IMPORTANCEIn observational oncology studies of solid tumors, response to treatment can be evaluated based on electronic health record (EHR) documentation (clinician-assessed response [CAR]), an approach different from standardized radiologist-measured response (Response Evaluation Criteria in Solid Tumours [RECIST] 1.1). OBJECTIVE To evaluate the feasibility of an imaging response based on RECIST (IRb-RECIST) and the concordance between CAR and imaging response based on RECIST assessments, and investigate discordance causes. DESIGN, SETTING, AND PARTICIPANTS This cohort study used an EHR-derived, deidentified database that included patients with stage IV non-small cell lung cancer (NSCLC) diagnosed between January 1, 2011, to June 30, 2019, selected from 3 study sites. Data analysis was conducted in August, 2020.EXPOSURES Undergoing first-line therapy and imaging assessments of response to treatment. MAIN OUTCOMES AND MEASURESIn this study, CAR assessments (referred to in prior publications as "real-world response" [rwR]) were defined as clinician-documented changes in disease burden at radiologic evaluation time points; they were abstracted manually and assigned to response categories. The RECIST-based assessments accommodated routine practice patterns by using a modified version of RECIST 1.1 (IRb-RECIST), with independent radiology reads. Concordance was calculated as the percent agreement across all response categories and across a dichotomous stratification (response [complete or partial] vs no response), unconfirmed or confirmed. RESULTSThis study found that, in 100 patients evaluated for concordance, agreement between CAR and IRb-RECIST was 71% (95% CI, 61%-80%), and 74% (95% CI, 64%-82%) for confirmed and unconfirmed response, respectively. There were more responders using CAR than IRb-RECIST (40 vs 29 with confirmation; 64 vs 43 without confirmation). The main sources of discordance were the different use of thresholds for tumor size changes by RECIST vs routine care, and unavailable baseline or follow-up scans resulting in inconsistent anatomic coverage over time. CONCLUSIONS AND RELEVANCEIn this cohort study of patients with stage IV NSCLC, we collected routine-care imaging, showing the feasibility of response evaluation using IRb-RECIST criteria with independent centralized review. Concordance between CAR and centralized IRb-RECIST was moderate. Future work is needed to evaluate the generalizability of these results to broader populations, and investigate concordance in other clinical settings.

We included individuals who reported any cancer diagnosis of any type (first primary cancer diagnosis). The outcome was whether an individual had a diagnosis of a second primary obesityrelated cancer, defined as obesity-related cancer diagnosed in the year after the year

Introduction: Hypogammaglobulinemia is a known potential adverse event in patients with CLL receiving anti-CD20 monoclonal antibody (mAb) therapy. However, real-world immunoglobulin G (IgG) testing rates have not been extensively studied. We used a real-world database to investigate IgG testing rates in patients with CLL before and after anti-CD20 exposure. We further examined factors that increased the likelihood of new onset hypogammaglobulinemia following anti-CD20 therapy. Methods: The Flatiron Health EHR-derived de-identified database was used to select patients with abstraction-confirmed CLL diagnosed before 6/1/2020 with: (1) Exposure to an anti-CD20 mAb, (2) At least one IgG lab within 180 days prior to first anti-CD20 line start, and (3) No evidence of hypogammaglobulinemia (IgG < 7g/L) within 6 months prior to first anti-CD20 line start. A "hypogammaglobulinemia detection window" was defined for each patient as the time between first anti-CD20 administration through to 365 days thereafter. Patients were grouped into 3 categories: (A) "Unknown status": those with no IgG testing during the window, (B) "Confirmed hypogam": those with hypogammaglobulinemia detected on any test during the window, and (C) "No detected hypogam": those tested for IgG during the window with 0 tests meeting the hypogammaglobulinemia threshold. Demographic and clinical baseline characteristics were compared across the groups. A logistic regression was performed to compare factors associated with higher likelihood of detecting hypogammaglobulinemia among patients with an IgG test in the detection window. Factors included were: patient age at start of detection window, exposure to chemotherapy before detection window (Y/N), concurrent chemotherapy to anti-CD20 during the detection window (Y/N), and whether anti-CD20 was given in the first line (1L) setting (Y/N). We also performed a separate scenario analysis with outcome of severe hypogammaglobulinemia (IgG < 5 g/L, compared to < 7 g/L in primary analysis). Results: We found 5,838 anti-CD20 mAb-exposed patients with CLL, of which 1,927 (33%) had at least 1 IgG lab within 180 days of anti-CD20 start. Of those, 922 (48%) had hypogammaglobulinemia within 6 months prior to starting anti-CD20 therapy, leaving 1,005 patients in the cohort. 526 patients (52%) fell into the 'unknown status' category. 182 (18%) patients fell into the 'confirmed hypogam' category, and 297 (30%) fell into the 'no hypogam detected' category. Patients across these 3 categories had similar baseline characteristics (Table 1). Among the patients with an IgG test in the detection window (N=479), patients with 'confirmed hypogam' had more IgG tests during the window than the patients with 'no detected hypogam' (mean 3.9 vs. 2.8 tests, p<0.001). Results of the logistic regression for IgG < 7 g/L did not yield any factors significantly associated with higher likelihood of hypogammaglobulinemia (Table 2). However, the regression at IgG < 5 g/L (incl. changing cohort inclusion criteria 3, N=703) found that concurrent exposure to chemotherapy was associated with higher likelihood of severe documented hypogammaglobulinemia (odds ratio 1.89; 95% CI 1.23-2.96; p = 0.004). Conclusions: In this real-world cohort of patients with CLL with at least one IgG test within 6 months prior to anti-CD20 mAb initiation, hypogammaglobulinemia was common. A majority of the cohort was not tested for IgG post anti-CD20 mAb initiation, which likely reflects clinical practice of infrequently obtaining IgG levels in patients with normal pre-treatment IgG levels. As clinically expected, patients with hypogammaglobulinemia were tested for IgG more frequently than those who were not. This hypothesis-generating study suggests that administering chemotherapy concurrently to anti-CD20 mAbs increases the likelihood of documented severe hypogammaglobulinemia (IgG < 5g/L) in patients with CLL. Further research should confirm this. Our analyses did not account for patients who may have had transient hypogammaglobulinemia during anti-CD20 treatment, and did not stratify by intravenous immunoglobulin (IVIG) usage in this population. Further research should examine the effect of anti-CD20-associated hypogammaglobulinemia on outcomes, and determine if IgG surveillance should be standardized as part of clinical guidelines. Disclosures Hooley: Flatiron Health Inc: Current Employment, Research Funding; Roche Group: Current equity holder in publicly-traded company. Maignan:Flatiron Health Inc: Current Employment, Research Funding; Roche Group: Current equity holder in publicly-traded company. Jacob:Flatiron Health Inc: Current Employment, Research Funding; Roche Group: Current equity holder in publicly-traded company. Medina:Flatiron Health Inc: Current Employment, Research Funding; Roche Group: Current equity holder in publicly-traded company. Benderoff:Roche Group: Current equity holder in publicly-traded company; Flatiron Health Inc: Current Employment, Research Funding. Chen:Flatiron Health Inc: Current Employment, Research Funding; Roche Group: Current equity holder in publicly-traded company. Huntington:AbbVie: Consultancy; Astrazeneca: Honoraria; Bayer: Consultancy, Honoraria; Celgene: Consultancy, Research Funding; DTRM: Research Funding; Genentech: Consultancy; Novartis: Consultancy; Pharmacyclics: Honoraria; TG Therapeutics: Research Funding.

