Abstract: 7573 Background: Black patients have been shown to have a higher incidence of cutaneous T-cell lymphomas (CTCL) and display unique clinicopathologic features at diagnosis, however, drivers of these disparities and the role of social determinants of health (SDoH) remain poorly understood. Methods: To further characterize the prognostic relevance of racial and demographic disparities in CTCL, we performed a retrospective review of 1,198 patients seen at 8 different academic treatment centers in the United States between 2000-2020. Clinical variables included demographics, disease characteristics, and survival. Race and ethnicity were stratified into 2 groups for this analysis: non-Hispanic Black (B) and Non-Black (NB). Distance to center was stratified into short, intermediate, or long commute ( 〈 10, 10-50, 〉 50 miles, respectively) based on home zip code. The primary endpoint was overall survival (OS). Univariate association and multivariable analyses were assessed using Cox proportional hazards models. Results: Among 1,198 total patients, 42.4% identified as B and 58.6% as NB. B patients presented younger, had a shorter commute, lower income, but no difference in insurance compared to NB patients. There was no difference in survival by race (Median OS 74 months (95% CI 65-84) compared to 65 (95% CI 58-75) for NB patients). Distance to center was strongly associated with survival and remained significant on multivariate analyses after controlling for age, race, and other SDoH. Longer commute was associated with worse OS compared to short commute for both B and NB counterparts (median 55 months [95% CI 49-66] vs. 79 [95% CI 69-90] and 75 [95% CI 63-86], respectively, p = 0.006). Conclusions: We characterized the impact of race and SDoH on overall survival (OS) in a diverse, multicenter cohort of patients with CTCL. We found that distance to cancer center was the most important factor contributing to disparities in OS in this study. This highlights the importance of improving access to care, particularly in rare and clinically heterogeneous diseases such as CTCL.

Abstract: Patients with mycosis fungoides have an increased risk for additional malignancies, particularly hematologic malignancies. Of the malignancies that have been associated with mycosis fungoides, renal cell carcinoma and other solid tumor malignancies have not been studied extensively. In this case series, we describe three mycosis fungoides patients who were diagnosed with clear cell renal cell carcinoma and discuss the potential pathophysiology underlying this association.

Abstract: Given that mycosis fungoides−cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT). Objectives To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL. Design, Settings, and Participants This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL. Interventions In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks. Main Outcomes and Measures The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020. Results The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P  = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT ( P   & lt; .001 vs cycle 1 hypericin) and to 49% after 3 cycles ( P   & lt; .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred. Conclusion and Relevance The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile. Trial Registration ClinicalTrials.gov Identifier: NCT02448381

