Low Risk of Reactivation of Hepatitis B and Hepatic Injury in Multiple Myeloma (MM) Patients (pts) Undergoing Autologous Stem Cell Transplant (ASCT).

The risk of viral reactivation in hepatitis B carriers (hepatitis B surface antigen positive; HBsAg+) undergoing chemotherapy for lymphoma is well-recognized (up to 60%) with liver-related mortality of over 5%. Even in pts who clear the HBsAg and develop antibodies (HBsAbs and/or HBcAbs), the risk of reverse seroconversion is high. Immunodeficiency due to the underlying lymphoma or to therapy (in particular, steroids, rituximab) and the periodic nature of lymphoma chemotherapy which allows for viral replication, all appear to contribute to this high risk. As a result, it is standard practice to use antiviral prophylaxis in lymphoma pts previously exposed to hepatitis B (HBcAb+) undergoing immunosuppressive therapy. Unlike in lymphoma, the risk of viral reactivation and liver injury during treatment for multiple myeloma is not as well-described, although use of high-dose steroids is common and severe immunosuppression occurs with therapies such as ASCT. Routine antiviral prophylaxis during therapy for HBcAb+ MM pts, who are not carriers (HbsAg negative), is therefore not standard practice. In this review, we aimed to identify the incidence of hepatitis B exposure and seropositivity in a population of MM pts undergoing ASCT and determine the risks of viral reactivation and hepatic injury during the peri-transplant period.

All MM pts undergoing ASCT at our centre from May 2004 to Dec 2008 were included in this review. At our institution, pts undergoing stem cell mobilization are routinely screened for hepatitis B serology (HBsAg, HBcAb, HBsAb). Patient demographics, MM and treatment details, and peri-transplant toxicities (including liver enzyme elevations) from onset of induction therapy to 6 mos post-transplant were collected by retrospective chart and database review. All pts during this period received 4-6 cycles of high-dose dexamethasone-based induction therapy, stem cell mobilization with cyclophosphamide 2.5g/m² and GCSF 10ug/kg/day, and transplant conditioning with melphalan 200mg/m².

A total of 475 MM pts were reviewed, of which 51 (10.7%) were HBcAb+ indicating prior viral exposure. Of these 51 pts, 7 were hepatitis B carriers with persistent HBsAg+ (carrier rate 1.4%).

Amongst the 51 pts with prior viral exposure (HBcAb+), ethnicities include: Asian 35%, Caucasian 33%, African-Canadian 18%, Hispanic 14%. Median age was 56 yrs (range 37-72), 32% male. The median time from MM diagnosis to ASCT was 9.2 mos (range 4.7-29.4). MM subtypes - IgG (51%), IgA (18%), light chain (31%). Of the 44 HBcAb+ pts who were not carriers (HBsAg negative), 10 pts (22.7%) had not developed immunity and lacked HBsAbs in the serum.

Although routine antiviral prophylaxis was not used at our institution, 12 pts received lamivudine at some time during the peri-transplant course. Of the 51 HBcAb+ pts, 14 (27.4%) developed liver enzyme elevations (≥2-fold upper limit normal) during the peri-transplant period; no different from the 424 pts without hepatitis B exposure (23.8%, p=0.73). Only 3 pts (5.8%) developed reactivation hepatitis (2 during induction, 1 post-transplant 5 mos) confirmed by increases in serum HBV DNA levels. Two of these pts were HBsAg+ carriers; 1 pt was HbsAg negative but positive for HBV DNA (reverse seroconverter). Therefore, 2 of 7 (29%) hepatitis B carriers developed reactivation hepatitis vs one of 44 (2.2%) pts with HBcAb+ only. No liver-related deaths were seen.

The median follow-up for all 475 patients from diagnosis is 34.2 mos (range 3.5-21.3). Interestingly, the 5-year probability of survival from diagnosis is shorter for the HBcAb+ pts than for the 424 pts without prior viral exposure (0.58 versus 0.82; p=0.05). Liver-related deaths associated with subsequent relapse therapies may be implicated.

1. The incidence of prior hepatitis B exposure (HBcAb+) in MM pts undergoing transplant in our ethnically diverse population is 10.7%.

2. Without routine antiviral prophylaxis, the rate of viral reactivation and liver injury during the peri-transplant period is low (5.8%).

3. Hepatitis B carriers (HbsAg+) were less common (1.4%) but were at particularly high risk, with a reactivation hepatitis rate of 29%.

4. Routine prophylaxis for all hepatitis B exposed pts may not be warranted but is strongly encouraged for hepatitis B carriers.

5. The risk of hepatitis B reactivation and hepatic injury in the setting of novel agents and aggressive combination therapies requires further evaluation.

No relevant conflicts of interest to declare.