Introduction Front-line treatment for patients with active chronic lymphocytic leukemia (CLL) often includes an anti-CD20 monoclonal antibody. However, treatment with anti-CD20 therapy has the potential to reactivate latent hepatitis B virus (HBV). Thus, in 2015 an American Society of Clinical Oncology (ASCO) panel advised screening all patients for HBV infection before starting anti-CD20 therapies. Both Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (HBcAb) testing are required for proper screening. In addition, the ASCO panel recommended testing for both IgM and IgG isotypes of HBcAb, as patients with remote HBV infection may have undetectable levels of HBcAb IgM. We evaluated guideline adherence for HBV testing in a large, real-world cohort of patients with CLL. Methods This retrospective analysis leveraged data derived from electronic health records (EHRs) in the Flatiron Health database. The database included 7,795 patients with CLL who received at least one order for an antineoplastic treatment between January 1, 2011 and May 31, 2018. We included only patients who received an anti-CD20 therapy (rituximab, ofatumumab, obinutuzumab) and excluded patients whose start of CLL treatment (as captured through chart abstraction) was >30 days before the start of structured EHR data (N=4,288). Using structured EHR data (based on Logical Observation Identifiers Names and Codes [LOINC]), we evaluated the frequency of HBsAg and HBcAb testing, including a separate analysis of HBcAb IgM and IgG testing. Results Of 4,288 patients in the cohort treated with anti-CD20, 2,034 (47%) had evidence of HBV testing at any point during their care, and 1,765 (41%) had evidence of HBV testing at any point prior to and up to 90 days following anti-CD20 therapy initiation. Over time, the proportion of HBV infection testing up to 90 days following anti-CD20 treatment initiation increased steadily, from <15% in early 2011, reaching as high as 70% in 2017 (Figure). Following the ASCO guideline publication in 2015, the proportion of patients tested for both HBsAg and HBcAb increased by 33%, while the proportion of HBsAg-only tested patients dropped by 35% (Table). However, even if unspecified HBcAb tests are assumed to represent testing for both IgG and IgM isotypes, in the most recent timeframe nearly half (46%) of the patients who were tested did not receive the requisite screening tests (i.e., for both isotypes). Additionally, nearly 20% received only one test (HBsAg or HBcAb) and another 25% received both tests but the HBcAb test was for the IgM isotype alone (Table). Discussion In this real-world cohort of patients with CLL treated with anti-CD20 therapies, overall HBV testing increased throughout the study period, in accordance with ASCO guidelines. Although the most recent data points may not yet capture testing up to 90 days following treatment initiation, and HBV testing information for some patients may not be captured in the EHR, our findings suggest that a sizable proportion of patients are not receiving appropriate screening for HBV. In addition, a significant proportion (25%) of patients were tested for both HBsAg and HBcAb, but the HBcAb test was for the IgM isotype alone, which could result in a false negative test and missed cases of latent HBV. These findings suggest a need for additional quality improvement efforts. Further research is needed to determine demographic and clinical characteristics of tested versus untested patients, and whether testing is associated with reduced risk of liver failure in patients undergoing anti-CD20 therapy. Disclosures Hooley: Flatiron Health: Employment. Chen:MedCyclops LLC: Equity Ownership; Nootrobox: Consultancy; Flatiron Health: Employment. Maignan:Flatiron Health: Employment. Carson:Roche: Consultancy; Washington University in St. Louis: Employment; Flatiron Health: Employment.

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