Cutaneous T-cell Lymphoma Research Articles

Preliminary Experience in Ultra-High Frequency Ultrasound Assessment of Cutaneous Primary Lymphomas: An Innovative Classification.

Primary cutaneous lymphoma (PCL) is a rare form of extranodal non-Hodgkin's lymphoma characterized by malignant lymphocytes confined to the skin. Accurate diagnosis and staging are crucial for optimal management, yet radiological literature on imaging PCL remains limited. This study aims to delineate the imaging characteristics of PCLs using high and ultra-high frequency ultrasound (UHFUS) and proposes a classification system based on ultrasound findings. A cohort of 88 individuals with suspected PCL underwent high-resolution ultrasound (HRUS) and color Doppler examination of lesions. Lesions were categorized based on sonographic appearance, and subsequent histopathological assessment confirmed the diagnosis. Ultrasound imaging revealed distinct patterns for primary cutaneous T-cell lymphomas (PCTCL) and primary cutaneous B-cell lymphomas (PCBCL), with characteristic features such as hypoechoic nodules, pseudonodular lesions, and dermal infiltration. Histopathological analysis confirmed the ultrasound findings, supporting the proposed classification system. Ultrasonography, particularly UHFUS, offers valuable insights into the imaging characteristics of primary cutaneous lymphomas, aiding the accurate diagnosis and assessment of treatment response. The proposed classification system based on ultrasound findings enhances the diagnostic approach to PCLs, and paves the way for improved patient care and management strategies.

Role of extracorporeal photopheresis in the management of acute and chronic graft versus disease: current status.

Extracorporeal photopheresis (ECP) is a therapy that combines the collection of mononuclear cells by apheresis, the addition of a photosensitizer (8-methoxisoralen), the illumination of the product with ultraviolet A light, and the immediate infusion of the product to the patient. Initially developed and approved to treat T-cell cutaneous lymphomas, soon started to be used to treat graft versus host disease (GvHD) developed after allogeneic hematopoietic-cell transplantation. The high response rate of ECP in skin, ocular, oral, pulmonary, and liver forms of chronic GvHD, the steroid-sparing effect, and the improved overall survival of treated patients, made ECP one of the second-line treatments used to treat steroid-resistant acute and chronic GVHD. Recently, the development of new drugs for treating GVHD has changed the position of ECP in the therapy of GVHD and has started to be used in combination with drugs for increasing the response rate to the treatment in severe or resistant forms of acute and chronic GVHD. ECP remains an essential therapeutic resource in the management of patients with refractory acute and chronic GVHD.

Cantharidin overcomes IL-2Rα signaling-mediated vorinostat resistance in cutaneous T-cell lymphoma through reactive oxygen species

BackgroundVorinostat (SAHA) is a histone deacetylase inhibitor that has shown clinical efficacy against advanced cutaneous T-cell lymphoma (CTCL). However, only a subset of patients with CTCL (30–35%) respond to SAHA...

Delays in diagnosis in cutaneous T-cell lymphoma: A retrospective study on clinical course and time to death

Delays in diagnosis in cutaneous T-cell lymphoma: A retrospective study on clinical course and time to death

Breaking the Vicious Cycle of Staphylococcal aureus Skin Colonization and Progression of Cutaneous T-Cell Lymphoma

Breaking the Vicious Cycle of Staphylococcal aureus Skin Colonization and Progression of Cutaneous T-Cell Lymphoma

Metabolomics analyses reveal the crucial role of ERK in regulating metabolic pathways associated with the proliferation of human cutaneous T-cell lymphoma cells treated with Glabridin.

Cutaneous T-cell lymphomas (CTC) are a heterogeneous group of T-cell lymphoproliferative malignancies of the skin with limited treatment options, increased resistance and remission. Metabolic reprogramming is vital in orchestrating the uncontrolled growth and proliferation of cancer cells. Importantly, deregulated signalling plays a significant role in metabolic reprogramming. Considering the crucial role of metabolic reprogramming in cancer-cell growth and proliferation, target identification and the development of novel and multi-targeting agents are imperative. The present study explores the underlying mechanisms and metabolic signalling pathways associated with Glabridin mediated anti-cancer actions in CTCL. Our results show that Glabridin significantly inhibits the growth of CTCL cells through induction of programmed cell death (PCD) such as apoptosis, autophagy and necrosis. Interestingly, results further show that Glabridin induces PCD in CTCL cells by targeting MAPK signalling pathways, particularly the activation of ERK. Further, Glabridin also sensitized CTCL cells to the anti-cancer drug, bortezomib. Importantly, LC-MS-based metabolomics analyses further showed that Glabridin targeted multiple metabolites and metabolic pathways intricately involved in cancer cell growth and proliferation in an ERK-dependent fashion. Overall, our findings revealed that Glabridin induces PCD and attenuates the expression of regulatory proteins and metabolites involved in orchestrating the uncontrolled proliferation of CTCL cells through ERK activation. Therefore, Glabridin possesses important features of an ideal anti-cancer agent.

