Dermatologic adverse events associated with IDH inhibitors ivosidenib and enasidenib for the treatment of acute myeloid leukemia.

Two novel inhibitors of isocitrate dehydrogenase (IDHi), ivosidenib and enasidenib, significantly improve survival for AML patients with an IDH1 or IDH2 mutation, respectively; however, rash has been reported as a toxicity of IDHi. The objective of our study is to determine the incidence, grade, clinical, and histopathologic features of dermatologic adverse events (DAEs) secondary to IDHi. This study is a retrospective analysis of 169 patients who were treated with either ivosidenib or enasidenib as single agent or in combination with induction chemotherapy at Memorial Sloan Kettering Cancer Center from January 1, 2013 to April 1, 2021. DAEs thought to be possibly, probably, or definitely related to IDHi occurred in 55 of 169 patients [0.32, 95 % CI: 0.25 - 0.40]. Of a total 81 DAEs observed, the most common DAE types were inflammatory dermatoses (27 %); cutaneous vascular manifestations (8%); cutaneous infections (7%); and pruritus (2%). Notably, 50% of infections and 15.5% of rashes were high grade. Knowledge of these findings is critical to optimize the treatment and quality of life of patients with AML on IDHi.

Real-Time Reflectance Confocal Microscopy of Cutaneous Graft-versus-Host Disease Correlates with Histopathology.

Reflectance confocal microscopy (RCM) allows noninvasive, real-time evaluation of the skin at a resolution akin to histopathology (HP), but its application in cutaneous graft-versus-host disease (GVHD) has not been extensively assessed. We describe RCM features of cutaneous GVHD including acute (aGVHD), late acute, chronic (cGVHD; sclerotic and nonsclerotic subtypes), and inactive GVHD and correlate RCM with same-site HP for a subset of patients. Thirty-two adult and pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients with cutaneous GVHD received RCM imaging of ≥1 lesions (n = 44), 13 of which necessitated skin biopsy. RCM images were deidentified and assessed by 2 RCM experts blinded to clinical and HP findings to reach a consensus on the features and patterns of the inflammatory dermatoses. Major RCM features (present in ≥65% of lesional sites) and patterns were reported. To determine the correlation between RCM and HP, detection of cellular features and patterns of inflammatory dermatoses were compared using percent agreement and prevalence-adjusted, bias-adjusted kappa estimates. Seven patients with early or late aGVHD (7 lesions) had irregular honeycombing, spongiosis, dermoepidermal junction (DEJ) and dermal inflammation, and melanophages; those with early aGVHD also had hyperkeratosis, dilated vessels, and coarse connective tissue. Both groups had an interface dermatitis pattern. Eighteen patients with nonsclerotic cGVHD (24 lesions) had irregular honeycombing, spongiosis, DEJ and dermal inflammation, dilated vessels, coarse connective tissue, and interface and spongiotic dermatitis patterns. Three sclerotic patients with cGVHD (7 lesions) had irregular honeycombing, DEJ and dermal inflammation with an interface dermatitis pattern. Four patients with inactive GVHD (6 lesions) showed minimal inflammation. RCM and HP had similar detection rates for 6 of 13 features and overall patterns important for diagnosis in 2 patients with late aGVHD (2 lesions; 15%) and 10 with nonsclerotic cGVHD (11 lesions; 85%) necessitating skin biopsy. RCM can detect features commonly reported in cutaneous GVHD and is comparable to HP. Additional characterization of cutaneous GVHD by RCM may enable future use in diagnosing, monitoring, or predicting disease in real time.

Primary cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome. Part II: Prognosis and management.

Primary cutaneous T-cell lymphomas (CTCLs) other than mycosis fungoides (MF) and Sézary syndrome (SS) encompass a heterogenous group of non-Hodgkin lymphomas with variable clinical courses, prognoses, and management approaches. Given the morphologic and histologic overlap among the CTCL subtypes and other T-cell lymphomas with cutaneous manifestations, thorough evaluation with clinicopathologic correlation and exclusion of systemic involvement are essential prior to initiating therapy. Staging and treatment recommendations vary, depending on the subtype, clinical behavior, and treatment response. Generally, for subtypes in which staging is recommended, Ann Arbor or tumor, node, metastasis staging specific to CTCL other than MF or SS are used. For many subtypes, there is no standard treatment to date. Available recommended treatments range widely, from no active or minimal intervention with skin-directed therapy to aggressive systemic therapies that include multi-agent chemotherapy with consideration for hematopoietic stem cell transplant. Emerging targeted therapies, such as brentuximab, a chimeric antibody targeting CD30, show promise in altering the disease course of non-MF/SS CTCLs.

Primary cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome. Part I: Clinical and histologic features and diagnosis.

Primary cutaneous T-cell lymphomas (CTCLs) are defined as lymphomas with a T-cell phenotype that present in the skin without evidence of systemic or extracutaneous disease at initial presentation. CTCLs other than mycosis fungoides and Sézary syndrome (SS) account for approximately one third of CTCLs and encompass a heterogenous group of non-Hodgkin lymphomas, ranging from indolent lymphoproliferative disorders to aggressive malignancies with a poor prognosis. The spectrum of CTCLs continues to broaden as new provisional entities are classified. Given the morphologic and histologic overlap among CTCLs and other diagnoses, a thorough clinical history, physical evaluation, and clinicopathologic correlation are essential in the work up and diagnosis of these rare entities. This article will summarize the epidemiologic, clinical, pathologic, and diagnostic features of CTCLs other than mycosis fungoides and SS.

Association of interleukin-6 and tumor necrosis factor-α with mortality in hospitalized patients with cancer.

BACKGROUND: Severe cutaneous adverse reactions (SCARs) are associated with high morbidity and mortality in patients with cancer. Early identification and treatment of SCARs may improve outcomes. OBJECTIVE: To identify biomarkers to predict outcomes in hospitalized patients with cancer who developed SCARs. METHODS: Retrospective review of 144 hospitalized patients with cancer with a morbilliform rash, recorded testing for serum cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor [TNF]-α) or elafin, and a dermatology consultation. Rashes were categorized as simple morbilliform rash without systemic involvement or complex morbilliform rash with systemic involvement. RESULTS: Fifty-four of 144 (37.5%) patients died during follow-up. Elevated levels of IL-6, IL-10, and TNF-α were associated with decreased survival. Overall survivals in patients with elevated levels of IL-6, IL-10, and TNF-α were 53.7%, 56.6%, 53.6%, respectively, compared with 85.7%, 82.5% and 83.6%, respectively, in those with lower levels. Patients with increased levels of both IL-6 and TNF-α had a nearly 6-fold increase in mortality (hazard ratio, 5.82) compared with patients with lower levels. LIMITATIONS: Retrospective design, limited sample size, and high-risk population. CONCLUSIONS: Hospitalized patients with cancer with rash and elevated IL-6 and TNF-α were nearly 6 times more likely to die over the course of follow-up. These biomarkers may serve as prognostic biomarkers and therapeutic targets for this high-risk population.