Characterizing cutaneous toxicity from doxorubicin.

Abstract

e19084 Background: While pegylated liposomal doxorubicin (PLD) is associated with reduced cardiac toxicity and improved efficacy in cutaneous malignancies when compared to conventional doxorubicin, its use is often limited by cutaneous toxicity and infusion-related reactions (IRR). It is not clear whether these toxicities differ by race, dosing strategy, or site of neoplastic involvement. Methods: All patients with mycosis fungoides / Sezary syndrome (MF / SS), Kaposi sarcoma (KS), or leiomyosarcoma (LMS) who received treatment with PLD between January 2008 and December 2023 at Johns Hopkins Hospital were analyzed. Standard population statistics were used. Patients who received only 1 dose of PLD for any reason were not included in the remaining evaluations. Results: A total of 125 patients were identified, including 36 with MF / SS, 33 with KS, and 56 with LMS. Among these, race was black in 68 (24 in MF / SS, 25 in KS, and 19 in LMS). The median age was 56 years (range, 24-86). Dosing of PLD with each infusion was 20 mg/m2 in 68, 40 mg/m2 in 23, 45 mg/m2 in 13, and 50 mg/m2 in 16. PLD was administered for a median of 4 cycles (range, 1-50) and 12 weeks (range, 1-120). A total of 15 patients experienced an IRR. Cutaneous toxicity occurred in 25 patients (20%) at a median of 75 days (range, 7-280). Cardiac toxicity occurred in 3. Treatment with PLD was discontinued for toxicity in 17 patients (11%). Univariate analysis revealed no significant associations between cutaneous toxicity and age, race, cutaneous involvement of malignancy, or PLD frequency, dosing, or total duration. There were no predictors of cutaneous toxicity by tumor stage, SS, or large cell transformation (LCT). The overall response rate (ORR) was 37% among the entire cohort and 65% among those with cutaneous malignancies (p<0.001), reflecting low responses in the LMS cohort (5%) relative to MF / SS (59%) and KS (71%). Black race was associated with improved ORR (p <0.001), though this association did not hold when limiting assessment to those with cutaneous malignancies, where black race was more frequent. Conclusions: This retrospective study of 125 patients represents the largest study to date dedicated to the characterization of PLD toxicity. Among patients with MF / SS, KS, and LMS, treatment with PLD was associated with cutaneous toxicity in 20% of patients, which did not appear to vary by race, cutaneous involvement of malignancy, or dosing strategy. Future investigation will include a more detailed assessment of the MF/SS population, clinicopathologic correlation for those with cutaneous toxicity, and an attempt to identify potential risk factors for those who experienced cardiac toxicity or IRR. Pegylated liposomal doxorubicin cutaneous toxicity and response. Cutaneous toxicity ORR Whole cohort Black race Cutaneous malignancy Whole cohort Black race Cutaneous malignancy All 20% (25/125) N/A 18% (12/68) p=0.51 20% (12/69) p=0.50 37% (44/119) N/A 52% (32/62) p<0.001 65% (41/63) p<0.001