Evaluation of SARS-CoV-2 Serological Testing in Patients with Multiple Myeloma and Other Hematologic Malignancies on Monoclonal Antibody Therapies

Abstract

Background: Patients with hematological malignancies (HM), including multiple myeloma (MM), frequently suffer from immune deficiency-associated infectious complications because of both the disease and the treatment. Alarming results from China and the UK confirm the vulnerability of HM patients to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven coronavirus disease 2019 (COVID-19). Given that the immunoassay interference from the endogenous monoclonal immunoglobulin (M paraprotein) and treatment antibodies continually challenges the MM management, it is critical to evaluate the SARS-CoV-2 serology tests for suspected interference/cross-reactivity.

Methods: We compared the degree of interference in three SARS-CoV-2 serology assay platforms in HM patients with and without COVID-19 and on various therapeutic monoclonal antibody (t-mAb) treatments. Further, we confirmed the cross-reactivity in pooled samples from normal and COVID-19 + samples spiked with respective antibodies in vitro.

Results: None of the 93 HM patient samples with or without t-MAbs showed cross-reactivity on any of the three serology platforms tested.

Conclusions: The tested three serologic assays for SARS-CoV-2 are specific and do not have cross-reactivity with M-components or t-MAbs indicating that they can be used safely in oncology practice and in research exploring the immunologic response to COVID-19 in patients with HM.

Keywords: COVID-19; M-spike; SARS-CoV-2; cross-reactivity; hematological malignancy; multiple myeloma; serology; therapeutic monoclonal antibodies.

Figure 1

(a) Flowchart of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology cross-reactivity testing study cases. Hundred and one unique hematological malignancy (HM) patient samples were included in SARS-CoV-2 serology testing. Eight of those were coronavirus disease 2019 (COVID-19)-positive by PCR, 30 were multiple myeloma (MM) patients and the remaining HM patients were on therapeutic monoclonal antibody (t-mAb) treatments. (b) Flowchart to assess the degree of interference in three SARS-CoV-2 serology assays due to different therapeutic monoclonal antibodies in normal and COVID-19 + samples by supplementing/spiking with respective antibodies in vitro. Pooled samples from normal and COVID-19 + patients were spiked with the clinically relevant concentration of each of the four therapeutic monoclonal antibodies—DARA (0.5 g/L), Ritu (0.5 g/L), Obin (0.5 g/L) and Bren (0.15 g/L)—or equal volume of saline for controls. These specimens then underwent analysis for the respective COVID-19 serology assays. Three pooled samples were used in each group (n = 3).