Spike antibody seroconversion and breadth following SARS-CoV-2 vaccination in Australian people with multiple sclerosis

Background: COVID-19 vaccination induces protective Spike antibodies. Some responses are attenuated in people with multiple sclerosis (MS) on high efficacy disease-modifying therapies (DMT).Whether antibodies afford immunity against emerging SARS-CoV-2 Variants of Concern (VoC) such as Delta and Omicron is unknown. Aim(s): To assess the longevity and breadth of Spike antibody in MS patients after COVID-19 vaccination. Objective(s): To determine seroconversion and antibody binding toVoC Spike. Method(s): Spike antibodies to Clade A SARS-CoV-2 were assessed in 535 MS sera at baseline (n=292), 1 (n=141) and 6 month (n=67) post-second dose, and 1 month post-third dose (n=35), and 489 health worker controls. When known, COVID- 19 vaccines were BNT162b2 (n= 489 controls, n=108 MS patients) and ChAdOx1-S (n=37).Spike antibody binding to VoC Delta and Omicron BA1 was assessed in 68 sera 1 month post-second dose. Demographic and DMT information was available in 269 patients. Result(s): 123/141 sera at 1 month post-second dose, 66/67 at 6 months post-second dose, and 26/35 at 1 month post-third dose were positive for Spike antibodies.Patients who did not seroconvert at 1 and 6 month post-second and 1 month post-third dose (n=28) were treated with ocrelizumab (n=22), cladribine (n=1), fingolimod (n=4), and siponimod (n=1). At 1 month post-second dose, the median and IQR Spike antibody levels were 67,224+/- 101,251 in the seroconverted MS group compared to 145,510+/- 99,669 in controls (n=489). When patient sera were assessed for binding to Clade A Spike, and VoC Delta and Omicron BA1 Spikes, most sera were able to bind the three different Spike antigens (n=61). However, Spike antibody immunoreactivity was decreased by 70% against Delta Spike and 90% for Omicron BA1 Spike compared to the original clade A Spike.As observed for Clade A Spike antibody, DMTs, such as ocrelizumab, fingolimod, and ofatumumab, decreased the antibody binding to Delta and Omicron Spike. Still, the pattern of antibody recognition was similar between the three Spikes and all DMTs analysed, i.e. alemtuzumab, natalizumab, teriflunomide, and interferons. Our data suggest that, irrespectively of DMTs, antibodies generated after vaccination did not bind Spike from recent VoCs to the same extent as the original Spike used in COVID-19 vaccines. Conclusion(s): Some DMTs reduce Spike antibody titres or prevent seroconversion. The sequence of Spike used in the first generation of vaccines may need to be updated for emerging VoC.

A multicenter real-world study reviewing systemic anticancer treatment choices and drop off rates between treatment lines for metastatic renal cell carcinoma in the United Kingdom: In the immunotherapy era

Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved over the last few years with several systemic anti-cancer therapies (SACT) licensed across different lines of treatment. A previous real world study in the UK had demonstrated a significant attrition rate between each line of therapy suggesting less than half of patients who received first line SACT then received second line therapy and less than a fifth of first line SACT patients reach third line. Methods: We conducted a retrospective analysis of all patients treated between January 2018 and end of June 2021 to see if advancement in treatment options had impacted on the drop-off rates. Data was collected from 5 UK sites. Patients were identified from electronic SACT database. All reimbursed treatment options including the COVID interim treatment guidelines options were included. Patients who received SACT as part of a clinical trial were also included. Patients who remained on the respective lines of treatment were censored. Results: Data for 515 patients (372 male: 143 female) who received first-line SACT for mRCC were included in the analyses. IMDC prognostic groups were 103 favourable, 236 intermediate, 127 poor (49 not available). On progression 69% of patients were able to receive second-line therapy and 34% were able to receive third-line therapy. Of the 515 first-line therapies, 24% of patients received frontline ipilimumab and nivolumab, 10% received TKI and IO combination and 63% received single agent VEGF TKI. Second-line nivolumab or cabozantinib (43% and 40% respectively) were the most commonly prescribed options. Third-line cabozantinib 61% and nivolumab 16% remain the most used options. Across all lines of therapy progressive disease was the primary reason for discontinuation. 5% switched treatment due to toxicity. Conclusions: These results suggest that, with more treatment options available, including combination/ immunotherapy therapies, more patients are able to receive second and third-line therapies. Despite this, nearly one third of patients only receive one line of treatment which highlights the need to deliver the most efficacious treatments first to optimise patient outcomes. Moreover, single agent TKI was the most commonly used first-line SACT despite advances in the management pathway. Data analysing the impact of COVID on treatment selection will be presented.