Oncogenic alterations in KIR3DL1 in cutaneous acral CD8+ lymphoproliferative disorder.

Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder (TLPD) is a rare and indolent lymphoma entity. Although TLPD was first identified many years ago, the molecular pathogenesis is still not fully understood. In order to better understand the molecular pathogenesis of cutaneous acral CD8+ TLPD and to identify further discriminatory markers to differentiate this lymphoma subtype from other CD8+ cutaneous lymphomas, we analysed five cases of cutaneous acral CD8+ TLPD for putative molecular alterations. Somatic alterations were assessed using whole-exome and targeted sequencing of paraffin-embedded tissue. Results were evaluated using immunohistochemical staining of respective relevant proteins. CD8+ cutaneous T-cell lymphomas (n = 12) served as control for KIR3DL1 staining. Copy number variation analysis revealed a homozygous deletion of the KIR3DL1 gene in two of the analysed cases. This resulted in loss of KIR3DL1 protein expression, which was observed in all cases of cutaneous acral CD8+ TLPD. In contrast, KIR3DL1 expression was more variable in other CD8+ cutaneous T-cell lymphomas with 50% of analysed cases (n = 12) found to be positive. In addition, one further case of acral CD8+ TLPD harboured a loss-of-function mutation in the PIK3R1 gene, presumably activating the phosphoinositide 3-kinase-AKT pathway. Alterations of the KIR3DL1 gene may be of pathogenetic relevance for acral CD8+ TLPD. Loss of KIR3DL1 protein expression may support the diagnosis of this indolent lymphoma entity; however, this is not a subtype-specific discriminative feature.

Cutaneous Lymphoma in a Tertiary Skin Hospital and Referral Centre in Nepal.

Primary cutaneous lymphomas are a distinct group of rare lymphoid neoplasms with absence of extracutaneous lymphomas at the time of presentation. They are rare in Nepal and no data on cutaneous lymphoma have been published from this country till date. This retrospective study included 15 cases of cutaneous lymphomas retrieved from the records of department of Dermatopathology, DI Skin Hospital and Referral Centre, Bansbari, Kathmandu, Nepal. Patients were diagnosed according to the current WHO classification for cutaneous lymphoma. A total of 15 cases were studied with median age of 45 years (range: 22 to 81 years) and male to female ratio of 1.5:1. Primary cutaneous lymphomas constituted 13 cases out of 15 and the most common type of cutaneous lymphoma was mycosis fungoides and variants 5 (33%), followed by CD30 positive primary cutaneous anaplastic large cell lymphoma constituting 2 (13%). T-cell cutaneous lymphoma constituted 13 (87%) and B-cell cutaneous lymphoma 2 (13%). Cutaneous T-cell lymphomas were more frequent than cutaneous B-cell lymphomas in Nepalese patients. Mycosis fungoides and variants are commonest type of primary cutaneous lymphomas.

Real-life efficacy of immunotherapy for Sézary syndrome: a multicenter observational cohort study

Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61-79): 33 pre-Sézary (9.7% of 339), 296Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53-68). OS was 46.5% (95% CI, 40.6%-53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus <50 (HR: 4.9, 95% CI, 2.1-11.2, p=0.001), and large-cell transformation (HR: 2.8, 95% CI, 1.6-5.1, p=0.001) were independent and significant factors associated with reduced OS. Mogamulizumab treatment was significantly associated with decreased mortality (HR: 0.34, 95% CI, 0.15-0.80, p=0.013). Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.

Morphoea presenting histopathologically as mycosis fungoides: an illustrative series of four cases.

