Citations

TPS234 Background: Total neoadjuvant therapy (TNT) followed by total mesorectal excision (TME) is one of the standard treatment options for patients with locally advanced rectal cancer (LARC). A commonly employed TNT protocol consists of 8 biweekly cycles of oxaliplatin-based chemotherapy (CT) followed by radiation concurrent with fluoropyrimidine-based chemotherapy (CRT) for about 6 weeks. During the TNT, patients undergo tumor response assessments periodically with standard modalities (SM) consisting of pelvic magnetic resonance imaging (MRI) and proctoscopic/endoscopic examination. The objective of the current protocol is to evaluate the feasibility of tumor response assessment by ctDNA in patients with LARC undergoing TNT. The present feasibility study is designed to collect preliminary data to evaluate if a subsequent larger validation study is justified. If ctDNA-based response assessment is validated, ctDNA can potentially replace at least some components of the SM (for example, MRI) as tumor response assessment by SM is often time-consuming, expensive, and poses logistical challenges. Methods: Patients with LARC undergoing TNT will be enrolled. After obtaining informed consent, venous blood samples will be obtained for ctDNA level measurements at the following time points: baseline (within 1 week before the CT begins), after 4 cycles of CT within +/- 5 days of the MRI study, after 8 cycles of CT within +/- 5 days of the MRI study, and 1 to 14 days before TME. ctDNA levels will be measured by a commercially available ctDNA assay (Signatera by Natera), and ctDNA response is defined as >90% drop in the ctDNA level after treatment compared to the baseline level. Tumor response will be evaluated after 4 and 8 cycles of CT by SM. Primary endpoint: correlation between the response rate (RR) assessed by ctDNA and by SM after 4 cycles of CT. Secondary endpoints: 1) correlation between the RR assessed by ctDNA and by SM after 8 cycles of CT, and 2) correlation between the ctDNA defined RR and the complete pathological response (pCR) rate. The trial will enroll 30 patients. To evaluate the primary endpoint, differences in ctDNA levels between the baseline and 4-cycles post-CT will be computed. The differences will then be expressed as a proportion of each patient’s baseline level, D. This relative change, D, will be compared between the responder and non-responder groups using a two-sample Welch’s t-test. Similar methods will be applied for the secondary endpoints. All analyses will use the nominal type I error level of 0.05 and two-sided tests. Clinical trial information: NCT04670588.

656 Background: Non-neutropenic enterocolitis (NNEC), a potentially fatal toxicity of capecitabine (CAPE), is under-reported in the literature. An institutional review was performed to determine the incidence, clinical course, and outcome of patients developing CAPE-induced NNEC. Methods: After the institutional review board approval, a database search identified patients requiring inpatient care for CAPE-induced diarrhea over a period of 6 years (between 01/2015 and 12/2020). Among the patients requiring hospital admission, patients with radiologic features of enterocolitis were included in the analysis. Data on patient characteristics, imaging study results, clinical course, and outcomes were gathered by electronic chart review. Results: Among the 789 patients treated with CAPE, 25 patients (3%) developed grade 3 or higher diarrhea requiring hospital admission, and 13 out of these 25 patients (1.6 % of patients treated with CAPE) had evidence of enterocolitis on CT scan: ileitis in 7/13 (54%), colitis in 1/13 (8%), and both in 5/13 (38%) patients. The median age of the patient cohort was 64 years (range, 31-81), 8/13 (62%) were female, and all patients were Caucasian. CAPE was administered for the following indications: breast cancer in 6 patients, colorectal cancer in 4 patients, cholangiocarcinoma in 2 patients, and neuroendocrine tumor in 1 patient. ECOG performance status at the time of CAPE initiation was 0 in 7 patients and 1 in 6 patients. Most patients (7/13, 54%) received single-agent CAPE, and the majority (10/13, 77%) developed diarrhea with the first cycle after a median of 21 days (range, 10-50). Patients were hospitalized after a median of 27 days (range, 13-51), and the median hospital stay was 12 days (range, 4-25). None of the 13 patients demonstrated neutropenia at the time of hospital admission. The associated adverse effects at the time of admission included grade 3 abdominal pain in 8 (62%) patients, grade 3 nausea in 7 (54%) patients, and grade 3 vomiting in 3 (23%) patients. Hypokalemia and oral mucositis were present at admission in 6 (46%) and 2 (15%) patients, respectively. Stool studies performed in 11 (85%) patients ruled out infection. Testing for dihydropyrimidine dehydrogenase deficiency performed in 4 (31%) patients was negative. All patients were treated with supportive measures, and 2 (15%) patients required total parenteral nutrition. All but 1 patient recovered fully; 1 patient died due to a condition unrelated to CAPE. Intravenous infusional 5-fluorouracil (5-FU) administration in 3 patients after the recovery was tolerated well. Conclusions: CAPE-induced NNEC is uncommon and generally occurs after the first cycle of therapy. Most patients developing CAPE-induced NNEC recover fully with appropriate supportive measures. Infusional 5-FU-based regimens appear to be safe in this patient group.

