Complete Response to tenalisib and romidepsin with long-term maintenance using tenalisib monotherapy in a patient with relapsed and refractory sézary syndrome.

Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common subtypes of cutaneous T cell lymphomas (CTCL). Advanced-stage MF/SS have poor prognoses and may be refractory to multiple systemic treatments. These cases can be difficult to achieve and maintain complete response and there is a need for novel therapeutics. Inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway by Tenalisib presents one such emerging drug. We report a relapsed/refractory SS patient achieving complete remission using the combination of Tenalisib and Romidepsin and subsequently maintaining long-duration CR with Tenalisib monotherapy.

Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti-CTLA4 and anti-PD1 combination immunotherapy: Incidence, management, and clinical benefit.

BACKGROUND: In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. METHODS: Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. RESULTS: Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0-341 days) and 50 days (range, 1-352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P = .039). CONCLUSIONS: CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit.

Biologic therapies for checkpoint inhibitor-induced cutaneous toxicities: a single-institution study of 17 consecutively treated patients.

PURPOSE: Treatment options for corticosteroid-refractory and/or high-grade checkpoint inhibitor (CPI)-induced cutaneous adverse events (CAEs) are limited; however, anecdotal reports of biologic therapies have been successful. We aim to characterize the appropriate treatment scenarios and safety and efficacy profiles of biologics used to treat patients with CPI-induced CAEs at a single institution. METHODS: This is a retrospective case series of patients from January 1st, 2015 to October 20th, 2020, with CPI-induced CAEs who were treated with biologics at a single cancer center. Patients were identified using institutional electronic medical record who underwent CPI therapy with subsequent CAEs that necessitated biologic therapy. Diagnostic criteria utilized for CAEs were based on documentation by four board-certified dermatologists, in combination with detailed chart reviews and pathology findings. Primary study outcome measurements include CAE response, tumor response, and adverse events during biologics treatment. RESULTS: We identified 17 patients who fit study criteria. Sixteen patients experienced some degree of CAE improvement on biologics, with 10 of 10 patients reaching CAE resolution at 6 months post biologics. Eight patients needed new systemic treatment post biologics treatment, while 9 patients received no further treatment or stayed on the CPI. Thirteen patients tolerated biologics well with no significant adverse events or blood abnormalities, with only 2 patients experiencing biologic dose delays. CONCLUSION: In our cohort, biologics appear to be extremely efficacious in the treatment of severe-grade and/or steroid refractory CAEs. They also appeared to be well-tolerated without overtly negative effects on tumor response. In patients with limited cancer treatment options and good tumor response to CPIs, biologics should be considered for severe-grade and/or refractory CAEs.

Unusual presentation of Kaposi sarcoma in an HIV-negative woman.

Kaposi sarcoma typically presents as violaceous macules and papules in immunocompromised, specifically HIV-positive, patients. Its distinct clinical features often facilitate rapid diagnosis. In this article, we report a case of Kaposi sarcoma presenting as a concerning yet nondescript lesion in an HIV-negative woman. Although Kaposi sarcoma is frequently part of the differential diagnosis for skin lesions affecting HIV-positive patients, it is less frequently considered in HIV-negative individuals. Additionally, this case differs from the classic clinical presentation of Kaposi sarcoma by resembling a squamous cell carcinoma or superficial basal cell carcinoma. Therefore, it illustrates the importance of suspicious lesion biopsies to ensure accurate diagnosis and appropriate treatment.

Achromobacter xylosoxidans Bacteremia and Cellulitis: A Report of a Case.

Achromobacter xylosoxidans is a rare, opportunistic infection most commonly encountered in immunocompromised patients during hospitalization. Primary uncomplicated bacteremia, catheter-associated infections, and pneumonia have been reported as the most common clinical presentations; skin and soft tissue infections from A. xylosoxidans are rare. We describe a case of A. xylosoxidans presenting as cellulitis and bacteremia in an immunocompromised patient.

Toll receptor agonist therapy of skin cancer and cutaneous T-cell lymphoma.

PURPOSE OF REVIEW: The use of agents which exhibit the ability to potently activate the innate immune response has gained significant interest as therapeutics to treat cancer. We will review the history and the current applications of these agents to treat skin cancer and cutaneous T-cell lymphoma. RECENT FINDINGS: Particular attention has been focused upon Toll-like receptor (TLR) agonists, including imidazoquinolines, which can trigger TLR 7 and TLR 8, and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides, which activate TLR 9-expressing cells. Imiquimod, a TLR 7 agonist, has been found to be efficacious for basal cell and squamous cell cancers, as well as cutaneous T-cell lymphoma and lentigo maligna melanoma. CpGs have demonstrated efficacy for cutaneous T-cell lymphoma. Additional more potent compounds, including resiquimod, are presently in clinical trials for several types of skin cancers. SUMMARY: TLR agonists that can activate the innate immune response have been used to treat a variety of skin cancers including basal cell cancer, squamous cell cancer, lentigo maligna melanoma and cutaneous T-cell lymphoma. Significant clinical efficacy has been observed for all of these conditions. It is anticipated that additional members of the TLR agonist family will be available in the clinic for the future treatment of skin cancers as well as other malignancies.

