This month’s news from across the specialty
What’s hot
August 1, 2024
In this monthly column, members of the DermWorld Editorial Advisory Workgroup identify exciting news from across the specialty.
Several physician groups have recently modified the staging and classification of all primary cutaneous lymphomas (PCL). Changes to the evaluation and classification of mycosis fungoides/sezary syndrome (MF/SS) and the other PCLs include new information on the preferred type of imaging, biopsy of abnormal lymph nodes, and assessment of blood involvement in MF/SS. Patients with non-MF/non-SS PCLs are staged using a TNM classification, different from the TNMB classification used to stage patients with MF/SS. The T classification for skin in non-MF/non-SS PCLs uses the size and location of lesions relative to lymph node drainage areas of the skin, compared with the type of lesion and body surface area covered by lesions in MF/SS.
Modifications include the addition of human T-lymphotropic virus (HTLV) I/II in standard blood work and considering LNs greater than 1.5 cm in diameter on physical exam or imaging for staging or biopsy. Imaging such as CT or PET are recommended for greater than stage 1A/limited 1B or if habitus precludes accurate assessment in clinical trials. Sezary count and CD4:CD8 ratio are no longer recommended. The absolute number of aberrant lymphocytes should be determined by flow cytometry, using their list of current best markers for assessing blood tumor level. The modified skin (T) staging of PCLs should be saved for quick clinical reference when assessing CTCL patients. PCL should be in the differential diagnosis of persistent erythroderma, patches, plaques, or enlarging tumors. A low threshold for skin biopsy is recommended when assessing these patients.
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Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome is a rare autosomal-dominant immunodeficiency caused by CXCR4 gain-of-function variants. However, less than one in four patients has all four classic manifestations. Thus, dermatologists should consider this syndrome when evaluating patients with warts and signs or symptoms suggestive of immunodeficiency, like sinopulmonary infections, respiratory tract infections, ear infections, skin infections, recurrent or difficult to treat warts, neutropenia, lymphopenia, and hypogammaglobulinemia.
In April 2024, mavorixafor (Xolremdi), which is an oral CXCR4 antagonist, was approved by the FDA for the treatment of patients 12 and older with WHIM syndrome. This is the first drug specifically FDA-approved to treat these patients. The approval is based on a randomized, double-blind, placebo-controlled, phase 3 trial of 31 participants (doi.org/10.1182/blood.2023022658). Use of mavorixafor was associated with numerous benefits: higher neutrophil and lymphocyte counts, reduced annualized and total infection rates, and reduced infection frequency, severity, duration, and antibiotic use. Mavorixafor was also well-tolerated with no related serious adverse events.
If faced with a patient with possible WHIM syndrome, dermatologists might find the online resources available at www.whatifitswhim.com helpful (the website was created by X4 pharmaceuticals, the manufacturer of mavorixafor). Resources include a physician diagnosis guide, no-cost genetic testing with Invitae, patient educational tools, and nurse educators.
Frintner et al completed the first national comparison of U.S. physicians’ satisfaction and wellbeing before and during the COVID-19 pandemic. The study followed a national sample of pediatricians from 2012-2021. Career satisfaction did not decrease during the pandemic; however, female pediatricians (but not male pediatricians) reported increased rates of anxiety, sadness, and stress at work. Interestingly, females did not report increased stress balancing home and work responsibilities during the pandemic. However, females consistently reported twice the amount of stress in this area during the entire decade of the study. This is consistent with many previous studies showing that women physicians tend to have more household and childcare responsibilities than male physicians and shows that we cannot assume that everyone has the same stresses and responsibilities at home and work. The authors recommend that, especially in female-predominant specialties like dermatology and pediatrics, organizations and businesses should focus on programs and policies that ameliorate these disparities and better support female physicians.
More What’s Hot!
Check out more What’s Hot columns from the DermWorld Editorial Advisory Workgroup.
For many types of cancer, surgery with or without adjuvant therapy (e.g., radiation, immunotherapy, chemotherapy) remains the standard of care. However, there is a growing body of evidence that neoadjuvant immunotherapy may be vastly more efficacious than adjuvant therapies. Studies of neoadjuvant immunotherapy across various types of cancer support the hypothesis that an intact tumor microenvironment — undisturbed by surgery and with an abundant repertoire of tumor neoantigens — elicits the most vigorous and successful immune response to immunotherapeutics.
Several cohort and phase 2 studies on the neoadjuvant use of cemiplimab or pembrolizumab in high-risk, locally advanced cSCC have demonstrated the high efficacy of neoadjuvant immunotherapy (doi: 10.1056/NEJMoa2209813; doi:10.1001/jamaoto.2024.0259, and doi: 10.1016/S1470-2045(23)00459-X). A new phase 3 study in the NEJM supports the use of neoadjuvant ipilimumab plus nivolumab in the treatment of melanoma without concomitant chemotherapy (doi:10.1056/NEJMoa2402604). Patients with resectable, macroscopic stage III melanoma were randomized to receive either (i) neoadjuvant therapy with ipilimumab plus nivolumab followed by surgery, or (ii) surgery followed by adjuvant therapy with nivolumab (the current standard of care). The study reports an impressive 68% relative risk reduction for disease recurrence or death in the neoadjuvant compared to the adjuvant immunotherapy cohort. The estimated one-year, event-free survival rate was 83.7% in the neoadjuvant group compared to 57.2% in the adjuvant group.
With a strong biologic basis to explain robust antitumor effect in neoadjuvant immunotherapy and numerous studies demonstrating such beneficial results, we must consider the potential for neoadjuvant immunotherapy to become a new standard of care.