44 Background: Despite an alarming rise in incidence, data on survival outcome and treatment response of young-onset (age < 50 years) locally advanced rectal cancer (YO-LARC) patients receiving total neoadjuvant therapy (TNT) are sparse. We retrospectively compared the outcome between YO-LARC and later-onset (aged 50 years or older) LARC (LO-LARC) patients treated with TNT. Methods: After the institutional review board approval, electronic medical records of the LARC (T3/T4 or node-positive) patients treated with TNT at a tertiary care cancer center between January 1, 2015, and June 30, 2020, were reviewed for data collection. TNT consisted of systemic chemotherapy with oxaliplatin-based regimens for 16 weeks followed by long-course radiation with concurrent capecitabine or 5-fluorouracil (CRT). Patients receiving only preoperative CRT were excluded. Most patients underwent surgical resection following the TNT. Non-operative management was offered to patients if TNT resulted in clinical complete response (cCR). The following comparisons between the YO-LARC and the LO-LARC patients were performed: patient characteristics, pathological complete response (pCR) rate, combined pCR + cCR rate, disease-free survival (DFS), and overall survival (OS). Results: Of 72 patients included in the analysis, 44(61%) were male, 49 (68%) were Caucasian, and 62 (86%) had clinical stage III disease. The study included 26 (36%) patients with YO-LARC (median age, 43 years) and 46 (64%) patients with LO-LARC (median age, 64 years). The comparison of patient characteristics that included gender, clinical stage, baseline carcinoembryonic antigen level, the distance of the tumor from the anal verge, presence of high-risk features, and histologic grade did not differ significantly between the groups. There were no statistically significant differences in pCR and combined pCR+cCR rates (p = 0.16) between the groups: YO-LARC, 12 % (3/26) and 15 % (4/26), respectively; LO-LARC, 22% (10/46) and 30% (14/46), respectively. Either group did not reach median DFS and OS after a median follow-up of 38 months for survivors. The estimated 5-year OS rates in patients with YO-LARC and LO-LARC were 86 % (95% confidence interval [CI], 69% to 100%) and 84% (95% CI, 68% to 100%), respectively (p = 0.92). The estimated 3-year DFS rates in patients with YO-LARC and LO-LARC were 67 % (95% CI, 50% to 89%) and 83% (95% CI, 72% to 95%), respectively (p = 0.19). Conclusions: The current retrospective analysis did not demonstrate significant differences in the pCR rates, combined pCR +cCR rates, DFS, or OS between the YO-LARC and LO-LARC patients treated with TNT.