There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous Tcell lymphoma of the mycosis fungoides type (MF). This phenomenon gives rise to an ambiguous clinicopathological scenario in which distinguishing these conditions may be challenging. The aim of this study is to characterise the clinical, histopathological and molecular findings of this phenomenon through a case series. Four patients with classical clinical presentation of morphoea but unusual histopathology displaying typical findings of morphoea, together with intra-epidermal CD8 positive lymphocytes indistinguishable from MF, were identified. The clinical phenotypes of morphoea were varied, and they all presented early in the active phase of the disease. They all exhibited intra-epidermal lymphocytes with tagging and cytological atypia. Pautrier-like microabscesses were also seen. Using molecular analysis, two cases showed clonal TCR gene rearrangement. Follow-up of all cases has been consistent with classical morphoea. Early morphoea can seldom present with atypical clonal intra-epidermal lymphocytes indistinguishable from MF. The fact that these changes can occur in several different clinical subtypes of morphoea raises the possibility that this could be a pattern of inflammation in early disease more common than currently appreciated.

LAIR1 prevents excess inflammatory tissue damage in S. aureus skin infection and Cutaneous T-cell Lymphoma.

Patients with cutaneous T cell lymphoma (CTCL) experience high morbidity and mortality due to S. aureus skin infections and sepsis, but the causative immune defect is unclear. We previously identified high levels of LAIR2, a decoy protein for the inhibitory receptor LAIR1, in advanced CTCL. Mice do not have a LAIR2 homolog, so we used Lair1 knock-out (KO) mice to model LAIR2 overexpression. In a model of subcutaneous S. aureus skin infection, Lair1 KO mice had significantly larger abscesses and areas of dermonecrosis compared to WT. Lair1 KO exhibited a pattern of increased inflammatory responses in infection and sterile immune stimulation, including increased production of proinflammatory cytokines and myeloid chemokines, neutrophil ROS, and collagen/ECM remodeling pathways. Notably, Lair1 KO infected skin had a similar bacterial burden and neutrophils and monocytes had equivalent S. aureus phagocytosis compared to WT. These findings support a model in which lack of LAIR1 signaling causes an excessive inflammatory response that does not improve infection control. CTCL skin lesions harbored similar patterns of increased expression in cytokine and collagen/ECM remodeling pathways, suggesting that high levels of LAIR2 in CTCL recapitulates Lair1 KO, causing inflammatory tissue damage and compromising host defense against S. aureus infection.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.

Updated cutaneous T-cell lymphoma TNMB staging criteria fail to identify patients with Sézary syndrome with low blood burden

Comparison of the 2007 EORTC/ISCL and the 2022 EORTC/ISCL/USCLC blood staging guidelines for cutaneous T-cell lymphoma at a single institution reveals the newer guidelines fail to detect a subset of Sézary syndrome patients with low blood burden.

Chart review study of real-world clinical outcomes in patients with cutaneous T-cell lymphoma treated with extracorporeal photopheresis in the US in 2017–2019

Background Response rates of approved systemic therapies for cutaneous T-cell lymphoma (CTCL) hover near 30%, suggesting unmet need. This study describes real-world treatment patterns and response rates of extracorporeal photopheresis (ECP) in CTCL patients. Methods A chart review was conducted in the United States of adults with CTCL who initiated ECP between January 1, 2017, and February 28, 2019, and received at least three months of ECP treatment as monotherapy or concomitant therapy. Clinical outcomes were collected quarterly for up to 18 months. Results The 52 patients were predominantly Caucasian. Half were male; median age was 69 years. Most patients had Sézary syndrome (50%) or mycosis fungoides (36.5%). Nearly 40% of patients had stage IV disease; 33% had lymph node involvement. Nineteen patients (36.5%) achieved response (>50% reduction in BSA affected); median time to response was 6.5 months. The percentage of patients rated as at least minimally improved was 59.5% at 6 months (N = 22), 75.0% at 9 months (N = 24), and 60.0% at 12 months (N = 15) after ECP initiation. Conclusions Despite the ECP treated population in this study being older and having more advanced-stage disease than recent trials, response rates were comparable. These real-world findings support ECP as an effective treatment option for CTCL patients.

