COVID-19 AND MYELOMA
Authors: H Ludwig, P Sonneveld, M Boccadoro, E Terpos
Journal: HemaSphere (2022)

The disease- and treatment-induced immunosuppression in MM accounts for a two-fold higher risk for infection with the SARS-CoV-2 virus, an increased risk for a prolonged, severe symptomatic disease, and an increased mortality. Most pts are aware of these risks and show a higher compliance with vaccination recommendations compared to the general population. Several studies revealed differences in the humoral and cellular immune response between pts with MGUS, SMM, and MM, with normal median antibody titers in MGUS, moderately impaired response in SMM, and significantly reduced antibody response in MM, albeit with a wide variation in titers between individual pts. Pts with active, poorly controlled disease and those exposed to CD38 and BCMA-targeting treatments frequently show no or reduced SARS-CoV-2 antibody responses. The EMN issued a consensus that MM pts should ideally be vaccinated before onset of active disease and/or during periods of well controlled disease. A third dose should be administered after an interval of approximately 6 months, and early data in immunocompromised pts show a vaccination response in several previously poorly responding pts after a forth dose. An open question pertains to the role of the interrelationship between the innate, humoral and cellular immune system. Neutralizing antibodies provide the best proxy for protection, although specific thresholds associated with protection against infection are unlikely to be established given the many factors associated with infection control. Antibody titers decline with time from vaccination and more so in vaccinated pts compared to those who have been infected and vaccinated, mandating booster shots in time intervals that need to be established. Pts may present without measurable antibody titers but with detectable cellular immunity or vice versa, although in most reports, correlations between antibody and cellular response were noted. Data suggest that SARS-CoV-2 specific memory B and T cells persist for prolonged periods. One of the threads to patient protection is the substantial mutational activity of the SARS-CoV-2 virus with reduced neutralizing capacity of vaccine induced antibodies against recent variants of concern, particularly the omicron variant, posing vaccinated pts at risk for breakthrough infections. Recent research efforts resulted in new prophylactic treatments for pts with high risk for severe COVID-19 disease (Table 1) that have been shown to reduce the incidence of severe complications. Table 1. - Recently approved drugs with activity against the omicron variant for post exposure prophylaxis in pts with high risk for severe COVID-19 disease Medicine Mode of Action Administration EMA/FDA approved Nirmatrelvir and Ritonavir (Paxlovid) Antiviral 2 tablets Nirmatrelvir plus 1 tablet Ritonavir twice daily for 5 days Yes/EUA Molnupiravir (Lagevrio) Antiviral 4 tablets twice daily for 5 days EUA*/EUA Remdesivir (Veklury) 200 mg IV infused over 30-120 min, then day 2 and thereafter: 100 mg i.v. q/day for 5 days (10 days max) Yes/Yes Sotrovimab (Xevudy) Monoclonal antibodies 500mg through an infusion over 30 minutes Yes/EUA Tixagevimab co-packaged with Cilgavimab (Evusheld**) Monoclonal antibody cocktail 300mg of Tixagevimab and 300mg of Cilgavimab administered in 2 separate consecutive i.m. injections Submitted/EUA Bebtelovimab Monoclonal antibody 175mg through an infusion over 30 minutes No/EUA *EUA: Emergence use authorization,**approved for pre-exposure prophylaxis also, extended half-life, repeat administration in 6 months