AbstractBackgroundMalnutrition is underrecognized and underdiagnosed, despite high prevalence rates and associated poor clinical outcomes. The involvement of clinical nutrition experts, especially physicians, in the care of high‐risk patients with malnutrition remains low despite evidence demonstrating lower complication rates with nutrition support team (NST) management. To facilitate solutions, a survey was designed to elucidate the nature of NSTs and physician involvement and identify needs for novel nutrition support care models.MethodsThis survey assessed demographics of NSTs, factors contributing to the success of NSTs, elements of nutrition education, and other barriers to professional growth.ResultsOf 255 respondents, 235 complete surveys were analyzed. The geographic distribution of respondents correlated with population concentrations of the United States (r = 90.8%, p < .0001). Most responding physicians (46/57; 80.7%) reported being a member of NSTs, compared with 56.5% (88/156) of dietitians. Of those not practicing in NSTs (N = 81/235, 34.4%), 12.3% (10/81) reported an NST was previously present at their institution but had been disbanded. Regarding NSTs, financial concerns were common (115/235; 48.9%), followed by leadership (72/235; 30.6%), and healthcare professional (HCP) interest (55/235; 23.4%). A majority (173/235; 73.6%) of all respondents wanted additional training in nutrition but reported insufficient protected time, ability to travel, or support from administrators or other HCPs.ConclusionCore actions resulting from this survey focused on formalizing physician roles, increasing interdisciplinary nutrition support expertise, utilizing cost‐effective screening for malnutrition, and implementing intervention protocols. Additional actions included increasing funding for clinical practice, education, and research, all within an expanded portfolio of pragmatic nutrition support care models.

AbstractBackgroundThere is a need to better understand the overall state of sub‐specialization in physical medicine and rehabilitation (PM&R).ObjectiveTo examine the status and trends in subspecialty certification for each of the seven subspecialties approved for American Board of Physical Medicine and Rehabilitation (ABPMR) diplomates.Design/SettingRetrospective analysis of deidentified information from the ABPMR database.ParticipantsPhysicians certified by ABPMR through 2019.InterventionsNot applicable.Main Outcome MeasuresFor each subspecialty, we examined: (1) the number of certificates issued to ABPMR diplomates; (2) the recertification rate; (3) the yearly trends for total active, new, and expired certificates; and (4) for ABPMR‐administered subspecialties, recertification rates for those entering the subspecialty through fellowship completion versus a “grandfathered” practice pathway.ResultsOf 11,421 ABPMR diplomates in the United States in 2019, a total of 3560 (31.2%) had 3985 active subspecialty certificates. Pain Medicine (PM) was the most common subspecialty certification (15.5% of all ABPMR diplomates) followed by Sports Medicine (SM, 6.6%), Brain Injury Medicine (BIM, 4.8%), Spinal Cord Injury Medicine (SCIM, 4.2%), Pediatric Rehabilitation Medicine (PRM, 2.5%), Neuromuscular Medicine (NMM, 0.7%), and Hospice and Palliative Medicine (HPM, 0.5%). For diplomates with more than one subspecialty certification, PM and SM was the most frequent combination. Both the recertification rate and the end of practice track eligibility influenced certification trends differently for individual subspecialties. The average number of new certificates added annually for every subspecialty was higher before than after the temporary practice track‐based eligibility ended; the difference was statistically significant (p < .05) for SCIM, PM, SM, and NMM. The recertification rate for all subspecialties combined was 73.4%. For the subspecialties (SCIM, PRM) for which these data were available, fellowship candidates had higher recertification rates than those grandfathered through a practice track.ConclusionThis report informs stakeholders about the state and evolution of subspecialty certification in PM&R over time.

Abstract Recent advances in the science and technology of artificial intelligence (AI) and growing numbers of deployed AI systems in healthcare and other services have called attention to the need for ethical principles and governance. We define and provide a rationale for principles that should guide the commission, creation, implementation, maintenance, and retirement of AI systems as a foundation for governance throughout the lifecycle. Some principles are derived from the familiar requirements of practice and research in medicine and healthcare: beneficence, nonmaleficence, autonomy, and justice come first. A set of principles follow from the creation and engineering of AI systems: explainability of the technology in plain terms; interpretability, that is, plausible reasoning for decisions; fairness and absence of bias; dependability, including “safe failure”; provision of an audit trail for decisions; and active management of the knowledge base to remain up to date and sensitive to any changes in the environment. In organizational terms, the principles require benevolence—aiming to do good through the use of AI; transparency, ensuring that all assumptions and potential conflicts of interest are declared; and accountability, including active oversight of AI systems and management of any risks that may arise. Particular attention is drawn to the case of vulnerable populations, where extreme care must be exercised. Finally, the principles emphasize the need for user education at all levels of engagement with AI and for continuing research into AI and its biomedical and healthcare applications.

Aim There is an association between heart failure with preserved ejection fraction (HFpEF) and insulin resistance, but less is known about the diabetic continuum, and in particular about pre‐diabetes, in HFpEF. We examined characteristics and outcomes of participants with diabetes or pre‐diabetes in PARAGON‐HF. Methods and results Patients aged ≥50 years with left ventricular ejection fraction ≥45%, structural heart disease and elevated N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were eligible. Patients were classified according to glycated haemoglobin (HbA1c): (i) normal HbA1c, <6.0%; (ii) pre‐diabetes, 6.0%–6.4%; (iii) diabetes, ≥6.5% or history of diabetes. The primary outcome was a composite of cardiovascular (CV) death and total heart failure hospitalizations (HFH). Of 4796 patients, 50% had diabetes and 18% had pre‐diabetes. Compared to patients with normal HbA1c, patients with pre‐diabetes and diabetes more often were obese, had a history of myocardial infarction and had lower Kansas City Cardiomyopathy Questionnaire scores, while patients with diabetes had more clinical evidence of congestion, but similar NT‐proBNP concentrations. The risks of the primary composite outcome (rate ratio [RR] 1.59, 95% confidence interval [CI] 1.35–1.88), total HFH (RR 1.67, 95% CI 1.39–2.02) and CV death (hazard ratio [HR] 1.35, 95% CI 1.07–1.71) were higher among patients with diabetes, compared to those with normal HbA1c. Patients with pre‐diabetes had a higher risk (which was intermediate between that of patients with diabetes and those with normal HbA1c) of the primary outcome (HR 1.27, 95% CI 1.00–1.60) and HFH (HR 1.35, 95% CI 1.03–1.77), but not of CV death (HR 1.02, 95% CI 0.75–1.40). Patients with diabetes treated with insulin had worse outcomes than those not, and those with ‘lean diabetes’ had similar mortality rates to those with a higher body mass index, but lower rates of HFH. Conclusion Pre‐diabetes is common in patients with HFpEF and is associated with worse clinical status and greater risk of HFH. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT01920711.

Abstract Background Although uncommon, nontuberculous mycobacterial infections (NTMI) of the upper extremity cause significant morbidity based on their natural history, delay in diagnosis, prolonged duration of antimicrobial therapy often combined with surgical debridement, and functional loss. Herein we describe our experience with such infections. Methods Records for adult patients from two academic, tertiary facilities with culture-proven NTMI involving the upper extremity were retrospectively reviewed. Demographic information, co-morbidities, laboratory and microbiological evaluation, management, and outcomes were extracted. Patients were analyzed based on pathogen identified and immune suppression. Results 77 patients were identified. The mean age was 59 years and 65% of patients were male. 48% reported a preceding injury, with the hand being most frequently involved (58%). 41% were considered immune compromised; 19% of them were organ transplant recipients. Mean symptom duration prior to presentation was 203 days. Mean time to culture identification was 33 days, and 25 different species of NTM were identified (subcategorized as rapid or slow growers). 77% had solitary lesions, with cutaneous/subcutaneous location as the most common site. All patients underwent surgical debridement with four undergoing amputation to control infection. 69% received combination antimicrobial therapy for a mean duration of 184 days. Immunosuppressed patients were treated with antimicrobial therapy for a longer duration (mean 243 vs 155 days). One-third of patients experienced complications and/or recurrence regardless of organism type. Conclusion NTMI of the upper extremity is often misdiagnosed leading to significant delays in appropriate management. Knowledge of its protean manifestations and early consideration in the differential diagnosis of chronic, painful swelling of the hand or wrist, nodular or inflammatory lesions, or septic arthritis is crucial. A low threshold for surgical or biopsy with specimens sent for histopathology as well as microbiologic analysis is warranted. A combined approach with surgical debridement and prolonged combination antimicrobial therapy is necessary for optimal outcomes; however, adverse reactions from such therapy are commonly encountered. Disclosures All Authors: No reported disclosures

