ABSTRACT
Introduction: Patients with hematologic malignancies, including multiple myeloma (MM), experience worse SARS-CoV-2 infection outcomes and sub-optimal vaccine responses. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precede MM and affect ∼5% of individuals age >=50. We previously showed that individuals with MGUS and SMM exhibit immune dysregulation. Here, we investigate the immune response to SARS-CoV-2 vaccination in these asymptomatic but potentially immunocompromised individuals. Methods: The IMPACT study (IRB #20-332) is a prospective study at Dana-Farber Cancer Institute in collaboration with MMRF, which enrolled individuals nationwide with a diagnosed plasma cell dyscrasia and healthy individuals. As of October 2021, 3,005 individuals completed a questionnaire regarding prior infection or vaccination. We obtained 1,350 blood samples from 628 participants and analyzed anti-SARS-CoV-2 IgG antibody titer by ELISA. Results: 2,771 (92%) participants were fully vaccinated (2 doses BNT162b2 or mRNA-1273;1 dose Ad26.COV2.s), 269 (9%) had received a 3rd mRNA vaccine dose, and 234 (8%) were unvaccinated. 1,387 (46%) and 1,093 (36%) participants received mRNA vaccines (BNT162b2 and mRNA-1273), and 139 (5%) participants received an adenovirus vector vaccine (Ad26.COV2.S). 34 (1%) individuals reported SARS-CoV-2 infection after full vaccination. We measured antibody titers in 201 MGUS, 223 SMM, 40 smoldering Waldenstrom macroglobulinemia (SWM), 64 MM, and 100 healthy controls. Multiple linear regression model estimated the association between various clinical variables and post-vaccination antibody titers. As previously reported, having MM was associated with low antibody titer (p < 0.001). Of note, having SMM, regardless of risk stratification by 2/20/20 criteria, was also associated with low antibody titers, indicating that even low-risk SMM patients have a poor response to vaccination. MGUS and SWM diagnoses were not significantly associated with antibody titers. Additionally, male sex (p < 0.010), elapsed time after vaccination (p < 0.001), and BNT162b2 vaccine (p < 0.001) were associated with low antibody titers. SARS-CoV-2 infection prior to vaccination was associated with high antibody titers. We identified 25 patients (6 MGUS, 10 SMM, 2 SWM, 7 MM) who submitted blood samples after both the 2nd and 3rd dose. In these patients we observed a significant increase in antibody titer after a 3rd dose (p = 0.002). We also observed that antibody titers of patients after a 3rd dose (13 MGUS, 12 SMM, 2 SWM, 31 MM) were comparable to that of healthy individuals after a 2nd dose (p = 0.833). Conclusion: Our data indicates that suboptimal response to SARS-CoV-2 does not only occur with MM and cancer patients receiving therapy but also in precursor asymptomatic patients including low-risk SMM.
ABSTRACT
Background and Aims: Cancers are known to worsen the clinical course of SARS-CoV-2 infection. We aimed to assess health outcome effectors in Coronavirus 19 (COVID-19) cancer patients from different centers in the US. Methods: We retrospectively evaluated medical records of 364 COVID-19 cancer patients from 3 centers in the US (New York, Michigan, and DC) admitted to the hospital between Dec. 2019 to Oct. 2021. Outcomes, symptoms, labs, and comorbidities of cancer patients with COVID 19 (Cases), were analyzed and compared with non-cancer COVID-19 patients (Controls). Results: Among 1934 hospitalized COVID-19 patients, 18.7% (n=364) have an active or previous history of cancer. Cancer patients were older when compared with non-cancer controls (69.7 vs 61.3 years). Among these 364 cancer patients, 222 were African Americans (61.7%) and 121 were Caucasians (33.2%). Cancer patients had an increased length of hospitalization compared to controls (8.24 vs. 6.7 days). The most common types of cancer in cases are prostate cancer (41.5%) and hematological malignancies (10.1%) among males, and breast cancer (41.5%), and head and neck cancers (11.4%) in females. In both genders, lung cancer is associated with high mortality. Patients with a previous history of cancer were more prone to death (p=0.04) than active cancer patients. Cough (23.1%) and fever (19.5%) are the most common symptoms among the cases. In univariate and multivariate analyses, predictors of death among cancer patients were male sex, older age, African American ethnicity/race, asthma, presence or absence of fever, elevated troponin, mechanical ventilation, and previous history of cancer. There is no significant difference in mortality in cancer patients when compared to controls. Abdominal pain (2.2%), diarrhea (3.8%), and vomiting (2%) occurred both in cases and controls but did not associate with death. Albumin is also significantly associated with mortality in cases (p=0.042). AST (54.6%), ALT (12.5%), and Bilirubin (16%) were elevated in the majority of cases. Both AST and ALT alterations have an effect on mortality. Univariate analysis shows that AST is strongly and significantly associated with mortality in cases (p=0.001) but not in controls. ALT is also associated with mortality in cases at the 10% level (p=0.057). Diarrhea is strongly associated with mortality in control (p <0.001) but not in cases. Conclusion: In this retrospective cohort study, we found male sex, and African American race is associated with high mortality. Elevated troponin levels and LFT’s during the hospital stay were significantly associated with poor outcomes. Patients with a previous history of cancer were more prone to death when compared to active cancer COVID-19 patients. Early recognition of cancer COVID-19 patients can help determine appropriate treatment and management plans for better prognosis and outcome.