Estimation of the tissue and serum levels of IL-35 in Mycosis fungoides: a case-control study

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) with its etiology not yet fully understood. Interleukin (IL)-35 is an inhibitory cytokine that belongs to the IL-12 family. Elevated IL-35 in the plasma and the tumor microenvironment increases tumorigenesis and indicates poor prognosis in different types of malignancies. The objective of this study is to estimate the expression levels of IL-35 in tissue and serum of MF patients versus healthy controls. This case-control study included 35 patients with patch, plaque, and tumor MF as well as 30 healthy controls. Patients were fully assessed, and serum samples and lesional skin biopsies were taken prior to starting treatment. The IL-35 levels were measured in both serum and tissue biopsies by ELISA technique. Both tissue and serum IL-35 levels were significantly higher in MF patients than in controls (P < 0.001) and tissue IL-35 was significantly higher than serum IL-35 in MF patients (P < 0.001). Tissue IL-35 was significantly higher in female patients and patients with recurrent MF compared to male patients and those without recurrent disease (P < 0.001). Since both tissue and serum IL-35 levels are increased in MF, IL-35 is suggested to have a possible role in MF pathogenesis. IL-35 can be a useful diagnostic marker for MF. Tissue IL-35 can also be an indicator of disease recurrence.

Safety and effectiveness of mogamulizumab in relapsed or refractory CC chemokine receptor 4-positive peripheral T-cell lymphoma and relapsed or refractory cutaneous T-cell lymphoma: A post-marketing surveillance in Japan.

Mogamulizumab is a humanized antibody targeting CC chemokine receptor 4 (CCR4). This post-marketing surveillance was conducted in Japan as a regulatory requirement from 2014 to 2020 to ensure the safety and effectiveness of mogamulizumab in patients with relapsed or refractory (r/r) CCR4-positive peripheral T-cell lymphoma (PTCL) or r/r cutaneous T-cell lymphoma (CTCL). Safety and effectiveness data were collected for up to 31weeks after treatment initiation. A total of 142 patients were registered; safety was evaluated in 136 patients. The median number of doses was 8.0 (range, 1-18). The main reasons for treatment termination were insufficient response (22.1%) and adverse events (13.2%). The frequency of any grade adverse drug reaction was 57.4%, including skin disorders (26.5%), infections and immune system disorders (16.2%), and infusion-related reactions (13.2%). Graft-versus-host disease, grade 2, developed in one of two patients who underwent allogeneic-hematopoietic stem cell transplantation after receiving mogamulizumab. Effectiveness was evaluated in 131 patients (103 with PTCL; 28 with CTCL). The best overall response rate was 45.8% (PTCL, 47.6%; CTCL, 39.3%). At week 31, the survival rate was 69.0% (95% confidence interval, 59.8%-76.5%) [PTCL, 64.4% (54.0%-73.0%); CTCL, 90.5% (67.0%-97.5%)]. Safety and effectiveness were comparable between patients <70 and≥70years old and between those with relapsed and refractory disease. The safety and effectiveness of mogamulizumab for PTCL and CTCL in the real world were comparable with the data reported in previous clinical trials. Clinical Trial Registration.

Preliminary validation of a novel patient-reported outcomes (PRO) questionnaire for patients with cutaneous T-cell lymphoma: The CTCL-PRO-18.

e23161 Background: Improving quality of life (QoL) is key to clinical decision-making for patients with cutaneous T-cell lymphoma (CTCL). Currently there is no measure of QoL that captures concerns of patients with advanced-stage CTCL. A thematic analysis of interviews with early- and late-stage patients with CTCL identified novel QoL domains. Using these data, we developed questionnaire items for a new QoL measure (CTCL-PRO-18). Methods: Consented patients completed our new survey and previously validated metrics: SF-36, MF/SS-CTCL QoL, VAS-Itch (past 24 hours), Skindex-29, CES-D, and PROMIS™ Sleep Disturbance. Principal component analysis (PCA) with varimax rotation reduced the number of items on our measure; Cronbach’s alpha evaluated the internal-consistency reliability of items that loaded on each component and the overall measure. We examined the construct and convergent validity of the CTCL-PRO-18 using Pearson correlations, and differences in QoL outcomes by patient demographics and disease status using analyses of variance (ANOVA). Results: 82 patients (47 male; 69 white, 11 Black, 2 Hispanic) completed the surveys. The PCA yielded an 18-item, 5-component solution: 6-item self-consciousness; 3-item burden of treatment; 3-item concern about sores; 3-item sleep/fatigue; and 3-item lack of available CTCL resources. The 5 subscales and overall CTCL-PRO-18 measure had acceptably high reliabilities; Cronbach’s alphas ranged from .74 to .93. Correlations between the CTCL-PRO-18 and each of the previously validated measures were statistically significant (P &lt; .005). Correlations between CTCL-PRO-18 and SF-36 (subscales ranged r =-.320 to -.624), CESD ( r= .645), PROMIS™ Sleep Disturbance ( r= .4780), and VAS-Itch ( r= .665) were moderate. Correlations between CTCL-PRO-18 and MF/SS-CTCL QoL ( r= .720) and Skindex-29 ( r= .814) were high. Correlations between the overall CTCL-PRO-18 and each of its subscales were significant (P &lt; .001) and ranged from .571 (Burden of Treatment) to .882 (Self-consciousness). ANOVAs showed no statistically significant gender or racial/ethnic (white vs. Black/Hispanic race/ethnicity) differences in the CTCL-PRO-18 or the 5 component scores. Burden of Treatment scores were significantly lower for patients with no active disease compared with patients with reduced symptoms and active disease (4.9 [SD 3.9], 6.4 [3.2], and 8.2 [3.8], respectively; P = .018). Conclusions: The CTCL-PRO-18 and its 5 subscales had high internal-consistency reliability. Correlations were higher between the CTCL-PRO-18 and other CTCL-relevant measures (Skindex-29, MF/SS-CTCL QoL) than they were between the CTCL-PRO-18 and less CTCL-specific measures, providing preliminary evidence of the construct and convergent validity of the CTCL-PRO-18. Examination of the discriminant validity of this metric is warranted.

