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SESSION TITLE: Cases of Overdose, OTC, and Illegal Drug Critical Cases Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Anchoring bias is a cognitive bias where one relies too heavily on initial information early on in the decision making process, affecting subsequent decisions due to future arguments being discussed in relation to the "anchor. Overemphasis on COVID-19 due to the pandemic has impacted the timely diagnosis and treatment of other diseases. CASE PRESENTATION: A 39-year-old man with a past medical history of COVID 19 in 12/2020 presents to the ED with increasing weakness, chest pain, recurrent fevers, diarrhea, and cough. CXR revealed bilateral infiltrates suggestive of pneumonia/pulmonary edema. Patient was empirically started on ceftriaxone. CT chest was suspicious of COVID-19;however repeat testing was negative. Diarrhea did not improve. Patient later admitted to recent travel to Jamaica. Ova and parasite, C-difficile, and stool culture were negative. On hospital day 8, the patient was intubated and placed on mechanical ventilation for worsening hypoxic respiratory failure Infectious disease was consulted for recurrent fevers of unknown origin and diarrhea with recent travel. Testing for typhoid fever, hantavirus, malaria, HIV, zika virus, chikungunya, dengue, and yellow fever were performed. Consent was obtained for HIV testing. HIV antibody tests were positive, CD4 count of 7, and viral load greater than 900k. Since a new diagnosis of AIDS with a CD4 count of 7 was obtained, the patient was subsequently tested for opportunistic infections such as TB. TB sputum PCR testing was positive but AFB smear was negative for TB. Antiretroviral and tuberculosis treatments were initiated. DISCUSSION: Anchoring bias can delay critical diagnoses and impede patient care if it is not recognized. According to Watson et. al, one way physicians circumvent the thought of pretest probability when ordering tests based on patient history and the subsequent list of differential diagnoses is anchoring bias. Bypassing the pretest probability also alters the sensitivity and specificity of testing because results that do not confirm or rule out a top differential diagnosis are thought to be inaccurate and are then repeated attributing the initial result to a bad specimen or an improper collection of the specimen. CONCLUSIONS: The case presented exemplifies clearly the concept of anchoring bias. Upon initial presentation, the patient had nonspecific symptoms such as weakness, chest pain, recurrent fevers, diarrhea, and cough, all of which can be symptoms of COVID 19 in the setting of a global pandemic. It is clear that the initial diagnosis based on these symptoms was COVID 19. When initial testing was negative, anchoring bias still played a role in the decision to test the patient once again, despite the first negative test. Repeat testing still did not support the diagnosis of COVID 19, which expanded the differential diagnosis and ultimately led to the correct diagnosis of AIDS with concomitant TB infection. Reference #1: Saposnik, et. Al. Cognitive Biases Associated with Medical Decisions: A Systematic Review. BMC Med Inform Decis Mak. 2016 Nov. 3. PMID: 27809908 Reference #2: Harada, et. al. COVID Blindness: Delayed Diagnosis of Aseptic Meningitis in the COVID-19 Era. Eur J Case Rep Intern Med. 2020 Oct 23. PMID: 33194872. Reference #3: Singh, et. al. The Global Burden of Diagnostic Errors in Primary Care. BMJ Qual Saf. 2016 Aug 16. PMID: 27530239. DISCLOSURES: No relevant relationships by Sagar Bhula
