conclusion This study suggests that there is a substantial risk of CMV reactivation in CMV‐seropositive plasma cell dyscrasia patients treated with bortezomib.

Bortezomib and rituximab in de novo adolescent/adult CD20-positive, Ph-negative pre-B-cell acute lymphoblastic leukemia

“…28 The higher incidence may be due to the T-cell immunosuppressive effects of bortezomib. 29 This study, which enrolled a uniform cohort of patients and performed MRD assessment in all evaluable patients, could achieve its primary end point of improving the MRD rates postinduction. There was a trend toward improvement in survival; however, given the phase 2 design, it needs to be explored further.…”

T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy

“…67,68 Although the impact of BCD treatment alone on T cells is yet to be determined in AL patients, the similar risk of cytomegalovirus reactivation in bortezomibtreated MM and AL patients suggests that bortezomib may induce similar T cell changes in AL patients. 69,70 In addition, in the patients who got an early and deep response, 71 the samples after only one cycle of Dara-based therapy should be collected to study an early T cell immune response. Prolonged IFNG signalling is well known to induce the expression of immune checkpoint molecules such as PD-L1, thus resulting in tumour immunoevasion.…”

“… 67 , 68 Although the impact of BCD treatment alone on T cells is yet to be determined in AL patients, the similar risk of cytomegalovirus reactivation in bortezomib‐treated MM and AL patients suggests that bortezomib may induce similar T cell changes in AL patients. 69 , 70 …”

Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID‐19 pandemic

“…Bortezomib and other proteasome inhibitors (ixazomib, carfilzomib) are associated with increased risk of viral infections (e.g. varicella zoster virus reactivation and perhaps cytomegalovirus) 79 . Patients on bortezomib may also present with pulmonary infiltrates and fever due to hypersensitivity pneumonia, 80,81 and should be kept in the differential diagnosis when other infectious causes are excluded (including COVID‐19).…”

“…varicella zoster virus reactivation and perhaps cytomegalovirus). 79 Patients on bortezomib may also present with pulmonary infiltrates and fever due to hypersensitivity pneumonia, 80,81 and should be kept in the differential diagnosis when other infectious causes are excluded (including COVID-19). Immunomodulatory drugs (IMiDs) are also associated with increased risk of pulmonary infections and thrombotic complications, 82 as well as pneumonitis.…”