Abstract TGFβ plays a pivotal role in the pathobiology of myelofibrosis (MF) by not only promoting bone marrow fibrosis (BMF) but also by enhancing the dormancy of normal but not MF hematopoietic stem cells (HSCs). TGFβ has also previously been reported to inhibit normal megakaryocyte (MK) production (Bruno et al Blood 1998). TGFβ1 promotes the synthesis of collagen by normal human mesenchymal stromal cells (MSCs). Treatment of MSCs with AVID200, a potent TGFβ1/3 protein trap, significantly decreased MSC proliferation, phosphorylation of SMAD2, and collagen expression. Robust expression of pSMAD2 was observed in the absence of exogenous TGFβ in normal donor or MF-MKs, Addition of AVID200 to MKs decreased pSMAD2 without affecting total SMAD2/3 and led to increased numbers of MKs. Treatment of MF MNCs with AVID200 also led to increased numbers of progenitor cells with wild type JAK2 and a reduction of mutated colonies. A phase 1b trial of AVID200 (NCT03895112) was performed and completed in INT-2/high risk MF patients resistant/intolerant to ruxolitinib (rux); baseline platelet count of ≥ 25 x 10 9/L, and grade 2/3 BMF. Subjects received AVID200 intravenously on Day 1 of a 21 day cycle. Response was assessed by IWG/ELN criteria after 6 cycles of AVID200. Subjects attaining at least a CI or SD with a decrease in BMF by ≥1 grade, continued AVID200. We previously presented the results of the dose escalation study (Mascarenhas ASH 2020) demonstrating that AVID200 was well tolerated without dose limiting toxicities at 3 tested dose levels (Lots A and B) in dose cohorts of 180 mg (A), 550 mg (A)/70 mg (B), and 180 mg (B). Here we report updated safety and efficacy results of the phase 1b dose expansion stage at the two highest doses tested (70 mg (B) and 180 mg (B). Twenty-two subjects were enrolled (1 withdrew before receiving treatment) and 9 were treated with AVID200 in the dose escalation phase and 12 in the dose expansion phase [Table1]. Median time after rux discontinuation was 7.4 months (0.5-59.9). The most common mutations observed at baseline in this cohort included JAK2V617F (71%), TET2 (29%) ASXL1 (24%) and CALR (19%). (Fig 1) No DLTs were observed and Grade 3/4 AEs were observed in 16 (76.2%) subjects. Grade 3/4 non-hematologic AEs were observed in 8 (38.1%) subjects and included one subject in each case (epistaxis, mucositis, extraocular muscle paresis, fatigue, rash, duodenal hemorrhage, gastric hemorrhage, urinary tract infection, and syncope). Grade 3/4 hematologic AEs were anemia (6; 28.3%) and thrombocytopenia (2; 14.3%) [Table 2]. No fatal events were observed. The median number of cycles received was 5 (range 2 - 13) and 7 (33%) patients received more than 6 cycles. For dose levels 2-3 at cycle 7, a CI was attained in one subject at dose level 2 [anemia, spleen and TSS], 5 subjects had SD, 3 subjects had PD and two subjects with 10% and 15% blasts at screening developed MPN-BP while on study based on central review. Reasons for discontinuation by local PI included PD (n=8), lack of response (n=5), study completed (n=2), other (n=2), patient decision (n=1). Median % change in palpable spleen length was +10% (range -70% to +150%) and TSS change was -50% (-100% to +185.7%) The median platelet count at baseline was 114 x 10 9/L (range: 28-695) and 215 x 10 9/L (range: 66-263) after cycle 6 in 7 evaluable subjects (Fig 2A). Notably, 17 subjects had an increase in platelets from baseline during treatment and two subjects normalized their platelet counts. Maximum changes in platelets from baseline across all cycles was +63.8% [range -15.7%, +505.5%] (Fig 2B). Paired bone marrow biopsy pathology samples for 12 subjects were available for central review and showed no significant changes in BMF score or MK histo topography at end of treatment compared to baseline. All patients had elevated plasma levels of TGF β1, but not TGFβ2/β3 levels as