Purpose: Rituximab has been successfully used in the treatment of B-cell non-Hodgkin's lymphoma (NHL) and some autoimmune diseases nearly for a decade. Several other malignancies and CD20-negative lymphomas have been reported in the literature after rituximab treatment. We aimed to investigate whether there is an association between rituximab treatment and the development of second malignancies.
Methods: A detailed search in English language literature on reports about rituximab treatment and secondary malignancies was made through Medline. The papers were reviewed and the cases were summarized according to secondary tumor types, intervals between rituximab treatment and second malignancy occurrence, indications for rituximab treatment and cytotoxic chemotherapy administration.
Results: There were 26 previously reported cases of CD20-negative lymphoma and solid tumors after rituximab treatment. The median age of these cases was 62 years (range 34-80). The median time period from the initiation of rituximab treatment to diagnosis of second malignancies was 5 months (range 1-40). The most frequently reported solid tumors were skin tumors (squamous cell carcinoma and Merkel cell carcinoma) (n=7; 27%), CD20-negative lymphomas (n=5; 20%), Kaposi sarcoma (n=4; 15%), and others (n=10; 38%).
Conclusion: Association between rituximab and subsequent development of second malignancies might be a coincidence. However, we suggest close monitoring for second malignancies, particularly skin tumors, in patients treated with rituximab. This issue should be evaluated in further studies.