Radiotherapy in the treatment of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.

BACKGROUND: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy. OBJECTIVE: Our aim was to characterize treatment options for PCSM-LPD, with a focus on the role of radiotherapy. METHODS: This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM-LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy. RESULTS: All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra-low-dose radiotherapy (4 Gy in 1-2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids. CONCLUSION: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra-low-dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy.

Hydrochlorothiazide and cutaneous T cell lymphoma: prospective analysis and case series.

BACKGROUND: Mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are the most common cutaneous T cell lymphomas (CTCL), but their etiology remains unknown. After patients were observed with hydrochlorothiazide (HCTZ)-associated CTCL, HCTZ was examined as a putative chronic antigen in a cohort of prospectively staged patients. METHODS: Demographic and drug exposure data was examined from 1443 confirmed MF and SS patients. Hypertensive CTCL patients were divided into HCTZ users or nonusers for statistical analysis by chi-square and t tests. Causality in a case series was rated by the Naranjo Adverse Drug Reaction Probability Scale. RESULTS: A total of 815 of 1443 MF and SS patients (56.5%) were hypertensive; 205 (25.2%) were taking HCTZ at initial staging. Comparing stage of patients who were using or not using HCTZ, the most significant difference was between stage I and stage IV (odds ratio of 0.45; 95% confidence interval of 0.25-0.78, P = .003), demonstrating reduced likelihood of being stage IV in patients who were on HCTZ. Seventy-seven percent of the MF patients on HCTZ were stage I. A total of 125 patients of 196 (63.8%) started HCTZ prior to developing CTCL lesions, and 35 of 121 (28.0%) started within 1 year of first skin rash. Thirty-six of 125 patients (28.8%) experienced complete or partial remissions after discontinuing HCTZ. A monoclonal T cell receptor rearrangement was detected more frequently in the hypertensive stage I patients not taking HCTZ as compared with those who were (55.3% vs 69.1%, P = .032). Three patients were rechallenged and developed MF lesions that resolved or improved with discontinuation. CONCLUSIONS: HCTZ is commonly prescribed and may be a putative antigen in a small subset of early MF patients. Careful drug histories and a trial off medication are warranted.

Safety of Concurrent Radiation Therapy With Brentuximab Vedotin in the Treatment of Lymphoma.

Purpose: Purpose: Radiation therapy (RT) and the antibody-drug conjugate brentuximab vedotin (BV) are standard-of-care treatment options for patients with certain B and T-cell lymphomas; however, there are limited data exploring the safety of concurrent BV and RT (BVRT). Methods and Materials: We performed a single institutional retrospective review of 44 patients who received BVRT. Results: Twenty percent of patients (9/44) developed new grade 2 or higher (G2+) hematologic toxicity (HT) after BVRT, which was associated with radiation dose (median dose of 35 Gy in those with new G2+ HT compared with 15 Gy in those without; P < .001). Acute G2+ elevation in aspartate transaminase or alanine transaminase level was associated with administration of concurrent chemotherapy with BVRT (57% vs 21%; P = .047) but was not associated with any RT factors. Local control (LC) was achieved in 24 of 42 patients (57%) with available follow-up. Ten patients (23%) proceeded to stem cell transplant or cellular therapy after BVRT at a median of 48 days (interquartile range, 27-188 days). At last follow-up, 10 patients (23%) remained without evidence of disease. Conclusions: Our analysis demonstrates that the combination of BV and RT is well tolerated, though care should be taken during RT planning to reduce the risk of HT. This combination can be considered for patients in need of both local and systemic disease control.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in erythrodermic cutaneous T-cell lymphoma (CTCL) patients.

