Immunogenicity and Safety of the Recombinant Adjuvanted Herpes Zoster Vaccine in Patients with Chronic Lymphocytic Leukemia and Multiple Myeloma
Authors: Kontandreopoulou Christina-Nefeli , Stafylidis Christos , Labropoulou Vassiliki , Smilakou Stavroula , Vlachopoulou Dimitra , Patsialos Iraklis , Syriopoulou Stavroula , Gkikas Alexandros , Athanasopoulos Eleftherios N. , Vogiatzakis Anastasios , Panousi Eleni , Kyriakakis Georgios , Anastasopoulou Amalia , Mantzourani Marina , Diamantopoulos Panagiotis T 
Published: December 2024

Introduction
Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are profoundly immunocompromised and vulnerable of bacterial and viral infections, while their serologic response to several vaccines is lower than that of the general population. They are at risk for developing herpes zoster and are usually under prophylactic administration of antivirals for varicella-zoster virus (VZV) for long periods. The recombinant adjuvanted herpes zoster vaccine (Shingrix®; HZ/su, GlaxoSmithKline Biologicals SA) has been approved for immunocompetent and immunocompromised patients, but data on its efficacy in patients with CLL and MM are scarce. In the present study, we assessed the immunogenicity and safety of the Shingrix® vaccine in those patients.
Methods
Adult patients with CLL and MM from two University Hospitals, willing to be vaccinated with the Shingrix® vaccine, participated in the study after providing signed informed consent. The baseline disease and treatment characteristics of the patients were recorded. Patients were vaccinated with two 50 mcg doses of the vaccine administered intramuscularly at least one month apart. Seropositivity by IgM and IgG anti-VZV antibodies using the LIAISON® VZV assay panel (DiaSorin, Saluggia, Italy) was assessed before the first and after the second dose. IgG levels over 150 mIU/mL were considered positive. Patients were also followed for local or systematic adverse events (AEs), as well as for breakthrough infections. Statistical analysis was performed using the IBM SPSS statistics v23.
Results
Eighty-one patients with CLL (N=51) or MM (N=30) received at least one dose of the vaccine; 78 of them received both doses with a median of 32 (range 30-50) days apart, and 71 of them (CLL, 45; MM, 26) had a post-vaccination sample taken. The median age of the patients was 74 years. The IgM antibody levels both pre- and post-vaccination were below the seropositivity threshold in all patients. The median pre-vaccination IgG antibody level was 937.8 mIU/mL, with CLL patients having higher pre-vaccination levels than MM patients (1205.5 vs 466.7 mIU/mL, p=0.001). Although most patients were IgG-seropositive before vaccination (CLL, 96.0%; MM, 86.2%), there was a large increase in the IgG antibody level post-vaccination that was more pronounced in MM patients [median post-vaccination IgG level in CLL, 2079.5 mIU/mL (p=0.0005) and in MM, 2897.0 mIU/mL (p&lt;0.0001)]. The pre- and post-vaccination IgG levels were not associated with the baseline characteristics. In CLL patients the pre-vaccination levels were lower in actively treated patients (p=0.002) with no association with previous treatments. Nevertheless, the post-vaccination levels were high irrespective of active treatment in CLL patients. Finally, IgG levels were not associated with a prior history of herpes zoster, concurrent administration of antiviral prophylaxis, or any of the baseline complete blood count parameters or gamma-globulin levels, except that patients with a lower platelet count had lower antibody level (p=0.03). In MM patients both the pre- and post-vaccination levels were lower in patients with concurrent to the vaccination antiviral prophylaxis (p=0.031, p=0.013 respectively). A history of herpes zoster was present in 21% of the patients. One CLL patient with a prior history of herpes zoster had a new herpes zoster episode two months after the second vaccine dose. No other herpes zoster episodes were noted.
Adverse events (AEs) were reported by 56.9% of CLL and 50.0% of MM patients (p=0.065) after the first dose and by 54.0% and 39.3% after the second dose respectively (p=0.156). Most (75.0%) of the AEs were local (pain, edema, redness), while the systematic ones were low-grade except for one case of immune thrombocytopenia possibly attributed to the vaccine, which had to be treated with corticosteroids. There was no association of the emergence of AEs with the baseline characteristics of or the immunogenicity of the vaccine.
Discussion
The results of the present study show that patients with CLL and MM have adequate IgG antibody levels against VZV even before their vaccination but the antibody levels significantly increase in the vast majority of the patients after two doses of the vaccine. Actively treated CLL patients have lower antibody titles but both CLL and MM patients increase their title even when actively treated. AEs were mostly local or low-grade systematic ones.