Racial differences in therapies received by patients with cutaneous T cell lymphoma (CTCL): A single center retrospective cohort analysis.

e23141 Background: Black patients with cutaneous T-cell lymphoma (CTCL) have increased risk of mortality and higher rates of treatment complications compared to other racial groups, however, drivers of these disparities are poorly understood. Recent advances in novel targeted therapies, such as mogamulizumab and brentuximab vedotin (BV), have demonstrated improved survival compared to standard therapies. We aimed to identify treatment patterns and clinical outcomes in patients with mycosis fungoides and Sezary syndrome (MF/SS) to better understand potential drivers underlying these racial disparities. Methods: We performed a retrospective review of 282 patients with a histopathologic diagnosis of advanced stage MF/SS seen at the Winship Cancer Institute of Emory University from 2000-2023. Clinical data was collected from the electronic medical record and included demographics, histopathologic findings, therapies received, highest disease stage reached, and survival. Differences in baseline characteristics and treatments were assessed using univariate analysis. The association between race, insurance status, disease stage, and category of treatment was assessed using multivariable analysis of overall survival (OS). Results: The cohort was comprised of an even distribution of patients identifying as Black (50%) and white (47.5%). Median age at diagnosis was 61 years (range, 12-91), and Black patients had an earlier age of diagnosis compared to white (median 52 vs. 65.5 years, p &lt; 0.001). The majority of patients had a pathological diagnosis of MF (79.1%). Large cell transformation was seen in 24.8%. Most common stage was stage 2b (36.2%); other stages included 3a (18.1%), 3b (4.3%), 4a1 (19.1%), 4a2 (13.1%), and 4b (9.2%). Systemic therapies were divided into three groups: standard chemotherapy, biologics (interferon, retinoids, extracorporeal photopheresis, and methotrexate), and novel agents (mogamulizumab, BV, and clinical trials). Median OS was 47.5 months (range, 2-246 months), and was greater in patients who received treatment with novel agents (hazard ratio 0.46, 95%, CI 0.29-0.73, p &lt; 0.001). Black patients were less likely to receive photopheresis and local radiation compared to white patients (36.73% vs. 63.27% and 39.53% vs. 60.47%, p &lt; 0.05, respectively), however, there were no differences in the receipt of novel agents by race. There were no differences in OS between Black and white patients. Conclusions: While we did find some differences in treatment patterns by race, these did not translate to a difference in outcomes. Importantly, in this cohort of patients who received similar rates of novel targeted therapies across racial groups, there were no differences in survival by race. These findings suggest that factors such as access to novel targeted therapies may play a role in the well-documented racial disparities in treatment outcomes.

Effects of Body Mass Index on Hypertriglyceridemia Associated with Oral Bexarotene Therapy: A Post Hoc Analysis of an Open-Label Comparative Clinical Study of Combined Bexarotene and Phototherapy Versus Bexarotene Monotherapy for Japanese Patients with Cutaneous T-Cell Lymphoma.