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BACKGROUND Cellular therapies (allogeneic hematopoietic cell transplantation, allo-HCT, autologous hematopoietic cell transplantation, auto-HCT, and chimeric antigen receptor T cell therapy, CAR T) render patients severely immunocompromised for extended periods post-therapy. Emerging data suggest reduced immune responses to COVID-19 vaccines among patients with hematologic malignancies, but data for cellular therapy recipients are sparse. We therefore assessed immune responses to mRNA COVID-19 vaccines among patients who underwent cellular therapies at our center to identify predictors of response. PATIENT AND METHODS In this observational prospective study, anti-SARS-CoV-2 spike IgG antibody titers and circulating neutralizing antibodies were measured at 1 and 3 months after the 1 st dose of vaccination. CD4, CD19, mitogen, and IgG levels from patient samples collected prior to initiation of vaccination in a subset of patients were used to assess immune recovery and association with response. A concurrent healthy donor (HD) cohort provided control response rates. RESULTS Allo-HCT (N=149), auto HCT (N=61), and CAR T (N=7) patients vaccinated between 12/22/2020- 2/28/2021 with mRNA vaccines and 69 HD participated in this study. At 3 months, 188 pts (87%) had a positive anti-SARS-CoV-2 spike IgG levels (median 5,379 AU/mL, IQR 451-15,750), and 139 (77%) had a positive neutralization Ab assay (median 93%, IQR 36-96%). All HD (100%) had a positive anti-SARS-CoV-2 spike IgG and a positive neutralization Ab assay with median levels of 8,011 AU/mL (IQR 4573-11,159) and 96% (IQR 78- 96%), respectively. Time from vaccination to cellular therapy was associated with response;67% of patients vaccinated in the first 12 months post-cellular therapy (N=42) mounted a serologic response, compared with patients vaccinated between 12-24 (89%) (N=45), 24-36 (91%) (N=32) and >36 (93%) (N=98) months post-treatment, p= 0.001 (figure 1). Patients with immune parameters below the recommended threshold for vaccinations post-cellular therapies were also less likely to mount a response (figure 2): CD4+ T-cell count < 200 vs >200 cells/μL, 66% vs 87% (p=0.012);CD19+ B-cell count <50 vs >50 cells/μL;33% vs 95% (p<0.001), phytohemagglutinin mitogen response <40% vs >40%, 42% vs 89% (p<0.001), and IgG <500 vs >500 mg/dl, 71% vs 91% (p=0.003). Patient age, gender, prior COVID-19 infection, treatment with IVIG, and type of mRNA COVID-19 vaccine were not associated with the likelihood of serologic response. CONCLUSION This largest cohort to date, demonstrates that COVID-19 vaccine responses of cellular therapy recipients are reduced compared to healthy control and response varies based on time interval from cellular therapy and immune function at the time of vaccination, underscoring the importance of monitoring immune status parameters, as well as qualitative measures (neutralizing Ab) of vaccine response, in informing clinical decisions, including the indication for booster vaccines. [Formula presented] Disclosures: Politikos: Merck: Research Funding;ExcellThera, Inc: Other: Member of DSMB - Uncompensated. Vardhana: Immunai: Membership on an entity's Board of Directors or advisory committees. Perales: Equilium: Honoraria;Cidara: Honoraria;Sellas Life Sciences: Honoraria;Miltenyi Biotec: Honoraria, Other;Celgene: Honoraria;MorphoSys: Honoraria;Takeda: Honoraria;Incyte: Honoraria, Other;Karyopharm: Honoraria;Kite/Gilead: Honoraria, Other;Merck: Honoraria;NexImmune: Honoraria;Novartis: Honoraria, Other;Medigene: Honoraria;Omeros: Honoraria;Servier: Honoraria;Bristol-Myers Squibb: Honoraria;Nektar Therapeutics: Honoraria, Other. Shah: Amgen: Research Funding;Janssen Pharmaceutica: Research Funding.
