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190 Background: Metastatic colorectal (CRC), pancreatic (PANC), and gastroesophageal (GE) cancers are the leading causes of GI cancer–related mortality (5-yr survival rate, 14%, 3% and ̃5-6%, respectively). T-cell immunotherapy targeting GI-associated tumor antigens has been attempted, but efficacy has been constrained by on-target off-tumor toxicity, limiting the therapeutic window. The Tmod (TM) platform is an AND-NOT logic-gated CAR T modular system, versions of which have a CEA- or MSLN-targeting CAR activator and a separate HLA-A*02-targeting blocker receptor to protect normal cells. Tmod CAR T exploits HLA LOH, common in GI malignancies (10-33% in primary solid tumors [TCGA]) and can kill tumor cells without harming healthy cells in vitro and in vivo. However, the prevalence of HLA LOH across GI tumors is unknown in the real-world setting. We utilized the Tempus xT oncology NGS database of patients with multiple GI tumors. From a standard-of-care NGS assay, GI cancer patients can be readily identified for HLA LOH and future treatment with Tmod CAR T therapy. Methods: The occurrence of HLA LOH in GI tumors of 1439 patients was assessed using paired germline and somatic DNA sequencing using a research assay [6]. CRC, PANC and GE patients with ≥ stage 3 were then extracted, and rates of HLA LOH were identified (ie, whether loss occurred across high-frequency HLA-A alleles). In addition, mutations in KRAS and BRAF, as well as MSI status were stratified to determine any association with HLA-A LOH. Results: HLA-A LOH was detected in 830 (17.3%) of all solid tumor records, and a similar proportion when all GI cancer records were analyzed (17.0%). For GI subtypes, these values ranged from 13.5% to 23.1% (Table). No high-frequency HLA-A allele (A*01, A*02, A*03, A*11) was more likely to be lost. Clinical biomarkers ( KRAS, BRAF and MSI status) were not associated with HLA-LOH. Conclusions: The frequency of HLA LOH among advanced solid tumor cancers in this dataset is 17.3%, with a range of 13.5-23% between CRC, PANC and GE. The HLA LOH frequency observed in these GI tumors is consistent with that in primary tumors from TCGA, which also used germline-matched and tumor samples. Clinical biomarkers were not associated with HLA LOH. Tempus NGS was able to identify HLA LOH, which can be used for Tmod CAR T therapy to an enhanced therapeutic window. Identification of these patients in BASECAMP-1 (NCT04981119) will enable novel Tmod CAR T therapy. [Table: see text]

PURPOSE Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. METHODS Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. RESULTS Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. CONCLUSION Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.

AbstractPurposeExternal validation of machine learning predictive models is achieved through evaluation of model performance on different groups of patients than were used for algorithm development. This important step is uncommonly performed, inhibiting clinical translation of newly developed models. Machine learning analysis of the Norwegian Knee Ligament Register (NKLR) recently led to the development of a tool capable of estimating the risk of anterior cruciate ligament (ACL) revision (https://swastvedt.shinyapps.io/calculator_rev/). The purpose of this study was to determine the external validity of the NKLR model by assessing algorithm performance when applied to patients from the Danish Knee Ligament Registry (DKLR).MethodsThe primary outcome measure of the NKLR model was probability of revision ACL reconstruction within 1, 2, and/or 5 years. For external validation, all DKLR patients with complete data for the five variables required for NKLR prediction were included. The five variables included graft choice, femur fixation device, KOOS QOL score at surgery, years from injury to surgery, and age at surgery. Predicted revision probabilities were calculated for all DKLR patients. The model performance was assessed using the same metrics as the NKLR study: concordance and calibration.ResultsIn total, 10,922 DKLR patients were included for analysis. Average follow‐up time or time‐to‐revision was 8.4 (± 4.3) years and overall revision rate was 6.9%. Surgical technique trends (i.e., graft choice and fixation devices) and injury characteristics (i.e., concomitant meniscus and cartilage pathology) were dissimilar between registries. The model produced similar concordance when applied to the DKLR population compared to the original NKLR test data (DKLR: 0.68; NKLR: 0.68–0.69). Calibration was poorer for the DKLR population at one and five years post primary surgery but similar to the NKLR at two years.ConclusionThe NKLR machine learning algorithm demonstrated similar performance when applied to patients from the DKLR, suggesting that it is valid for application outside of the initial patient population. This represents the first machine learning model for predicting revision ACL reconstruction that has been externally validated. Clinicians can use this in‐clinic calculator to estimate revision risk at a patient specific level when discussing outcome expectations pre‐operatively. While encouraging, it should be noted that the performance of the model on patients undergoing ACL reconstruction outside of Scandinavia remains unknown.Level of evidenceIII.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have dramatically changed the landscape of cancer therapy. Both remarkable and durable responses have been observed in patients with melanoma, non-small-cell lung cancer (NSCLC), and other malignancies. However, the PD-1/PD-L1 blockade has demonstrated meaningful clinical responses and benefits in only a subset of patients. In addition, several severe and life-threatening adverse events were observed in these patients. Therefore, the identification of predictive biomarkers is urgently needed to select patients who are more likely to benefit from ICI therapy. PD-L1 expression level is the most commonly used biomarker in clinical practice for PD-1/PD-L1 inhibitors. However, negative PD-L1 expression cannot reliably exclude a response to a PD-1/PD-L1 blockade. Other factors, such as tumor microenvironment and other tumor genomic signatures, appear to impact the response to ICIs. In this review, we examine emerging data for novel biomarkers that may have a predictive value for optimizing the benefit from anti-PD-1/PD-L1 immunotherapy.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The “Summary of the Guidelines Updates” section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.

SummaryBackgroundTofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open‐label, long‐term extension study.AimsThe primary objective of OCTAVE Open was to assess the safety and tolerability of long‐term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective.MethodsEligible patients included OCTAVE Induction 1&2 non‐responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient‐years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit).ResultsIn OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient‐years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09‐0.54); serious infections, 1.61 (1.14‐2.20); herpes zoster (non‐serious and serious), 3.16 (2.47‐3.97); opportunistic infections, 0.87 (0.54‐1.33); major adverse cardiovascular events, 0.16 (0.04‐0.42); malignancies (excluding non‐melanoma skin cancer), 1.03 (0.67‐1.52); non‐melanoma skin cancer, 0.75 (0.45‐1.19); deep vein thrombosis, 0.04 (0.00‐0.23); pulmonary embolism, 0.21 (0.07‐0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively.ConclusionTofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long‐term efficacy beyond the 52‐week maintenance study.

Abstract Introduction: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the most common PTCL subtype, accounting for approximately 25% of all PTCL cases. The median age at diagnosis is 60 years and is more prevalent among males. Currently, most epidemiological data on T- and NK-cell lymphomas come from developed countries. Thus, very few data are available regarding this condition in Latin American countries, especially in those aged 60 years and older. The Latin American Group of Lymphoproliferative Disorders (GELL) has previously reported on the impact of serum albumin level in survival outcomes in PTCL-NOS. Therefore, we aim to evaluate the clinical, demographic, and outcome patterns of elderly patients with PTCL-NOS. Methods: We conducted an observational, retrospective study of newly diagnosed PTCL-NOS between January 2000 and December 2020. Patient must be aged 60 years and older. All clinical data were retrieved from clinical records at the different participating institutions. The study outcomes were overall survival (OS) and progression-free survival (PFS). The International Prognostic Index (IPI), the Prognostic Index for T-cell lymphoma (PIT), and the NCCN IPI scores were used for risk stratification. Kaplan-Meier and log-rank test were used for survival analysis. Univariate and multivariate Cox regression analysis were used to estimate hazard ratios (HR) with a 95% confidence interval (CI). Outcomes with a p-value &lt;0.05 were considered statistically significant. Results: A total of 107 patients were included; median age at diagnosis was 72 years (range 60-92), 61% were male, 46% had an ECOG ≥2, 70% had stage III-IV, and 15% had more than one extranodal site. The IPI, PIT and NCCN-IPI scores stratified 51%, 69%, and 74% of patients as high- / high-intermediate risk, respectively. Seventy-four (69%) patients received first-line systemic therapy. Most patients (53%) were managed with CHOP/CHOP-like regimen, followed by CHOEP (19%). The overall response (OR) rate to first-line therapy was 61% (complete response, CR 41%). Salvage therapy was given to only 9 patients; the OR rate was 44% (CR 11%). With a median follow-up of 29 months (95% CI 13-45 months), the 2-year OS was 46% (95% CI 36-59), with median survival time of 16 months (95% CI 10-NR). In the multivariate analysis, patients with serum albumin levels &lt;3.5 g/dL had median survival of 7 months (95% CI 3-20) and 2-year OS rate of 24% (95% CI 13-46%), while patients with albumin ≥3.5 g/dL did not reach the median survival time and had a 2-yOS rate of 67% (95% CI 36-65%) (p&lt;0.0001) (Table 1, Figure 1). Patients with a lymphocyte-to-monocyte ratio (LMR) &gt;7.6 had a median OS of 8 months (95% CI 6-NR) and a 2-year OS of 10% (95% CI 2-65), while patients with a LMR ≤7.6 did not reach the median OS and had a 2-year OS of 57% (95% CI 45-72) (p = 0.0108) (Table 1, Figure 1). Conclusions: This large cohort of Latin American PTCL-NOS patients aged ≥60 years showed overall response rates comparable to previously published data. However, survival rates were shorter compared to those reported in developed countries. In this study, we again confirmed low serum albumin level (&lt;3.5 g/dL) as an adverse prognostic factor for OS in PTCL-NOS, and independent from the IPI, PIT and NCCN-IP scores. Additionally, we describe for first time in a Latin American cohort the impact of the LMR on survival, demonstrating poor outcomes in those with LMR &gt;7.6. We are currently validating our findings in a prospective cohort of Latin American PTCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality. Figure 1 Figure 1. Disclosures Otero: Astra Zeneca: Current Employment. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Abstract Introduction: Renal light chain (AL) amyloidosis typically manifests as proteinuria with or without renal failure and is associated with a risk of progression to renal replacement therapy (RRT). A significant reduction in circulating amyloidogenic light chain is needed to achieve a renal response. Current renal response criteria are binary defining a renal response as &gt;30% reduction in 24-h proteinuria without worsening estimated glomerular filtration rate (eGFR). Several studies suggest that greater reduction in proteinuria following successful therapy improves renal and overall survival. Methods: AL amyloidosis patients diagnosed between 2010 to 2015, achieving at least hematological partial response (hemPR) to therapy and with renal involvement (defined as 24-h non-selective proteinuria &gt;0.5 g/24-h) were included. Four predefined renal response categories were formulated based on reduction level in pretreatment 24-h proteinuria in the absence of renal progression (≥25% decrease in eGFR): renal complete response (renCR, 24-h proteinuria ≤200 mg/24-h); renal very good partial response (renVGPR, &gt;60% reduction in 24-h proteinuria); renal partial response (renPR, 31-60% reduction in 24-proteinuria); and renal no response (renNR, 30% or less reduction). Renal response was assessed at landmark (6-, 12-, and 24 months from treatment initiation) and as best renal response. Graded renal responses were assessed as predictors for time from diagnosis to RRT and overall survival. Results: Seven hundred and thirty-seven patients were included. The median age was 63. The breakdown of renal stage was: I, 34%; II, 52%; and III, 14%. Eighty percent of patients received 1 line of therapy within 12 months of their diagnosis. Bortezomib-based therapy was given to 60% of the patients; 28% received autologous stem cell transplantation (ASCT) as their first line therapy. Hematological CR was achieved in 44% of patients, followed by hematological very good partial response (38%) and hemPR (18%). RRT was required during follow-up in 15% of patients (n=108) with a median time from diagnosis to RRT of 18 (IQR 6-43) months. Twenty-eight percent of the patients died. The median follow-up of the surviving patients was 69 months (IQR 56-86). Reduction in 24-h proteinuria from baseline improved over time with a median reduction of 34%, 50% and 71% at 6-month, 12-month, and 24-months, respectively. At best response, renCR, renVGPR, renPR and renNR were achieved in 27% (n=199), 34% (n=247), 15% (n=112) and 24% (n=179) of patients, respectively. The median time to best renal response among renal responders was 17 (IQR 8-31) months, longer for renCR (23 months, IQR 10-40) compared to renVGPR (16 months, IQR 9-27) or renPR (11 months, IQR 6-19). A renal response as early as 6 months after therapy initiation was able to predict time to RRT with an increase in RRT risk with lower level of renal response at that time point (5-year RRT risk 0%, 3%, 9% and 16% for renCR, renVGPR, renPR and renNR, respectively, P&lt;0.001, Figure 1A). Prediction of risk for RRT based on renal response depth improved at 12- and 24-months (Figure 1B-C) and at best renal response (Figure 1D). Overall survival discrimination based on renal response depth was noted as early as 12 months from therapy initiation and improved with time. Renal response criteria as best response were tested in a univariate analysis and multivariable proportional hazard models for time to RRT and OS. The graded renal response criteria demonstrated an independent prognostic role for time to RRT and OS. Along with renal stage, graded renal responses were the strongest predictors for time to RRT. Conclusions: We validated new graded renal response criteria based on reduction in 24-h proteinuria. These 4-level renal response criteria highlight the importance of achieving a deep renal response to improve renal and overall survival. These findings will allow clinicians to make decisions on therapy changes or augmentation based on response depth as early as 6-months, before irreversible renal failure develops. Figure 1 Figure 1. Disclosures Palladini: Janssen Global Services: Honoraria, Other: advisory board fees; Siemens: Honoraria; Pfizer: Honoraria. Milani: Celgene: Other: Travel support; Janssen-Cilag: Honoraria. Schönland: Sanofi: Research Funding; Prothena: Honoraria, Other: Travel grants; Janssen: Honoraria, Other: Travel grants, Research Funding; Takeda: Honoraria, Other: Travel grants; Pfizer: Honoraria. Hegenbart: Akcea: Honoraria; Alnylam: Honoraria; Janssen: Consultancy, Research Funding; Prothena: Research Funding; Pfizer: Consultancy, Honoraria. Dispenzieri: Oncopeptides: Consultancy; Alnylam: Research Funding; Sorrento Therapeutics: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Janssen: Consultancy, Research Funding. Kumar: Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy; Carsgen: Research Funding; Beigene: Consultancy; Novartis: Research Funding; Bluebird Bio: Consultancy; Amgen: Consultancy, Research Funding; Roche-Genentech: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Antengene: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Kastritis: Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding. Dimopoulos: Takeda: Honoraria; Janssen: Honoraria; Beigene: Honoraria; BMS: Honoraria; Amgen: Honoraria. Liedtke: Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Trial Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Alnylam: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Witteles: Pfizer: Honoraria, Research Funding; Alnylam: Honoraria, Research Funding; Eidos: Research Funding. Sanchorawala: Pfizer: Honoraria; Takeda: Research Funding; Celgene: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Regeneron: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptide: Research Funding; Karyopharm: Research Funding; Sorrento: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees, Research Funding. Landau: Takeda, Janssen, Caelum Biosciences, Celgene, Pfizer, Genzyme: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Genzyme: Honoraria. Cibeira: Celgene: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Akcea: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wechalekar: Caelum Biosciences: Other: Clinical Trial Funding; Amgen: Research Funding; Janssen: Consultancy; Celgene: Honoraria; Takeda: Honoraria; Alexion, AstraZeneca Rare Disease: Consultancy. Gertz: Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy; Aurora Biopharma: Other: Stock option; Ionis Pharmaceuticals: Other: Advisory Board; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring; Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria.

Abstract Introduction: Autoimmune Hemolytic Anemia (AIHA) is caused by autoantibodies that react with red blood cells (RBCs) resulting in predominantly extravascular hemolysis in an FcR and/or complement-dependent manner. In warm AIHA (wAIHA), autoantibodies are generally of the IgG isotype, while in cold agglutinin disease (CAD) they are predominantly of the IgM isotype. It is well established that the classical complement cascade is critical for the pathogenesis of CAD based on therapeutic clinical studies. Published data also suggest that complement activation plays a role in wAIHA, although it is not clear which patients would most benefit from complement-based therapy. To help address this question, we utilized an assay that measures the ability of autoantibodies in patient sera to induce complement deposition on the surface of donor RBCs (based on Meulenbroek, et al., 2015). Methods: Sera were collected retrospectively from 12 wAIHA patients whose direct antiglobulin tests (DAT) were either IgG+/C3+ or IgG+/C3-. Sera retrospectively collected from two CAD patients were used as positive controls. Individual patient sera were examined in the in vitro complement deposition assay using RBCs from type O+ healthy donors. RBCs and sera were incubated at 37 oC in the presence of either EDTA or an inhibitory antibody against C1q as inhibitors of the classical pathway. RBCs were then stained and processed by flow cytometry to determine the level of C4 deposition. Results: Sera from both CAD patients deposited C4 on the surface of ~70% of healthy human RBCs in vitro. Four out of twelve (33%) sera from wAIHA patients displayed this activity, and all four of these patients were identified as IgG+/C3+ on DAT. Complement deposition ranged from ~10-60% of the RBCs in wAIHA, suggesting heterogeneity in antibody activity for complement deposition in sera from wAIHA patients. Addition of EDTA or an inhibitory antibody against C1q fully blocked deposition of C4 on RBCs by wAIHA sera, indicating dependence of the classical complement pathway. These results indicate differences in the frequency of classical pathway involvement in CAD versus wAIHA and may help identify a subset of wAIHA patients most likely to respond to anti-C1q therapy. Conclusions: The hypothesis of classical complement cascade involvement in wAIHA disease in a subset of patients is supported by our results. Critically, complement deposition on the surface of cells by anti-C1q prevented the deposition of a downstream complement marker, C4. Inhibition of C1q has been shown to block activation of all downstream classical complement components, including C3b and C4b involved in extravascular hemolysis and C5b involved in direct cell lysis. The therapeutic potential of blocking classical complement pathway activity in wAIHA is currently being evaluated in an ongoing Phase 2 interventional trial (NCT04691570) assessing efficacy of an anti-C1q drug candidate in wAIHA patients, focusing on those with evidence of classical complement pathway activity. Disclosures Teigler: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Low: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Rose: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Cahir-Mcfarland: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Yednock: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Kroon: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Keswani: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Barcellini: Novartis: Honoraria; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Research Funding; Alexion Pharmaceuticals: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees.