Razavi, Pedram

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701 .

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

Abstract Abstract 678 Background: Second primary malignancies (SPM) among multiple myeloma (MM) patients have been reported with an estimated incidence varying from 1%–15%. We have previously reported that significant disparity exists in MM survival across patients of different ethnicities. We undertook a Surveillance Epidemiology and End Results (SEER) based analysis to describe the incidence of SPM among MM patients of different ethnicities, in order to explore the variable impact that SPM might have on MM outcomes of patients across racial subgroups. Methods: SEER database was used to examine the standardized incidence rates (SIR) of SPM among MM patients diagnosed between 1973–2008. Observed to expected ratio (O/E) of SPM was calculated using incidence rates of cancers for the general population. The 95% confidence limits (CI) were constructed using Fisher's exact test. The analysis was restricted to patients with MM as first primary, microscopic confirmation of diagnosis, reporting sources not coded as autopsy- or death-certificate-only, and SPM reported more than 2 month after MM diagnosis. Mutually exclusive race/ethnicity categories were: African-Americans (AA), Asians/Pacific Islanders (API), Hispanic whites (HW), Non-Hispanic whites (NHW), and others. The risk of SPM among MM patients was explored by ethnicity, type of SPM, and latency period. Results: A total of 3090 cases of MM with SPM were diagnosed between 1973–2008, of which, 2021 patients met our inclusion criteria. Stratification of SPM by ethnicity revealed: 387 AA (19%), 72 API (4%), 51 HW (3%), 1500 NHW (74%) and 11 other (<1%) cases. There was an average 4.7-year latency period between diagnosis of MM and SPM (mean age 68.2 and 72.9 years, respectively). The latency period was not significantly different by type of SPM (solid organ vs. hematological) or ethnicity. AA had the youngest age at diagnosis for both, MM and SPM (65.6 and 70.1 year, respectively). (Figure 1) For all SPM sites analyzed together, there was no significant difference between the observed and expected incidence (O/E 0.98; 95% CI 0.94–1.02). However, O/E risk was significantly decreased for solid organ SPM (N=1695; O/E 0.92; 95% CI 0.88–0.96) and increased for hematological malignancies (N=263; O/E 1.63; 95% CI 1.44–1.84). Highest excess risk among all SPM was noted for acute non-lymphocytic leukemia (ANLL) (O/E 6.51; 95% CI 5.37–7.83). The overall risk of observed SPM was not different from expected rates by ethnicity, with the exception of HW who had a significantly decreased overall SPM risk. Table 1 summarizes significant results of O/E risk of SPM by race and site. HW and NHW were less likely to develop overall solid organ SPM. Within solid organ sites, HW had a significantly decreased O/E risk of developing lung/bronchus and prostate SPM. NHW were the only ethnic subgroup with an increased O/E risk of developing melanoma of skin, while the O/E risk of developing SPM of kidney/renal pelvis was increased only among AA. The risk of ANLL as SPM was significantly increased among AA, API, and NHW, while risk of NHL as SPM was only increased among NHW. Conclusion: Exploring potential causes of outcome disparities is important for evaluating disease characteristics and optimal triaging of healthcare resources for specific patient populations. We have performed the largest population-based analysis for the risk of SPM in MM patients stratified by race/ethnicity. We found that the risk of developing SPM among MM patients is variable depending on the patient's ethnic background. This warrants further exploration of the impact of SPM on outcomes of MM patients across different racial subgroups. Disclosures: No relevant conflicts of interest to declare.

SummaryStudies of ethnic disparities in malignancies have revealed variation in clinical outcomes. In multiple myeloma (MM), previous literature has focused only on patients of Caucasian and African‐American (AA) descent. We present a Surveillance Epidemiology and End Results (SEER)‐based outcome analysis of MM patients from a broader range of ethnicities, representing current United States demographics. The SEER 17 Registry data was utilized to analyse adult MM patients diagnosed since 1992 (n = 37 963), as patients of other ethnicities were not well represented prior to that. Overall survival (OS) and myeloma‐specific survival (MSS) were compared across different ethnicities stratified by year of diagnosis, registry identification, age, sex and marital‐status. Hispanics had the youngest median age at diagnosis (65 years) and Whites had the oldest (71 years) (P < 0·001). Increased age at diagnosis was an independent predictor of decreased OS and MSS. Asians had the best median OS (2·7 years) and MSS (4·1 years), while Hispanics had the worst median OS (2·4 years). These trends were more pronounced in patients ≥75 years. Cumulative survival benefit over successive years was largest among Whites (1·3 years) and smallest among Asians (0·5 years). These disparities may be secondary to multifactorial causes that need to be explored and should be considered for optimal triaging of healthcare resources.