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Introduction: The standard approach for relapsed or refractory (RR) classical Hodgkin lymphoma (cHL) following front-line treatment failure is second line therapy (SLT) aimed to achieve complete response (CR), followed by consolidation with high dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). No one standard SLT exists and options include regimens containing platinum, gemcitabine, and more recently brentuximab vedotin (BV). Complete response rates associated with these regimens range from 50-70%. Due to the increasing use of BV in the front-line setting, development of SLT regimens that are both highly effective and BV-sparing are needed. Programmed death-1 (PD-1) inhibitors are highly active in RR cHL and have the potential to enhance the efficacy of standard chemotherapy. Here we report the results of our phase II study evaluating a novel anti-PD-1-based regimen, pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembrolizumab-GVD), as SLT for RR cHL. Methods: Transplant eligible patients (pts) with RR cHL following failure of 1-line of therapy were eligible. Treatment consisted of 2 to 4 cycles of pembrolizumab (200mg IV, day 1), gemcitabine (1000mg/m2 IV, days 1 and 8), vinorelbine (20mg/m2 IV, days 1 and 8) and liposomal doxorubicin (15mg/m2, days 1 and 8), given on 21-day cycles. Pts who achieved CR by PET (Deauville ≤3) after 2 or 4 cycles proceeded to HDT/AHCT. HDT/AHCT was carried out according to institutional standards and BV maintenance was allowed following HDT/AHCT. The primary endpoint was CR rate after 2 or 4 cycles of pembrolizumab-GVD. Enrollment occurred according to a Simon 2-stage design with sample size based upon a projected CR rate of 70%. In stage 1, 23 pts enrolled and 12 or more CRs were required to proceed to stage II;in stage II, an additional 16 pts enrolled. Out of a total of 39 pts, 24 CRs were required to declare this regimen promising. Results: Among 39 patients enrolled, 37 are evaluable for toxicity (2 pts have not yet started treatment) and 34 are evaluable for response (4 pts too early, 1 pt found to have composite lymphoma after enrollment). Of 37 treated pts, median age is 36 (range 21-71), 43% are male, 23 (62%) had advanced stage disease, and 15 (41%) had primary refractory disease. With regard to RR cHL risk factors (B-symptoms, extranodal disease, and relapse/refractory disease within 1 year of initial treatment), 4(11%) had no risk factors (RFs), 21 (57%) had 1 RF, 9 (24%) had 2 RFs, and 3 (8%) had all 3 RFs. Treatment was well tolerated with most adverse events being grade 1 or 2 (see figure 1). Grade 3 AEs included rash (n=1), elevated AST/ALT (n=3), oral mucositis (n=2), and neutropenia (n=3). Figure 2 shows the outcome for all 37 treated pts. Among 34 evaluable pts, 31 (91%) achieved CR after 2 cycles and 3 achieved partial response. An additional 1 pt achieved CR after 4 cycles of pembrolizumab-GVD, therefore in total, 32 of 34 (94%) achieved CR following pembrolizumab-GVD. 4 pts with CR after 2 cycles received an additional 2 cycles of pembrolizumab-GVD in order to delay HDT/AHCT during the height of the COVID-19 pandemic (n=3) or due to refusing HDT/ASCT (n=1). To date, 32 have undergone HDT/AHCT following 2 (n=27) or 4 (n=5) cycles of treatment. 1 pt is awaiting HDT/AHCT;1 pt refused HDT/ASCT and received pembrolizumab maintenance instead. 2 pts received involved site radiation therapy to initial area of relapsed disease prior to planned HDT/AHCT and 10 pts received post-HDT/ASCT maintenance with BV. Median follow-up post-HDT/AHCT is 9 mos (range 0.03-20.9 mos) and all pts remain in remission to date. Conclusion: Second-line therapy with pembrolizumab-GVD is a highly effective and well-tolerated regimen that can efficiently bridge pts with RR cHL to HDT/AHCT. Updated results including all 39 enrolled pts will be presented at the meeting. Given the high CR rate observed with pembrolizumab-GVD, an expansion cohort evaluating 8 cycles of pembrolizumab maintenance (instead of HDT/AHCT) for patients who achieve CR af er 4 cycles of pembrolizumab-GVD is planned. [Formula presented] Disclosures: Moskowitz: Merck: Consultancy;Incyte: Research Funding;Miragen Therapeutics: Consultancy;Seattle Genetics: Consultancy;Imbrium Therapeutics, L.P.: Consultancy;Merck: Research Funding;Seattle Genetics: Research Funding;Bristol-Myers