Ribociclib-Induced Cutaneous Adverse Events in Metastatic HR+/HER2- Breast Cancer: Incidence, Multidisciplinary Management, and Prognostic Implication.

BACKGROUND: Ribociclib is approved for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC) treatment, in combination with endocrine therapy. Hematological, hepatic, and cardiac adverse events (AEs) emerged from pivotal trials, but little is known about cutaneous adverse events (CAEs). PATIENTS AND METHODS: We report data from a retrospective cohort study of all patients with HR+/HER2- ABC treated with ribociclib at Humanitas Cancer Center between June 2017 and December 2022. We recorded clinical-pathological data, the incidence, and treatment of ribociclib-related CAEs. These were evaluated according to the NCI-CTCAE v5.0 classification. Progression-free survival (PFS) was estimated by Kaplan-Meier method and the log-rank test was used to analyze differences between groups. RESULTS: Thirteen of 91 patients (14.3%) experienced treatment-related CAEs (mean time to the occurrence: 3.9 months). The most frequent CAEs were eczematous dermatitis (53.8%) and maculo-papular reaction (15.4%). Itch was reported by all 13 patients. The grade was G3 in 8 cases, G2 in 4, and G1 in 1. An integrated approach based on ribociclib dose modulation and dermatological interventions (oral antihistamine, moisturized cream, topical, and/or systemic steroids) could prevent ribociclib discontinuation in most patients. At a median follow-up of 20 months, the median PFS was 13 months (range, 1-66) with a better PFS curves for patients experiencing CAEs (P = .04). CONCLUSION: We mapped frequency and types of ribociclib-induced CAEs. An interdisciplinary management of CAEs incorporated into routine care may reduce the rate of drug discontinuation thus potentially contributing to better long-term outcomes.

Mycosis fungoides in childhood: description and study of two siblings.

Primary cutaneous T-cell lymphomas are exceedingly rare in children and adolescents. However, mycosis fungoides (MF) is the most frequent primary cutaneous lymphoma diagnosed in childhood. Two cases of MF in siblings (a 14-year-old boy and his 10-year-old sister) are reported. On the basis of clinical features (histopathological and immunophenotypical findings) a diagnosis of MF patch lesions was made in both siblings. Since recent data in the literature have underlined a high frequency of the HLA-DQB1*03 allele in patients with familial MF (including child patients), the HLA profile of the patients was analysed, indicating the presence of a haplotype (HLA-DQB1*03,*03 in the girl, HLA-DQB1*02,*03 in the boy) corresponding with that described in recent literature. Two rare and exceptional cases of MF in siblings are reported, highlighting the presence of a peculiar haplotype.

Complete remission of brain metastases in three patients with stage IV melanoma treated with BOLD and G-CSF.

BACKGROUND: Brain metastases are the most life-threatening among the secondary localizations of melanoma for their unresponsiveness to the surgical, radiotherapeutic and/or chemotherapeutic treatments. METHODS: Accidentally, we observed a complete response (CR) in a patient undergoing chemotherapy with bleomycin, vincristine or Oncovin, CCNU or lomustine, dacarbazine (BOLD) regimen for metastatic melanoma including brain metastases, who was also treated with G-CSF to manage a concomitant leukopenia. After this observation, seven more patients with stage IV melanoma with brain metastases were treated with BOLD regimen repeated every 6 weeks with administration of G-CSF in the intervals. RESULTS: Three patients presented CR (37.5%). Two patients stopped the treatment after two courses for evident progressive disease (25%). The other three patients showed stable disease (SD: 37.5%). Median duration of SD was 24 weeks. Among the eight patients, six (75%) achieved clinical benefit. Median time to progression was 8.5 months (range 0-74+ months). Median survival was 12.5 months (range 4-74+ months). Two patients are still alive and disease-free after 74 and 57 months, respectively. CONCLUSION: We believe that the brilliant CR, the long duration of the disease-free intervals and the long survival in at least three of eight patients should encourage further research on BOLD with G-CSF for the treatment of advanced melanoma.

Radiation recall dermatitis, panniculitis, and myositis following cyclophosphamide therapy: histopathologic findings of a patient affected by multiple myeloma.

Radiation recall dermatitis is one of the skin sequelae that may affect oncology patients. It occurs in a previously irradiated field, when subsequent chemotherapy is given. The eruption may be elicited by chemotherapy, even several months after radiotherapy. Its mechanism is poorly understood, and the histopathologic findings have received, to date, only sketchy descriptions. A 55-year-old male affected by multiple myeloma received radiation therapy both on his left coxofemoral area, and lumbar region (D11-L1). After cyclophosphamide administration, he developed 2 well defined square-shaped, infiltrated erythematoviolaceous plaques in the prior irradiated fields. Histopathologic findings revealed a diffusely fibrosclerosing process, involving deep dermis, hypodermis, as well as the underlying muscle, while sparing the epidermis and superficial-mid dermis. Histopathology was indistinguishable from deep radio-dermatitis, panniculitis, and myositis. This is the first case providing clear evidence of the causative role of cyclophosphamide in inducing a cutaneous and subcutaneous radiation recall reaction.