Kinetics of anti‐SARS‐CoV‐2 neutralizing antibodies development after BNT162b2 vaccination in patients with amyloidosis and the impact of therapy

Abstract

and Ian W. Flinn contributed to the collection and assembly of data, and data analysis/interpretation; Annalisa Chiappella and Franck Morschhauser contributed to data analysis and interpretation; Tycel Phillips, Andy I. Chen, James Essell, Annalisa Chiappella, and Catherine Diefenbach contributed to the treatment of study patients; Ji Cheng contributed to the statistical analysis and interpretation of the clinical data. DATA AVAILABILITY STATEMENT Qualified researchers may request access to individual patient level data through the clinical study data request platform (https://vivli.org/). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: (https://www.roche. com/research_and_development/who_we_are_how_we_work/clinical_ trials/our_commitment_to_data_sharing.htm).

SARS-CoV-2 Neutralizing Antibodies Kinetics Postvaccination in Cancer Patients under Treatment with Immune Checkpoint Inhibition

“…Indeed, after the third dose no patients and controls were seronegative. These findings are consistent with previously published research on the antibody kinetics in cancer patients after a period of a few months following full vaccination [ 25 , 26 , 27 , 28 , 29 , 30 ]. Furthermore, a recently published meta-analysis demonstrated reduced seroconversion rates after one COVID-19 vaccine dose in patients with solid cancers (Risk Ratio: 0.55; 95% confidence interval: 0.46–0.65; I2 = 78%; Absolute Risk: 0.44; 95% CI: 0.36–0.53; I2 = 84%) in comparison with immunocompetent controls; yet, the administration of a second dose led to significantly increased seroconversion (Risk Ratio: 0.90; 95% CI: 0.88–0.93; I2 = 51%; Absolute Risk: 0.89; 95% CI: 0.86–0.91; I2 = 49%), whereas the 3rd dose was associated with enhanced humoral response in vaccine non-responders with solid tumors, further highlighting the benefits of a booster dose [ 31 ].…”

Seroconversion Rates After the Second COVID-19 Vaccination in Patients With Systemic Light Chain (AL) amyloidosis

“…7,10 Among the patients who were on active treatment or had received treatment with daratumumab within 3 months before vaccination (n = 28), we observed a relevant proportion of patients with high (n = 6) or at least detectable (n = 18) anti-SARS-CoV-2-S1 antibody levels (Figure 1B). Similar to others, 13 our study did not show that the use of daratumumab significantly impairs the antibody response compared with other active treatments in amyloidosis. Considering that only 7% of the AL amyloidosis patients in this study were diagnosed with an underlying multiple myeloma, the immunosuppressive effect conferred by the smaller underlying plasma cell clone might be less stronger than in multiple myeloma treated with daratumumab.…”

“…With a median antibody level of 36.6 among the seroconverted patients, the antibody level was remarkably lower than the level, which was reported in a large healthy vaccinated cohort using the same analysis pipeline (median reported antibody level in healthy cohort: 116.2) 12 . The observation of inferior antibody levels in patients with AL amyloidosis is quite similar to reported low‐antibody levels in patients with multiple myeloma 7 and underscores the immunosuppressive effect of the underlying plasma cell clone and the administered antiplasma cell treatments in AL amyloidosis 11,13 …”

“…12 The observation of inferior antibody levels in patients with AL amyloidosis is quite similar to reported low-antibody levels in patients with multiple myeloma 7 and underscores the immunosuppressive effect of the underlying plasma cell clone and the administered antiplasma cell treatments in AL amyloidosis. 11,13…”

“…12 The observation of inferior antibody levels in patients with AL amyloidosis is quite similar to reported low-antibody levels in patients with multiple myeloma 7 and underscores the immunosuppressive effect of the underlying plasma cell clone and the administered antiplasma cell treatments in AL amyloidosis. 11,13 The majority of patients in this study (96%) were on active treatment or had received treatment before vaccination, which allowed us to further explore the impact of timing and type of treatment on anti-SARS-CoV-2-S1 antibody responses. Based on the large spectrum of antibody levels, we divided patients in 3 groups, which included high responders (anti-SARS-CoV-2-S1 ≥100), low responders (anti-SARS-CoV-2-S1 ≥1 and <100), and nonresponders (anti-SARS-CoV-2-S1 <1).…”