Prognostic value of the “dynamic” second revision of the international staging system (R2- ISS) in patients with multiple myeloma undergoing anti-CD38 antibody, carfilzomib, and dexamethasone therapy

Abstract Recently, the second revision of the International Staging System (R2-ISS) has emerged as a prognostic tool for multiple myeloma (MM) and is known to be useful for prognostication at the time of diagnosis. Treatment outcomes for MM have significantly improved with the introduction of novel agents; however, eventual relapses nevertheless occur frequently, leading to refractory disease. Clonal evolution during relapse often results in high-risk cytogenetic abnormalities (HRCAs). Hence, a patient’s disease risk may change during their treatment course. We retrospectively analyzed whether R2-ISS influenced prognosis at treatment initiation in patients receiving anti-CD38 antibody, carfilzomib, and dexamethasone (Kd) treatments. HRCAs were examined from diagnosis to treatment initiation and considered positive if detected once. R2-ISS was recalculated at treatment initiation and defined as dynamic R2-ISS. Data from 60 patients who underwent the defined treatments were analyzed. The median observation period was 13.0 months, with a median progression-free survival (PFS) of 20.7 months. Median overall survival (OS) was not reached. Dynamic R2-ISS significantly stratified prognoses for both PFS and OS (P = 0.00011 and 0.023, respectively). The median PFS for patients with dynamic R2-ISS IV was 4.4 months, and the median OS was 14.6 months, indicating extremely poor outcomes. Multivariate analysis considering disease progression at treatment initiation, triple-class refractory status, and dynamic R2-ISS showed that only R2-ISS significantly affected both PFS and OS (P = 0.0041 and 0.019, respectively). Dynamic R2-ISS therefore shows potential as a prognostic tool in patients with MM who are treated via anti-CD38 antibody + Kd therapy.