Hepatitis B (HBV) Reactivation Rate and Fate Among Multiple Myeloma Patients Receiving Lenalidomide Containing Regimens: A Single Center Experience
Authors: Ataca Pinar , Atilla Erden , Kircali Ekin , Idilman Ramazan , Beksac Meral 
Published: October 2019

Abstract
Introduction: Reactivation of HBV refers to an increase in hepatitis B virus replication in a patient with inactive or resolved HBV. Reactivation of HBV replication has been reported in 20% to 50% of untreated HBV carriers undergoing immunosuppressive or cancer chemotherapy. Bortezomib has been reported to induce viral reactivation(5.9% HBV reactivation rate)(Liu et al). Herein, we aim to present the rate and fate of HBV reactivation among myeloma patients who have received lenalidomide containing protocols.
Patients and Methods: We have evaluated 142 MM patients diagnosed between 2003-2014 who received lenalidomide during their treatment schedules whether for induction, relapse or post-induction maintenance treatment. 92 patients received 25 mg/day lenalidomide with Dexamethasone, 50 received at 10 mg/day as single agent. To be eligible for the analysis a minimum three months duration of treatment and no active hepatitis were required. Hepatitis B serology is rechecked before autologous peripheral stem cell transplantation and if liver enzyme abnormality occured. The hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (AntiHBe) are detected by Chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). HBV-DNA titers are determined by quantitative PCR.
Results: The median age of 142 MM patients was 56 (range, 42-77). 79 of patients were male (56%). ISS scores at diagnosis were as follows: ISS I/II/III: 51 (36%),57 (40%), 34 (24%). At the initiation of treatment 11 patients had negative HbsAg, positive AntiHBe, AntiHBcIgG, AntiHBs with normal liver function tests. Lamivudine prophylaxis was administered to these naturally immune 11 patients. One of these eleven patients and five patients who had no prior viral exposure had hepatitis B reactivation (4.2%) (Table). All these patients had hypogamaglobulinemia at diagnosis and had received bortezomib prior to lenalidomide. One patient had a history of dialysis. Four patients had received dexamethasone treatment in addition to lenalidomide. After treatment of tenofovir, HBV DNA titers decreased in all and disappeared among three of the six patients. Lenalidomide treatment was interrupted in three of the patients due to progression of disease. One patient who received a second stem cell transplantation for a secondary refractory disease had a progression to cirrhosis following high dose Melphalan.
Conclusion: In the current retrospective analysis we observed reactivation of hepatitis in 4.2% of patients who happened to have high ISS scores and were heavily treated previously. Only one patient had activation under prophylaxis. Lenalidomide can be associated with a low reactivation rate of HBV. Hepatitis B reactivation was detected more with lenalidomide and dexamethasone treated patients. The reactivation rate observed in this retrospective analysis is lower than those published previously and may account for the immune modulation effects of lenalidomide and close follow-up.
Table 1. Patient Characteristics (CR: Complete Response, PR: Partial Response, PD: Progressive Disease, VGPR: Very Good Partial Response) Patient Age (years)/MM type/ISS Treatment lines/Bortezomib prior/Lamivudine prophylaxis Hepatitis B markers at diagnosis Hepatitis B markers after revlimid treatment Treatment/Time to reactivation after lenalidomide (months) OS (months)/Status of disease 56/Lambda/2 3/+/- HBsAg-, HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg, AntiHBc+,AntiHBS- Tenofovir/11 20/CR 74/ IgGkappa/2 4/+/- HBsAg-,HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/18 52/PR 45 /IgGkappa/3 4/+/- HBsAg-HBeAg-AntiHBeAg-AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBs- Tenofovir/16 58/VGPR 61/ IgGkappa/3 5/+/- HBsAg-,HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/13 45/VGPR 43/IgAlambda/3 6/+/+ HBsAg-,HBeAg-AntiHBeAg+,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/7 58/PD 67/ IgGkappa/3 5/+/- HBsAg-HBeAg-AntiHBeAg-AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/12 66/PD

Disclosures
No relevant conflicts of interest to declare.