ABSTRACT
The COVID-19 pandemic has had global healthcare impacts, including high mortality from SARS-CoV-2 infection in cancer patients; individuals with multiple myeloma (MM) are es-pecially susceptible to poor outcomes. However, even for MM patients who avoided severe infection, the ramifications of the pandemic have been considerable. The consequences of necessary socio-geographical behavior adaptation, including prolonged shielding and inter-ruptions in delivery of non-pandemic medical services are yet to be fully understood. Using a real-world dataset of 323 consecutive newly diagnosed MM patients in England, we in-vestigated the impact of the COVID-19 pandemic on routes to myeloma diagnosis, disease stage at presentation and relevant clinical outcomes. We demonstrate increasing MM presentations via emergency services and increased rates of bony and extra-medullary dis-ease. Differences were seen in choice of induction therapy and the proportion of eligible patients undertaking autologous stem cell transplantation. Whilst survival was statistically inferior for emergency presentations, significant survival differences have yet to be demon-strated for the entire cohort diagnosed during the pandemic, making extended follow-up critical in this group. This dataset highlights wide-ranging issues facing MM patients conse-quent of the COVID-19 pandemic, with full impacts for clinicians and policy-makers yet to be elucidated.
Subject(s)
COVID-19 , Multiple Myeloma , NeoplasmsABSTRACT
Background: Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL) and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses.Method: We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with 2 different vaccine platforms.Results: Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n=204) or adenovirus-based (n=296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months-post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination.Interpretation: These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoral protection against the globally-dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.Funding Information: This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme.Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: Informed consent was obtained by remote consultation and work performed under the CIA UPH IRAS approval (REC 20\NW\0240) from North-West and Preston ethics committee and conducted according to the Declaration of Helsinki.