Germline BRCA1/2 mutation testing in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC): A real-world study in the Syapse Learning Health Network (LHN)

Background: Germline (g)BRCA1/2 mutations represent approximately 5% of metastatic breast cancer. Poly ADP-ribose polymerase inhibitors (PARPi) have shown improved clinical outcomes, a manageable toxicity profile, and favorable patient (pt)-reported outcomes versus chemotherapy in pts with gBRCA1/2 mutated HER2-locally advanced or metastatic breast cancer. With the advent of PARPi, clinical guidelines have broadened eligibility criteria for gBRCA1/2 testing. However, limited information is available on the impact of the COVID-19 pandemic on gBRCA1/2 testing rates. We assessed trends and factors associated with gBRCA1/2 testing in pts with HER2-ABC before and during the COVID-19 pandemic. Methods: This retrospective study included pts from the Syapse LHN, a longitudinal database of pts with cancer cared for in community-based, integrated care delivery networks in 25 states in the United States. Pts were eligible for gBRCA1/2 testing from initial ABC diagnosis until death or date of last contact with the participating health system. Information on gBRCA1/2 testing was obtained from scaled sources and further curated by Certified Tumor Registrars. Logistic regression evaluated the associations between age at diagnosis, family Shistory of relevant cancer, race/ethnicity, median household income, health system, and diagnosis year with gBRCA1/2 testing among HER2-ABCs;models included hormone receptor status. Results: The study population included 1769 pts with HER2-ABC, including 577 pts with triple negative ABC initially diagnosed from 2010: 96% were women, 69% were non-Hispanic White, and 94% had an estimated median household income >$30, 000 USD;median age at initial diagnosis was 61 years. The percentage of pts ever gBRCA1/2-tested among those eligible increased over time: 26%, 28%, and 31% by end of 2018, 2019, and 2020, respectively. Similarly, the percentages of new testing among eligible but not previously tested pts increased from 2018-March 2020, decreased from April-September 2020, and trended upwards thereafter (Table 1). In logistic regression models combining data from pre-and post-COVID-19 periods, family history of relevant cancer (odds ratio [OR]=1.9;95% CI, 1.5-2.4), younger age at diagnosis (>65 reference;<45: OR=12.8, 95% CI, 8.9-18.3;45-54: OR=6.7, 95% CI, 4.9-9.3;55-64: OR=2.0, 95% CI, 1.5-2.8), and diagnosis year of 2013 or later (OR=1.9, 95% CI, 1.4-2.6) were significantly associated with increased odds of gBRCA1/2 testing. Positive hormone receptor status (OR=0.5;95% CI, 0.4-0.6) and Hispanic ethnicity (OR=0.5;95% CI, 0.3-0.9) were significantly associated with reduced odds;associations with non-Hispanic Black ethnicity did not reach statistical significance (OR=0.8;95% CI, 0.6-1.1). Conclusion: Following the expanded eligibility criteria for gBRCA1/2 testing, testing rates increased from 2018 to 2019 and decreased only slightly during the national COVID-19 lockdown. Age at diagnosis, family history, diagnosis year, ethnicity, and hormone receptor status impacted the odds of testing. Given that gBRCA1/2 mutations are actionable, focused efforts should be developed to resume the pre-pandemic trajectory of gBRCA1/2 mutation testing.

