RESUMEN
Background: Despite the profound effect that checkpoint inhibitors and BRAF/MEK inhibitors have had on survival in patients with metastatic melanoma, treatment options remain limited for those who demonstrate poor response or develop resistance to these modalities. The prospect of tumor sensitization to these treatments is therefore an attractive one. Results: We describe the case of a patient who developed a sustained response to trametinib and pembrolizumab, despite prior resistance to both these therapies, after receiving treatment with a CDK4/6 inhibitor. Discussion: We further outline the preclinical data supporting a possible role for the use of CDK4/6 inhibitors in tumor sensitization to immunotherapy.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Imidazoles/uso terapéutico , Inmunoterapia/métodos , Melanoma/tratamiento farmacológico , Oximas/uso terapéutico , Piridonas/uso terapéutico , Pirimidinonas/uso terapéutico , Anticuerpos Monoclonales Humanizados/inmunología , Antineoplásicos/inmunología , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 4 Dependiente de la Ciclina/inmunología , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/inmunología , Humanos , Imidazoles/inmunología , Masculino , Melanoma/inmunología , Persona de Mediana Edad , Oximas/inmunología , Piridonas/inmunología , Pirimidinonas/inmunología , Resultado del TratamientoRESUMEN
Ochroconis spp. are dematiaceous fungi and have recently become recognized as the cause of human disease. Infections due to members of this genus have primarily occurred in patients with impaired immunity following organ transplantation or chemotherapy for hematologic malignancies. There is no universally agreed upon therapy or duration of treatment, but amphotericin B and/or triazoles are typically employed. We present a case of Ochroconis gallopava infection in a patient with chronic granulomatous disease (CGD). The organism exhibited elevated minimal inhibitory concentrations against itraconazole (0.5 µg/ml) and voriconazole (2 µg/ml) in comparison with results from other studies reported in the literature. This case illustrates the complexities associated with antibiotic susceptibility testing, selection of appropriate drugs, and management in patients with Ochroconis infections. We also review the literature of human infections with Ochroconis to date, and discuss its microbiology to apprise both clinicians and laboratory personnel of this infrequently encountered but potentially aggressive pathogen.