Abstract: Background MAVORIC was a phase 3, open-label, multi-center, randomized controlled trial that evaluated the safety and efficacy of mogamulizumab compared with vorinostat in patients with relapsed/refractory mycosis fungoides (MF) or Sézary syndrome (SS) (NCT01728805). Mogamulizumab-associated rash was the second most common TEAE of any cause or grade in the mogamulizumab treatment arm and the most common TEAE leading to treatment discontinuation, resulting in a discontinuation rate of 7% (13/184). Grade 1-2 and 3 drug rashes occurred in 20% (36/184) and 4% (8/184) of mogamulizumab-treated patients, respectively. The objectives of this analysis were to describe histopathological and other characteristics of drug rash in patients who received mogamulizumab in MAVORIC. Methods In MAVORIC, 372 patients were randomized 1:1 to receive either intravenous mogamulizumab at 1.0 mg/kg once weekly for Cycle 1 (28 days) and then on days 1 and 15 of subsequent cycles or oral vorinostat at 400 mg daily. Confirmed overall response rate (ORR; complete response + partial response) was based on a global composite response involving all four disease compartments and verified at two consecutive visits. Guidance to investigators was provided in the protocol for evaluation and management of new drug rash on mogamulizumab treatment. Patients with an initial Grade 1 drug rash were allowed to continue treatment with use of topical steroids as needed. For patients with Grade ≥2 drug rash, mogamulizumab was temporarily stopped, and treatment of the drug rash with topical steroids was advised. Use of systemic steroids was prohibited during the study. Treatment could resume if the drug rash resolved to Grade ≤1 within 2 weeks. Biopsies were evaluated by an on-site pathologist, and a central blinded review was also conducted. Results This analysis included 44 patients who were treated with mogamulizumab and experienced drug rash during MAVORIC. Pathologically, central review assessed rashes as granulomatous, histiocytic spongiotic, lichenoid, eosinophilic, psoriasiform, or a combination of these patterns with no clear predominant histological pattern. Among the 44 patients with drug rash, 59.1% (26/44) were ≥65 years of age, and more patients with SS [56.8 (25/44)] than MF [43.2% (19/44] ) experienced drug rash. Median (Q1, Q3) exposure among patients with drug rash was 344 days (162, 652) in patients with SS and 185 days (85, 463) in patients with MF. Mogamulizumab did not result in any cases of anaphylaxis or SJS/toxic epidermal necrolysis (TEN). Concomitant or immediate prior CTCL therapies that may make patients prone to drug rash were examined, and no trend toward increased incidence of drug rash was observed with any particular agent or class. The proportion of SS responders with drug rash was significantly higher than responders without rash (P=0.02; Figure 1); the proportion of MF responders with drug rash did not differ from responders without rash (P=0.21). Overall, the median (Q1, Q3) time to onset of drug rash was 106 days (36, 254). Initial drug rash occurred after response to mogamulizumab in 70% (14/20) of patients who experienced both. Thirty-five patients (80%) in the drug rash cohort resumed treatment with mogamulizumab upon resolution of initial drug rash per-protocol. After these patients resumed treatment, the median (Q1, Q3) duration of exposure to mogamulizumab was 183 days (58, 332). Conclusions Mogamulizumab-associated rashes displayed heterogeneous histopathology without one predominant feature; therefore, close correlation of suspected drug rash with clinical features is advised to differentiate it from disease progression. A trend toward higher rate of drug rash was observed in patients with SS, the group more likely to respond to mogamulizumab. Therefore, drug rash may be attributable to increased exposure, but rash may also involve underlying disease characteristics or treatment-induced immune alterations; further investigations are warranted. Nevertheless, the observation that 80% of patients on trial were able to continue mogamulizumab for & gt;6 months following resolution of their initial rash suggests that appropriate evaluation, identification, and management of these reactions may prevent premature discontinuation. Disclosures Musiek: Kyowa Kirin: Honoraria; Helsinn: Honoraria; miRagen: Other: Investigator; Elorac: Other: Investigator; Soligenix: Other: Investigator. Horwitz:ASTEX: Consultancy; Affirmed: Consultancy; Vividion Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Infinity/Verastem: Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Millenium/Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Corvus: Consultancy; Innate Pharma: Consultancy; Mundipharma: Consultancy; Portola: Consultancy, Research Funding; Beigene: Consultancy; C4 Therapeutics: Consultancy; Daiichi Sankyo: Research Funding; GlaxoSmithKline: Consultancy; Janssen: Consultancy; ADCT Therapeutics: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Kura Oncology: Consultancy; Miragen: Consultancy; Myeloid Therapeutics: Consultancy; Aileron: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Bagot:Helsinn/Recordati: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Huen:Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medivir: Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Galderma: Other: Travel expense reimbursement, Research Funding; miRagen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Helsinn: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Research Funding; Rhizen: Consultancy, Research Funding. Fisher:Dana-Farber Cancer Institute: Current Employment; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees. Haun:Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Karger, Inc.: Patents & Royalties: Textbook royalties. Vermeer:Kyowa Kirin: Consultancy, Research Funding; Takeda: Research Funding; PIQUR: Research Funding; Innate Pharma: Consultancy. Ito:Kyowa Kirin Pharmaceutical Development, Inc.: Current Employment. Dwyer:Kyowa Kirin Pharmaceutical Development, Inc.: Current Employment. Herr:Kyowa Kirin, Inc.: Current Employment. Kim:Elorac: Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Corvus: Research Funding; Medivir: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin Pharma: Research Funding; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forty Seven Inc: Research Funding; Galderma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Horizon Pharma: Consultancy, Research Funding; miRagen: Research Funding; Merck: Research Funding; Solingenix: Research Funding; Trillium: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Neumedicine: Consultancy, Research Funding; Portola: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Abstract: Background: Severe thrombocytopenia (TCP) can be a serious complication of chemotherapy (CT) in lymphoma patients (pts), however the exact incidence with the current regimens and risk factors for TCP are not well known. Methods: A retrospective cohort study was conducted to determine the incidence of TCP, and logistic regression analysis were performed to identify the clinical and laboratory features correlated with severe TCP in lymphoma. Medical records of 538 consecutive pts out of the 1050 lymphoma pts, who were newly referred to MDACC in 2003, were reviewed. Results: 202 pts who received & gt; 1 cycle of treatment were included in the analysis. The total number of CT cycles (with PLT counts) for the 202 pts was 985 (median 6, range, 1–20). Grade (gr) 4 TCP (PLT nadir & lt; 25x103/μL) was observed in 39% (79/202) of pts and 20% (196/985) of cycles. The median cycle in which gr 4 TCP occurred was 2 (range, 1 to 11), and median PLT nadir count for gr 4 TCP was 12x103/μL (3 to 24x103/μL). The regimens most commonly associated with gr 4 TCP were Hyper-CVAD/ Ara-c/Mtx (31/35=89%), ESHAP (6/7=86%), ASHAP (3/4=75%), and ICE (5/7=71%) + rituxan, and the most common histological subtypes were MCL (15/19=79%), Burkitts lymphoma (7/9=78%), T cell lymphoma (10/17=58%), and LCL (31/64=48%). Thirty two of 79 (41%) gr 4 TCP pts had bleeding as compared to 8 of 123 (7%) pts with higher PLT counts (p=0.0001). Overall, the incidence of bleeding was 20% (40/202) by pts and 6% (60/985) by cycles; however, the most incidents [95% (57/60)] were minor. 80% (63/79) of Grade 4 TCP pts received PLT transfusions, as compared to only 2% (2/123) of the rest (p & lt;0.0001). Using multivariate logistic regression, histological gr, (highly aggressive or aggressive vs indolent: OR=10.402, 95% CI, 3.991 to 27.107, p & lt;0.0001), baseline PLT count (≤150 vs & gt;150x103/μL: OR=4.610, 95% CI, 1.366 to 15.560, p=0.0138), prior therapy (yes vs. no: OR=2.575, 95% CI, 1.337 to 4.961, p=0.0047), Beta2 Microglobulin (B2M) (≥2 vs & lt;2mg/L: OR=2.846, 95% CI, 1.401 to 5.783, p=0.0038), age ( & gt;60 vs. ≤60 yrs: OR=0.479, 95% CI, 0.241 to 0.952, p=0.0356) were the most important risk factors for grade 3 or 4 TCP. Conclusions: The incidence of severe TCP in this population is high. Baseline pt characteristics including histological gr, PLT counts, prior therapy, age and serum B2M were found to be significant risk factors predictive for chemotherapy-induced TCP (CIT). These findings could be useful to identify high risk pts for consideration of treatment approaches for prevention and treatment of CIT.