INTRODUCTION: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe hypersensitivity reaction rarely documented in patients with multiple myeloma (MM).

METHODS: In our retrospective study of 108 newly diagnosed MM (NDMM) patients from January 2021 to October 2023, we identified four cases of DRESS. The clinical characteristics such as clinical manifestations, laboratory results, treatment and outcome were analyzed.

RESULTS: These patients presented with fever, persistent and recurrent, along with a widespread red rash characterized by diffuse erythematous macules or papules accompanied by intense itching, desquamation, and other dermatological manifestations. Multi-organ involvement was common, including hepatic impairment, acute kidney injury, and type I respiratory failure, alongside pleural effusion and multiple lymphadenopathy. Laboratory findings revealed elevated eosinophil counts, often exceeding 1.5 × 10^9/L, abnormal liver function tests, acute kidney injury, and inflammatory markers. Anti-MM treatment was promptly suspended, and all patients received corticosteroid therapy. Outcomes varied, with one patient succumbing to myeloma progression, another to multi-organ failure, while the remaining two patients survived.

CONCLUSION: In NDMM patients undergoing induction therapy, occurrences of DRESS are infrequent but noteworthy, with an incidence higher than observed in the general population. It presents with significant morbidity and mortality, highlighting the crucial need for early recognition and management.