Faculty Bibliography

[Formula presented] Background: The interaction between donor killer immunoglobulin-like receptor (KIR) and recipient HLA has been postulated to enhance the graft-versus-leukemia effect in allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). Historically, analyses of individual interactions between single KIR and their respective HLA ligands have yielded conflicting findings, and the clinical importance of these interactions in the matched unrelated donor (MUD) setting remains controversial. Here, we applied a systematic approach, studying both a wide range of KIR and class I HLA interactions at the single-receptor level as well as the most prevalent KIR genotypes in a large cohort of AML patients undergoing MUD transplantation.
Method(s): We included adult AML patients in complete remission transplanted from an 8/8-HLA MUD between 2010 and 2016 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Donor-KIR and respective recipient-HLA ligand interactions were assessed in multivariable Cox proportional hazard models for standard transplantation outcomes. To account for the compound effect of simultaneous KIR/HLA interactions, we applied a combinatorial approach to identify aggregate KIR genotypes based on combinations of individual KIR genes. The most frequently observed donor-KIR genotypes, in combination with recipient ligands, were evaluated for association with relapse using multivariable regression. Those associated (p < 0.01) with relapse risk were evaluated for differential relapse in a DRST (German stem-cell registry)/Collaborative Biobank cohort of donors/patients with similar inclusion criteria.
Result(s): A total of 2,036 transplantations from the CIBMTR were included. Most patients were treated in first complete remission (78%) and received myeloablative conditioning (59%). We first studied eight known interactions between donor KIR and their respective HLA ligands (Figure A). Only donor-KIR-2DL2+/recipient-HLA-C1+ was associated with reduced relapse (compared to donor-KIR-2DL2-/recipient-HLA-C1+, hazard ratio [HR] 0.80 [95% confidence interval 0.67-0.94], p=0.008). However, no difference was found when comparing HLA-C group pairs among KIR-2DL2+ recipients, suggesting this finding is confounded by co-occurrence of other receptors. There are hundreds of possible KIR gene combinations (i.e. genotypes), which are typically clustered into two primary haplotypes, A and B. To study the cumulative effect of donor KIR, we investigated nine prevalent KIR genotypes (Figure B) and identified three significantly associated with relapse risk. (1) Donor KIR genotype 5 in all recipients irrespective of their HLA (Figure C, n = 138/2,036) and (2) genotype 3 in HLA-Bw4/x recipients (Figure D, n = 51/1,198) had significantly decreased relapse risk (HR 0.53 [0.37-0.78], p=0.002 and 0.34 [0.15-0.75], p=0.008, respectively). (3) KIR genotype 2 was associated with greater relapse in HLA-C1-homozygous recipients (Figure E, n = 87/836, HR 1.62 [1.14-2.30], p=0.007). These findings were not confirmed in the external European dataset (n = 796, Figure 1C-E); however, this cohort differed in ways that might affect the importance of KIRs, such as the higher frequency of reduced intensity conditioning (74% vs. 41%) and in-vivo T-cell depletion (79% vs. 37%).
Conclusion(s): Our systematic investigation in two large AML cohorts receiving MUD allogenic HCT did not validate any association between individual KIR-HLA interactions and clinical outcomes. A combinatorial approach identified combinations potentially protective against relapse, however these could not be confirmed in a second dataset. Overall, our findings do not support KIR-informed donor selection using the approaches outlined here. [Formula presented] Disclosures: Shouval: Medexus: Consultancy. Kroeger: AOP Pharma: Honoraria; Gilead/Kite: Honoraria; Riemser: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria. Horowitz: Daiicho Sankyo: Research Funding; Allovir: Consultancy; Miltenyi Biotech: Research Funding; Medac: Research Funding; Kite/Gilead: Research Funding; Genentech: Research Funding; Jazz Pharmaceuticals: Research Funding; Janssen: Research Funding; Kiadis: Research Funding; CSL Behring: Research Funding; Gamida Cell: Research Funding; bluebird bio: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; Astellas: Research Funding; Chimerix: Research Funding; GlaxoSmithKline: Research Funding; Novartis: Research Funding; Magenta: Consultancy, Research Funding; Actinium: Research Funding; Mesoblast: Research Funding; Omeros: Research Funding; Orca Biosystems: Research Funding; Pfizer, Inc: Research Funding; Pharmacyclics: Research Funding; Regeneron: Research Funding; Sanofi: Research Funding; Seattle Genetics: Research Funding; Shire: Research Funding; Sobi: Research Funding; Stemcyte: Research Funding; Takeda: Research Funding; Tscan: Research Funding; Vertex: Research Funding; Vor Biopharma: Research Funding; Xenikos: Research Funding. Malmberg: Merck: Research Funding; Vycellix: Consultancy; Fate Therapeutics: Consultancy, Research Funding. Miller: Sanofi: Membership on an entity's Board of Directors or advisory committees; Magenta: Membership on an entity's Board of Directors or advisory committees; ONK Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Vycellix: Consultancy; GT Biopharma: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics, Inc: Consultancy, Patents & Royalties, Research Funding; Wugen: Membership on an entity's Board of Directors or advisory committees. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria. Romee: Crispr Therapeutics: Research Funding; Glycostem: Membership on an entity's Board of Directors or advisory committees. Schetelig: Roche: Honoraria, Other: lecture fees; Novartis: Honoraria, Other: lecture fees; BMS: Honoraria, Other: lecture fees; Abbvie: Honoraria, Other: lecture fees; AstraZeneca: Honoraria, Other: lecture fees; Gilead: Honoraria, Other: lecture fees; Janssen: Honoraria, Other: lecture fees. Weisdorf: Fate Therapeutics: Research Funding; Incyte: Research Funding. Koreth: Biolojic Design: Other: Scientific Advisory Board; Mallinckrodt: Other: Scientific Advisory Board; Cugene: Other: Scientific Advisory Board; Moderna: Consultancy; Amgen: Consultancy; EMD Serono/Merck: Consultancy; Gentibio Inc.: Consultancy; Miltenyi Biotec: Research Funding; BMS: Research Funding; Clinigen Labs: Research Funding; Regeneron: Research Funding; Equillium: Research Funding.
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BACKGROUND:The association between isotretinoin and psychiatric disturbance, including depression and suicidal behavior, is controversial. OBJECTIVE:To investigate whether acne patients prescribed isotretinoin or antibiotics were more likely to have psychiatric disorders and/or engage in suicidal behavior. METHODS:Retrospective cohort study identified acne patients prescribed isotretinoin or oral antibiotics in the IBM® MarketScan® Databases of commercial US insurance claims data from 2011-2017 who were also diagnosed with psychiatric disorders or suicidal behavior. RESULTS:A total of 72,555 patients were included. Compared to acne patients prescribed isotretinoin, patients in the general population were 1.47 times more likely to be diagnosed with suicidal ideation or attempt (adjusted OR 1.47; 1.27, 1.70, p <.0001). However, the general population (adjusted OR 0.87; 0.84, 0.89, p<0.0001) and acne patients prescribed antibiotics (adjusted OR 0.88; 0.85, 0.91, p<0.0001) were less likely to have a psychiatric diagnosis compared to acne patients prescribed isotretinoin. The prevalence of suicidal behavior during isotretinoin treatment was lower (0.10%) (p=0.082), than during the year prior to (0.22%) and during the year after isotretinoin treatment (0.34%), (p = 0.004). LIMITATIONS/CONCLUSIONS:Study excludes individuals with public or no insurance and relies on physician coding accuracy. CONCLUSIONS:Compared to the general population, acne patients prescribed isotretinoin were less likely to engage in suicidal behavior. Further exploration is warranted into the slight increase in suicidal behavior seen in isotretinoin patients one year after therapy.