Erythroderma can occur in cutaneous T-cell lymphoma (CTCL). Staphylococcus aureus (S. aureus) prevalence is increased in CTCL patients and contributes to CTCL disease flares. Our primary aim was to describe S. aureus infections, including resistance patterns and the antibiotic treatment regimens used, in erythrodermic CTCL patients. This was a retrospective chart review of erythrodermic CTCL patients who had S. aureus infection or colonization and were treated at the UT MD Anderson Cancer Center's Melanoma Skin Center between 2012 and 2016. Twenty-six erythrodermic CTCL patients had 50 documented S. aureus colonization or infection events. Patients had an improvement in body surface area (BSA) or modified Severity Weighted Assessment Tool (mSWAT) in 53% events treated for S. aureus. Seventeen of the 50 (34%) events were due to methicillin-resistant S. aureus (MRSA). One-third (33%) of MRSA events were initially treated with dicloxacillin. The MRSA isolates were sensitive to trimethoprim-sulfamethoxazole (92%) and doxycycline (88%). Patients treated in the outpatient setting (OR 0.073; 95% CI 0.008-0.627; p = 0.017) and patients with a previous history of topical anti-S. aureus decolonization treatments before S. aureus event as stand-alone (OR 0.125; 95% CI 0.018-0.887; p = 0.038) or in combination treatment with systemic antibiotics (OR 0.094; 95% CI 0.009-0.944; p = 0.045) were less likely to see improvement in BSA or mSWAT from S. aureus treatment. Treatment of S. aureus improved CTCL skin score in a high number of erythrodermic patients. The MRSA prevalence was high in erythrodermic CTCL patients. Clinicians should consider using empiric MRSA antibiotic coverage for these patients.

A case report of bosutinib-induced interstitial granulomatous drug reaction in a patient with chronic myelogenous leukemia: a case report.

Bosutinib is a BCR-ABL tyrosine kinase inhibitor approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia. We report a case of bosutinib-induced interstitial granulomatous drug reaction in a 50-year-old Caucasian female with chronic myelogenous leukemia. Histologic analysis of a punch biopsy showed diffuse interstitial granulomatous infiltrates consisting of histiocytes amid thickened collagen accompanied by eosinophils. Her lesions improved with clobetasol 0.05% cream. No cases describing BCR-ABL tyrosine kinase inhibitor-associated interstitial granulomatous drug reaction were found in a search of the literature. It is important for physicians to be aware of the risk of interstitial granulomatous drug reaction associated with bosutinib treatment.

Brentuximab Vedotin for Patients With Refractory Lymphomatoid Papulosis: An Analysis of Phase 2 Results.

Importance: Brentuximab vedotin is a monomethyl auristatin E-conjugated monoclonal antibody directed against CD30. It represents a potential treatment for the CD30+ lymphoproliferative disorder lymphomatoid papulosis (LyP), which currently has no approved treatment. Objective: To assess the efficacy and safety of brentuximab vedotin for the treatment of LyP. Design, Setting, and Participants: In this study conducted at The University of Texas MD Anderson Cancer Center from May 10, 2011, to March 31, 2017, a total of 12 patients with LyP received brentuximab vedotin. All patients were 18 years or older with a diagnosis of LyP and were also required to have scarring, more than 10 lesions, or active lesions on the face, hands, or feet. Nine patients were enrolled in a physician-initiated, open-label, single-center, phase 2 clinical trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphomas and LyP from 2011 to 2013. Three patients were later treated outside of the trial from 2013 to 2017. Five patients continued to be followed up as of March 2017. Interventions: Intravenous brentuximab vedotin 1.8 mg/kg infused over 30 minutes every 21 days. Main Outcomes and Measures: The primary end point was the overall response rate. Complete response was defined as zero lesions, and partial response was defined as a 50% or greater reduction in lesion count from baseline. A relapse was defined as loss of partial response. Results: All 12 patients (8 men and 4 women; median age, 46 years) responded to brentuximab vedotin, and 7 exhibited a complete response. Time to response was 3 weeks in all patients. The median duration of response was 20 weeks (range, 6-103 weeks). For 5 patients who relapsed, the median time to relapse was 12 weeks (range, 6-41 weeks). One patient who relapsed was retreated and has remained in partial response for more than 23 months. Grade 1 to 2 neuropathy occurred in 10 patients but resolved in 5. Adverse events of grade 3 or higher were neutropenia (n = 2) and dizziness/vertigo (n = 1). Three patients withdrew owing to adverse events. Conclusions and Relevance: Brentuximab vedotin is effective in treating LyP (overall response rate, 100%; complete response rate, 58%), but its use should be reserved for patients with truly severe and refractory LyP. More work is needed to optimize its dosing to minimize adverse events, such as peripheral neuropathy. Trial Registration: clinicaltrials.gov Identifier: NCT01352520.

The Role of Systemic Retinoids in the Treatment of Cutaneous T-Cell Lymphoma.

Retinoids are natural and synthetic vitamin A analogs with effects on cell proliferation, differentiation, and apoptosis. They have significant activity in hematologic malignancies and have been studied extensively in cutaneous T-cell lymphoma. Retinoids bind to nuclear receptors and exert their effects through moderation of gene expression. Retinoic acid receptor and retinoic X receptor exert regulatory activity in vivo, binding to distinct ligands. Studies investigating systemic retinoids as monotherapy and in combination with other agents active against cutaneous lymphoma are reviewed. Side effects associated with retinoids include teratogenicity, dyslipidemias, and hypothyroidism, which should be carefully monitored in patients receiving treatment.