Long-lasting Responses to Immunomodulatory Drugs (IMIDs) in Combination with Dexamethasone in Multiple Myeloma; Identification of Exceptional Responders at any Treatment Line

Background: There is a growing interest in the study of patients that achieve exceptionally long-lasting remissions although suffering from incurable neoplastic disorders. This is the case for multiple myeloma (MM), the treatment of which has greatly improved with the emergence of new, biology-driven modalities that prolonged survival. The identification of “exceptional responders” to basic treatment such as immunoregulatory drugs (IMIDs) and dexamethasone could eventually reveal a small proportion of patients potentially curable with more drugs combinations. Aims: To investigate MM exceptional responders to IMiDs. Objectives: To identify exceptional responders among all patients with symptomatic MM treated either at diagnosis or in relapse with an IMID (thalidomide, lenalidomide, pomalidomide) in combination with dexamethasone and to study their clinical characteristics and survival. Materials and Methods: A cohort of 164 patients was studied. “Exceptional responders” were defined as patients that remained in remission for at least 72 months after 1st line treatment, 60 months after 2nd line, 42 months after 3rd to 6th line and for at least 30 months beyond 6th line. Statistical analysis was performed using the SPSS v.24.0 software. Survival was evaluated by the log rank test. Results: Thirty-one (19%) exceptional responders were detected, of whom 11 (15%) out of 75 received thalidomide/dexamethasone (TD), 18 (14%) out of 132 lenalidomide/dexamethasone (LD) and 2 (25%) out of 8 pomalidomide dexamethasone (PD). The median number of treatment lines received prior to TD, LD and PD treatment was 2, 2 and 7 respectively. Exceptional responders' survival from TD, LD and PD treatment to last followup or death was 85, 73 and 35 months while their overall survival was 95, 94,5 and 149 months respectively. Seventeen patients are alive and 4 disease-free. They did not exhibit specific clinical or biochemical profile beside the absence of hypercalcemia and extramedullary disease at treatment initiation. Conclusion: We identified exceptional responders to IMIDs-based treatment, their further examination may enlighten on disease biologic aspects that could open the way to cure.