COVID-19 RT-PCR employee-testing was implemented across NYU Langone. Over eight-weeks, 14,764 employees were tested: 33% of symptomatic employees, 8% of asymptomatic employees reporting COVID-19 exposure, 3% of employees returning to work were positive. Positivity rates declined over time possibly reflecting the importance of community transmission and efficacy of PPE.

BACKGROUND/OBJECTIVE/OBJECTIVE:Papular scars are a recently described clinical phenotype of acne scarring characterized by papules occurring on the nose and chin. We have observed a similar presentation of nasal papules among patients seen in our clinic for acne and sought to further characterize the clinical and histopathological characteristics of this entity. METHODS:In this single-site case series, a retrospective review of electronic medical records of patients with nasal papules in association with acne vulgaris between April 2018 and April 2019 was performed. Clinical and histopathologic findings were recorded. RESULTS:We identified 20 patients who presented with a similar clinical phenotype of predominantly skin-colored, dome-shaped papules concentrated on the nose and chin in association with a history of more classic facial acne vulgaris. Papular lesions were seen predominately in adolescent Hispanic males. Concomitant acne on other areas of the face was identified in 18 patients at presentation while two patients had a history of adolescent acne. Biopsies were performed for five patients. Histopathologic examination demonstrated features of fibrosis and dilated thin-walled blood vessels, typical of angiofibromas. CONCLUSION/CONCLUSIONS:We present a series of adolescent patients with large, flesh-colored to erythematous papules seen predominantly on the nose. These lesions are histologically indistinguishable from angiofibromas and may represent an under-recognized yet disfiguring sequela of acne that may disproportionately affect adolescents with skin of color.

We conducted a phase I-II study to evaluate Nilotinib (NIL) safety and pharmacokinetics in 22 SR-cGVHD patients; we also evaluated ORR by using in parallel NIH criteria and an exploratory approach, combining objective improvement (OI) without failure criteria (GITMO criteria). Results: 22 patients were enrolled. After dose escalation up to 600 mg/day, MTD was not reached. Main toxicities were asthenia, headache, nausea, pruritus, cramps, and mild anemia. Mean and median plasma concentrations of NIL (C-NIL) were 817 (SD ± 450) and 773 ng/ml. ORR at 6 months, according to 2005 and 2014 NIH and GITMO criteria were 27.8%, 22.2%, and 55.6% respectively; close correspondence has been observed for ORR, according to 2014 NIH criteria, both assessed in a conventional way and assisted by dedicated software (CROSY). At 48 months OS was 75% while FFS, according to NIH and GITMO criteria, was 30 and 25%. In conclusion the safety profile of NIL and long-term outcome makes NIL an attractive option in SR-cGVHD. Exploratory GITMO criteria could represent an alternative tool for easy response evaluation in patients with prevalent skin and lung involvement, but require validation in a larger population; CROSY software showed excellent reliability in capturing ORR according to the 2014 NIH criteria.