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2696 Safety and Tolerability of Sars-Cov-2 Vaccination and Natural History of Infection Among Patients with Castleman Disease

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma and Plasma cell Dyscrasias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Cytokine Release Syndrome, Clinical Research, Health Outcomes Research, Plasma Cell Disorders, Clinically Relevant, Patient-Reported Outcomes, Diseases, SARS-CoV-2/COVID-19, Infectious Diseases, Lymphoid Malignancies, Adverse Events
Sunday, December 12, 2021, 6:00 PM-8:00 PM

Sheila K Pierson, MSc1*, Russell Perkins2*, Frits van Rhee, MD PhD3, Corey Casper, MD, MPH4* and David C Fajgenbaum, MD, MBA, MSc2

1Center for Cytokine Storm Treatment & Laboratory, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
2Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
3Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR
4Infectious Disease Research Institute, Seattle, WA

Castleman Disease (CD) represents a group of rare and heterogeneous hematologic disorders that have common lymph node histopathology. Patients with CD are often immunosuppressed as a consequence of immunemodulating therapy or possibly due to an underlying immunologic dysfunction attributable to B-cell dysfunction. The most severe CD cases experience a cytokine storm disorder, a life-threatening exacerbation of circulating cytokines and immune-cell hyperactivation. Infection with SARS-CoV-2 progresses to a severe cytokine storm in the most severe cases of COVID-19. Interleukin-6 (IL-6) is central to the pathogenesis of CD, and increased IL-6 often accompanies severe COVID-19 cases; inhibition of IL-6 with monoclonal antibodies has been shown to be effective therapy for both CD and severe COVID-19. We therefore sought to understand the impact of COVID-19 infection on the natural history of CD and also examined the safety and tolerability of COVID-19 vaccines in this vulnerable patient population.

Patients enrolled in a longitudinal natural history study of CD (N=298) were invited to participate in a survey designed to characterize their experience with COVID-19 disease and vaccination. Surveys were emailed to all eligible patients, and reminders were sent up to 3 times. All data is self-reported; descriptive analyses are reported herein.

Of the 298 patients who received a survey, 101 (33.9%) completed it. Sixty-nine (68%) had been tested for SARS-CoV-2 at least once, and 10 (14.5%) reported testing positive – including 6 UCD, 3 iMCD, and 1 HHV8+ MCD patients. The reported prevalence of SARS-CoV-2 infection in the US compares at 10.5%. Two of the 10 patients reported asymptomatic disease (both UCD), 7 reported mild disease (4 UCD, 1 iMCD, 1 HHV8+MCD), and 1 reported moderate disease requiring hospitalization but not a ventilator or intensive care (iMCD). This severity distribution suggests that these potentially immunocompromised patients experience a range of disease severity consistent with SARS-CoV-2 infection in the broader US population. The most commonly-reported symptoms included fevers/chills, headaches, and loss of taste or smell (N=7 each), as well as shortness of breath/difficulty breathing, muscle and body aches, and cough (N=5 each). Rarer symptoms were also noted among the iMCD patients, including discoloration of skin, lips, or nailbeds (N=1) and newfound confusion (N=2). Two of the 10 patients reported stopping siltuximab treatment during their COVID-19 diagnosis; both subsequently resumed treatment. No other treatment changes were reported.

Of the 101 respondents, 87 (86%) had received at least 1 vaccine dose. Treatments, such as immunosuppressants and immunomodulators, were paused for 7 of these patients including, during the vaccination period; this was presumably done to increase the likelihood of a robust response to the vaccine. Fifty-one patients (59%) reported side effects to either dose 1 or 2. Side effects were generally mild, and none required hospitalization. Side effects were more commonly reported after dose 2, with the most common being arm pain (N=34), fatigue (N=30), and headache (N=26). Of those who reported not receiving the vaccine, 2 intend to receive it in the future, 5 reported being unsure about receiving it, and 7 do not intend to receive the vaccine. Common concerns include potential interaction with CD (N=9) and limited safety data (N=8).

This study represents the first investigation into the experience of CD patients with SARS-CoV-2 testing, diagnosis, and vaccination. We did not observe a markedly increased inflammatory response to SARS-CoV-2 infection, and vaccination was well-tolerated. A limitation is self-selection survey bias; it is possible that those who chose to participate represent those who had a milder reaction in general. However, it is noteworthy that there were no reports of severe disease in this sample. The prevalence of confirmed SARS-CoV-2 infection in this cohort (14.5%) is marginally higher than reported in the US population (10.5%) but statistical comparisons were not performed given that this study does not provide a general epidemiological estimate. However, the distribution of symptoms and vaccine adverse effects in this sample were comparable to the general population. Though additional follow-up is planned for the future, these data are an important basis for understanding the interaction of SARS-CoV-2 and CD.

Disclosures: Casper: EUSA Pharma: Consultancy. Fajgenbaum: Pfizer: Other: Study drug for clinical trial of sirolimus; N/A: Other: Holds pending provisional patents for 'Methods of treating idiopathic multicentric Castleman disease with JAK1/2 inhibition' and 'Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease'; EUSA Pharma: Research Funding.

OffLabel Disclosure: Our abstract makes reference to the following: "Interleukin-6 (IL-6) is central to the pathogenesis of CD, and increased IL-6 often accompanies severe COVID-19 cases; inhibition of IL-6 with monoclonal antibodies has been shown to be effective therapy for both CD and severe COVID-19." Inhibition of IL-6 with monoclonal antibodies for use in COVID-19 is off-label.

*signifies non-member of ASH