SY30-3 - The difficulty in establishing clinical evidence of extremely-rare hematological malignancies

Abstract

Remarkable renovations in standard of care by novel drugs have been made in some hematological malignancies for the past two decades, but not significantly in adult T-cell leukemia/lymphoma (ATL) which is a lymphoid malignancy caused by human T-lymphotropic virus type-I. The main reasons for little progress are its rarity, heterogeneity and aggressiveness. The number of patients of newly-diagnosed ATL is estimated to be less than 1000/year in Japan, and those diagnosed outside Japan are mainly from developing countries. In these 6 years, two drugs, a CCR4 monoclonal antibody, mogamulizumab and an immunomodulatory drug, lenalidomide, have been approved for ATL in Japan as orphan drug. The number of patients involving in the clinical trials for approval was very low, and importantly their background characteristics appeared to be different from those in practice. The substantial number of patients could not be enrolled into the trials due to poor performance status and rapid progression of the disease. On the other hand, if more aggressive patients were enrolled, it is likely to fail to show the efficacy. Well-designed postmarketing study is thereby essential to validate its efficacy and toxicity in the real-world practice. Moreover, most recent clinical trials aiming to develop novel drugs for relapsed/refractory ATL are experiencing a tough time to complete. In addition to rarity of the disease, recommendation by the regulatory agency to target patients only after use of mogamulizumab precludes patients' registration. It is a standard strategy to evaluate new drugs after available drugs are used up as in other cancers, but it is not a case in ATL. Only a few patients who relapse on mogamulizumab or become refractory to it are eligible for clinical trials due to the aggressive nature of ATL. To develop novel treatment and to establish standard of care for ATL is still challenging, but it is a lesson to learn its strategy for rare and very aggressive diseases.