Bexarotene, which has been approved for use in Japan since 2016, is an effective drug for cutaneous T-cell lymphoma; however, careful management is imperative because of its adverse events. We previously demonstrated the severity of bexarotene-associated hypertriglyceridemia and the need for bexarotene dose reduction for patients with cutaneous T-cell lymphoma and high body mass index (BMI); however, high BMI does not affect the efficacy of combined bexarotene and phototherapy treatment. This study aimed to verify the effects of BMI on hypertriglyceridemia associated with oral bexarotene therapy. We conducted a post hoc analysis of data from a previous randomized, open-label clinical study that compared combined bexarotene-phototherapy treatment with bexarotene monotherapy for cutaneous T-cell lymphoma by dividing patients into two groups based on BMI (<23 kg/m2 and ≥23 kg/m2). No statistically significant association was observed between patients with BMI ≥23 kg/m2 and severe hypertriglyceridemia; however, there was a significant association between BMI ≥23 kg/m2 and severe hypertriglyceridemia for patients who received bexarotene monotherapy, but not for those who received combined bexarotene-phototherapy treatment. The exact reasons for the discrepancies between the results of this thorough analysis and those of our past research are unclear. However, high BMI may be a risk factor for hypertriglyceridemia. Additional unidentified risk factors could also affect treatment outcomes. High BMI is the primary reason for hypertriglyceridemia-associated bexarotene dose reduction; however, unexplored risk factors other than high BMI could exist.

Lacutamab in patients with relapsed and/or refractory mycosis fungoides: Results from the TELLOMAK phase 2 trial.

7082 Background: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-hodgkin’s lymphoma. The most common type of CTCL is Mycosis Fungoides (MF) accounting for 50-60% of cases, while Sezary Syndrome, the leukemic variant of MF accounts for 2-5% of cases. Extracutaneous involvement occurs mainly in lymph nodes or blood; 25% of patients (pts) are diagnosed at advanced stage with a 5-year survival of 15-25%. KIR3DL2 is a killer immunoglobulin-like receptor, expressed in 90% of SS pts, and 50% of MF pts. Lacutamab is a first-in-class monoclonal antibody designed to specifically deplete KIR3DL2-expressing cells via antibody-dependent cell-cytotoxicity and phagocytosis. Methods: TELLOMAK is an international, open-label, multi-cohort phase 2 trial (NCT03902184). MF pts who had received at least 2 prior systemic therapies were allocated to different cohorts according to KIR3DL2 expression in skin. Lacutamab 750 mg is administered as an intravenous infusion until disease progression or unacceptable toxicity. Primary endpoint was Objective Response Rate (ORR) by global response score based on the evaluation of 4 compartments: skin, blood, lymph nodes and viscera according to International Consensus criteria (Olsen 2011; sensitivity analysis vs revised Olsen 2022). Secondary endpoints included other efficacy endpoints, safety, and quality of life. Here we report data of all MF patients, and according to KIR3DL2 status. Results: At the data cutoff of October 13, 2023, recruitment was completed, with 107 pts enrolled. Median age was 62 years. Median number of previous systemic lines was 4 (range: 1-14). Median follow-up was 11.8 months (m) (95% CI 9.9-13.8). ORR was 16.8% (CI 10.9, 25.0; Olsen 2011), and 22.4% (CI 15.6, 31.2; Olsen 2022), response in skin and blood was 29.0% (CI 21.2, 38.2) and 40.0% (CI 24.6, 57.7) respectively. Median time to response was 1.0 months and median PFS 10.2m (CI 6.5, 16.8). Among the KIR3DL2 ≥1% pts (N=48), ORR was 20.8% (CI 11.7,34.3; Olsen 2011), and 29.2% (CI 18.2, 43.2; Olsen 2022), response in skin and in blood was observed in 33.3% (CI 21.7, 47.5) and 41.2% (CI 21.6, 64.0) respectively. Median time to response was 1.0 month and median PFS was 12.0 m (CI 5.6, 20.0). Median duration of response was not reached. Grade ≥ 3 Treatment-related (TR) Treatment-Emergent Adverse events (TEAEs) were observed in 4/107 (3.7%) pts, serious TR TEAEs were observed in 4/107 (3.7%) pts and 3/107 (2.8%) pts discontinued study drug due to TR TEAEs. The most common (&gt;10%) TR TEAEs were fatigue (11.2%), nausea (11.2%), asthenia (10.3%), and arthralgia (10.3%). Conclusions: The data from the heavily pre-treated MF population enrolled to the TELLOMAK study confirms promising clinical activity of lacutamab regardless of KIR3DL2 expression, with a favorable safety and tolerability profile. These data support the further development of lacutamab in an effort to bring improved treatments to patients with CTCL. Clinical trial information: NCT03902184 .