Adjunct Terbinafine in Patients With Leukemia and Invasive Fusariosis With Skin Lesions: Discordance Between Responses of Skin Lesions and Systemic Outcomes

To theEditor—Invasive fusariosis (IF) is a severe opportunistic mold infection that often results in poor outcomes, especially for patients with hematological malignancies [1–4]. Skin involvement is the second most common manifestation of IF after pulmonary involvement [1–3]. While in vitro studies showed synergistic effects of the squalene epoxidase inhibitor terbinafine (TRB) when combined with triazoles [5] or liposomal amphotericin B (L-Amb) [6] against various fungal pathogens, including Fusarium species, clinical data to support these findings are limited. As TRB has poor penetration in lungs and other visceral tissues, in contrast to its excellent concentration in skin [7], we hypothesized that there might be discordance between good responses of Fusarium skin lesions to TRB but poor systemic outcomes in IF patients treated with adjunct TRB (aTRB). Therefore, we retrospectively reviewed adult leukemia patients (aged ≥18 years) with culture-documented IF at MD Anderson Cancer Center (Houston, Texas) from 2009 to 2021. Among 140 IF patients (114 proven, 26 probable, European Organization for Research and Treatment of Cancer Mycoses Study Group definitions) [8], 71 patients (51%) had skin involvement. Of those, we identified 14 patients who received oral aTRB (dose range, 250–1000 mg/day; duration, 3–128 days) (Table 1). Their median age was 46 years (range, 21–80 years); 13 (93%) were male. Ten patients (71%) had acute myeloid leukemia/myelodysplastic syndrome. All patients had neutropenia (<500/µL) and 4 (29%) had undergone prior allogenic hematopoietic stem cell transplantation. The majority (13 patients [93%]) had disseminated skin lesions. In addition to aTRB, 13 patients received voriconazole + L-Amb and 1 received posaconazole + L-Amb. The median time from IF diagnosis to aTRB initiation was 8 days (range, 0–74 days). While skin lesions on day 42 after aTRB initiation or at the time of earlier death were improved (5 patients [36%]) or stabilized (4 patients [29%]) in 64% of patients, 10 of 14 (71%) had progression of IF in sites with poor pharmacologic exposures of aTRB (lungs in 7 patients, sinus in 2 patients, endophthalmitis in 1 patient). Notably, 71% of patients died within 42 days of aTRB initiation.