detected by ELISA, which were dramatically reduced 21 days after the last dose of AVID200. AVID200 a TGFβ1/3 protein trap is well tolerated and clinical responses at cycle 7 of therapy in this advanced MF patient population were limited as judged by IWG/MRT response criteria. However, AVID200 therapy resulted in significant reduction in serum TGFβ levels and improvements in platelet counts indicating that TGF β1 plays a pivotal role in MF leading to thrombocytopenia which can be reversed with AVID200 therapy. We conclude that AVID200 may best be employed in combination therapy approaches in thrombocytopenic MF patients. Figure 1 Figure 1. Disclosures Mascarenhas: Constellation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Promedior: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Geron: Consultancy, Research Funding; Forbius: Research Funding; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Galecto: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prelude: Consultancy; Kartos: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Geron: Consultancy; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merus: Research Funding. Palmer: PharmaEssentia: Research Funding; Sierra Oncology: Consultancy, Research Funding; Incyte: Research Funding; CTI BioPharma: Consultancy, Research Funding; Protagonist: Consultancy, Research Funding. Kuykendall: Celgene/BMS: Honoraria; Pharmaessentia: Honoraria; Novartis: Honoraria, Speakers Bureau; Protagonist: Consultancy, Research Funding; Incyte: Consultancy; Abbvie: Honoraria; Blueprint: Honoraria. Mesa: Genentech: Research Funding; Promedior: Research Funding; Samus: Research Funding; Gilead: Research Funding; CTI: Research Funding; Abbvie: Research Funding; Sierra Oncology: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy; Pharma: Consultancy; CTI: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding; AOP: Consultancy; La Jolla Pharma: Consultancy; Incyte Corporation: Consultancy, Research Funding. Rampal: Stemline: Consultancy, Research Funding; Memorial Sloan Kettering: Current Employment; BMS/Celgene: Consultancy; Abbvie: Consultancy; CTI: Consultancy; Novartis: Consultancy; Disc Medicine: Consultancy; Blueprint: Consultancy; Pharmaessentia: Consultancy; Incyte: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Constellation: Research Funding; Kartos: Consultancy; Sierra Oncology: Consultancy. Gerds: PharmaEssentia Corporation: Consultancy; Sierra Oncology: Consultancy; CTI BioPharma: Research Funding; Constellation: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Novartis: Consultancy. Yacoub: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; ACCELERON PHARMA: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dynavex: Current equity holder in publicly-traded company; Cara: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Seattle Genetics: Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Hylapharm: Current equity holder in publicly-traded company. Talpaz: Imago: Consultancy; Constellation: 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; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Other: Grant/research support ; Celgene: Consultancy. Komrokji: Acceleron: Consultancy; Taiho Oncology: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy; Jazz: Consultancy, Speakers Bureau. Kremyanskaya: Astellas: Research Funding; Astex: Research Funding; Chimerix: Research Funding; Bristol Myers Squibb: Research Funding; Constellation: Research Funding; Protagonist Therapeutics: Consultancy, Research Funding; Incyte: Research Funding. Salama: Mayo Clinic: Current Employment, Other: Mayo Clinic had the contractual work for the central pathology review for this study and I was one of the reviewing pathologists; Constellation Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Hoffman: Kartos Therapeutics, Inc.: Research Funding; Protagonist Therapeutics, Inc.: Consultancy; Novartis: Other: Data Safety Monitoring Board, Research Funding; AbbVie Inc.: Other: Data Safety Monitoring Board, Research Funding. OffLabel Disclosure: AVID200 is a TGFb trap and is in clinical testing for fibrotic diseases. It does not have an approved indication at this time.