HOSPITAL @HOME: TREATING SEVERE COVID-19 IN THE COMMUNITY

Introduction Patient numbers during the second wave of COVID-19 threatened to overwhelm hospital capacity. Hospital @home services bring the ward to the patient;providing acute care in the home, delivered by a specialised multi-disciplinary team. Our Hospital @home was ideally placed to adapt to support the care of COVID patients in the community who would otherwise have required hospitalisation yet were unlikely to benefit from level 2/3 care. Here we report on the process and 30 day outcomes. Methods An evidence-based guideline for the treatment of severe COVID by Hospital @home was developed. A severe bundle pack including dexamethasone, oxygen, IV fluids and thromboprophylaxis was used at first patient contact. Patients were referred from the community or from hospital and streamed into severe or non-severe pathways. Outcome data was retrospectively extracted from the notes of all COVID positive patients admitted to hospital @home between 16/12/2020 and 14/02/2021. Results 125 COVID patients were treated by hospital @home. Patients were triaged by infection severity: severe (n = 42, 34%) and non-severe (n = 83, 66%). Average length of stay with hospital @home was 6.8 days (IQR 4–8);equivalent to 855 occupied bed days—i.e. one 28 bed ward for 30.5 days. 33 patients were treated with the severe COVID bundle with an average Clinical Frailty Score 6.9 (IQR 6–8). 30 day outcomes for patients treated with the severe bundle were: 13 (39%) alive in the community (average CFS 6.2), 1 (3%) in hospital and 19 (57%) deceased (average CFS 7.4). Conclusion Rapid redesign of an existing hospital @home service during the COVID pandemic offered appropriate patients the choice to have Level 1 hospital care in their home. Hospital @home has an essential role in offering alternative pathways of care to patients and optimising local healthcare capacity.

Using real-world data (RWD) from anintegrated platform for rapid analysis of patients withcancer with and without COVID-19 across distinct healthsystems

Introduction: Reports suggest worsened outcomes in patients with cancer (pts) and COVID-19 (Cov), varying bygeography and local peak dynamics. We describe characteristics and clinical outcomes of pts with and without Cov. Methods: RWD at 2 Midwestern health systems from the Syapse Learning Health Network were used to identifyadults with active cancer (AC) or past history of cancer (PHC). AC pts were identified by encounters with ICD-10code for malignant neoplasm or receipt of an anticancer agent within 12 months prior to February 15, 2020;PHC pts were identified by encounters with an active cancer code from May 15, 2015 to February 15, 2019 and no receipt ofanticancer therapy within the prior 12 months. Cov was defined by diagnostic codes and laboratory results fromFebruary 15 to May 13, 2020. Comorbidities were assessed prior to February 15, 2020;hospitalizations (hosp), invasive mechanical ventilation (IMV), and all-cause mortality (M) were assessed from February 15 to May 27, 2020. Results: We identified 800 pts with Cov (0.5%) out of a total of 154,585 pts with AC or PHC. Compared to AC pts without Cov (AC WO, 39,402), AC pts with Cov (AC Cov, 388) were more likely to be non-Hispanic Black (NHB,39% vs. 9%), have renal failure (RF, 24% vs. 12%), cardiac arrhythmias (33% vs. 19%), congestive heart failure(CHF, 16% vs. 8%), obesity (19% vs. 14%), pulmonary circulation disorder (PCD, 9% vs. 4%), and a zip code withmedian annual household income (ZMI) <$30k (18% vs. 5%). Comorbidity and income were similarly distributed forPHC pts with Cov (PHC Cov, 412). Compared to PHC pts without Cov (PHC WO, 114,383), coagulopathy (coag)was more common in PHC Cov pts (10% vs. 5%). Hosp for AC Cov pts was higher than for AC WO pts (81% vs.15%). Hosp for PHC Cov pts was also higher than for PHC WO pts (68% vs. 6%). Hosp was highest for NHB pts inboth AC Cov and PHC Cov groups (88% and 72%) and for AC Cov pts in low ZMI (94% in <$30K). Pts <50 yearsold had hosp rates of 79% (AC Cov) and 49% (PHC Cov). IMV rate for AC Cov pts was higher than for PHC Cov pts(21% vs. 14%). Rates of IMV for AC Cov pts were highest in low ZMI (27%) and in pts with coag (36%). M by group was: AC Cov 16%;AC WO 1%;PHC Cov 11%;PHC WO 1%. Among AC Cov pts, M was higher for men (19% vs.13%) and pts with PCD (31%), RF (25%), or diabetes (DM, 24%);among PHC Cov pts, M was also higher for men(14% vs. 8%) and pts with coag (30%), valvular disease (27%), or PCD (24%). Increasing age, DM, RF, and PCD were associated with increased risk of M for AC Cov pts in age, race/ethnicity, and comorbidity-adjusted logisticregression;increasing age and coag were associated with M in PHC Cov pts. Conclusion: In this rapid characterization from RWD, pts with Cov have higher rates of pre-existingcardiopulmonary/vascular and renal conditions and increased risk of hospitalization, IMV, and mortality than pts without Cov. Higher Cov risk and worse outcomes in NHB and lower-income pts suggest health care disparities.Whether these outcomes are due to comorbidities or acute sequelae merits further study, as does investigation ofalternative definitions for real-world populations and outcomes.