Squibb: Research Funding. Shah: Amgen Inc.: Research Funding;Janssen: Research Funding. Kumar: AbbVie: Research Funding;Celgene: Honoraria, Other: Honoraria for Advisory Board;Seattle Genetics: Research Funding;Astra Zeneca: Honoraria, Other: Honoraria for Advisory Board;Celgene: Research Funding;Kite Pharmaceuticals: Honoraria, Other: Honoraria for Advisory Board;Adaptive Biotechnologies,: Research Funding;Pharmacyclics: Research Funding. Lahoud: MorphoSys: Other: Advisory Board. Batlevi: Life Sci, GLG, Juno/Celgene, Seattle Genetics, Kite: Consultancy;Janssen, Novartis, Epizyme, Xynomics, Bayer, Autolus, Roche/Genentech: Research Funding. Hamlin: J&J Pharmaceuticals: Research Funding;Portola: Research Funding;Incyte: Research Funding;Portola Pharmaceutics: Consultancy;Juno Therapeutics: Consultancy;Karyopharm: Consultancy;Celgene: Consultancy;Molecular Templates: Research Funding. Straus: Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees;Imedex, Inc.: Speakers Bureau;Targeted Oncology: Consultancy, Speakers Bureau;NY Lymphoma Rounds: Consultancy;Takeda Pharmaceuticals: Research Funding, Speakers Bureau;OncLive: Speakers Bureau;Elsevier: Membership on an entity's Board of Directors or advisory committees, Other: CME writer;ASH: Other: Conference in December 2019 on HL to other physicians during ASH;Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Horwitz: ASTEX: Consultancy;Verastem: Consultancy, Research Funding;Myeloid Therapeutics: Consultancy;Miragen: Consultancy;Kura Oncology: Consultancy;Janssen: Consultancy;GlaxoSmithKline: Consultancy;Daiichi Sankyo: Research Funding;C4 Therapeutics: Consultancy;Affirmed: Consultancy;Vividion Therapeutics: Consultancy;Beigene: Consultancy;Portola: Consultancy, Research Funding;Mundipharma: Consultancy;Innate Pharma: Consultancy;Corvus: Consultancy;Trillium: Consultancy, Research Funding;Seattle Genetics: Consultancy, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Kyowa Hakka Kirin: Consultancy, Research Funding;Infinity/Verastem: Research Funding;Forty Seven: Consultancy, Research Funding;Celgene: Consultancy, Research Funding;Aileron: Consultancy, Research Funding;ADCT Therapeutics: Consultancy, Research Funding. Falchi: Genmab: Research Funding;Roche: Research Funding. Joffe: Epizyme: Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Noy: Pharmacyclics: Research Funding;Pharmacyclics: Consultancy;Janssen: Consultancy;Rafael Pharma: Research Funding;NIH: Research Funding;Morphosys: Consultancy;Medscape: Consultancy;Targeted Oncology: Consultancy. Matasar: Teva: Consultancy;Genentech, Inc.: Consultancy, Honoraria, Research Funding;Merck: Consultancy;Bayer: Consultancy, Honoraria, Research Funding;Juno Therapeutics: Consultancy;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;GlaxoSmithKline: Honoraria, Research Funding;IGM Biosciences: Research Funding;Janssen: Honoraria, Research Funding;Pharmacyclics: Honoraria, Research Funding;Immunovaccine Technologies: Honoraria, Research Funding;Rocket Medical: Consultancy, Research Funding;Takeda: Consultancy, Honoraria;Daiichi Sankyo: Consultancy;Seattle Genetics: Consultancy, Honoraria, Research Funding. Vardhana: Other: Other: SAV has received honoraria from Agios Pharmaceuticals and Rheos Pharmaceuticals, is an advisor for Immunai and has consulted for ADC Therapeutics. von Keudell: Genentech: Research Funding;Bayer: Research Funding;Pharmacyclics: Research Funding. Zelenetz: Novartis: Consultancy;Janssen: Consultancy;Celge e: Consultancy;Amgen: Consultancy;Adaptive Biotechnology: Consultancy;BeiGene: Membership on an entity's Board of Directors or advisory committees;Roche: Research Funding;Gilead: Research Funding;Genentech/Roche: Consultancy;Gilead: Consultancy;Sandoz: Research Funding;Celgene: Research Funding;MEI Pharma: Research Funding;MorphoSys: Research Funding. OffLabel Disclosure: Pembrolizumab as second-line therapy for Hodgkin lymphoma