Improved survival in Myeloma patients undergoing ASCT is entirely in the standard cytogenetic risk groups.

Introduction Novel drugs and drug combinations have improved outcomes for multiple myeloma patients. However, subgroups of patients still have a poor progression-free survival (PFS) and overall survival (OS). In an attempt to identify how the novel drugs affect the outcome in standard-risk and high-risk patients, respectively, we have investigated 715 multiple myeloma (MM) patients who have undergone high dose treatment followed by autologous stem cell transplantation at our center during 1995 - 2020. Outcomes during three time periods, 1995-1999 (period I), 2000-2009 (period II), and 2010-2020 (period III), were compared separately for standard-risk and high-risk patients. Risk stratification was based on chromosome analysis for periods II and III. Results The whole cohort of patients showed significantly improved OS with time during the three periods being at a median of 5.8, 7.0, and 10.0 years, respectively. There is also a weak tendency for improved PFS, that is, a median of 2.4, 2.6, and 2.9 years, respectively, during the same periods. However, the separate analysis of standard-risk and high-risk patients showed that the overall improvement with time was due to improved standard-risk patients (median OS 8.4 years for the period I and not reached for period II and III). In contrast, no significant improvement was seen in high-risk patients. For patients with del17p, PFS was even worse during period III as compared to period II (median 1.6 vs 3.2 years respectively). Conclusion Our results show that the dramatic improvement in outcome for MM patients during the last 20 years only applies for standard-risk patients, while high-risk MM patients still are doing poorly, indicating that the novel drugs developed during this time are preferentially effective in standard-risk patients. New treatment modalities like CAR-T cells, CAR-NK cells, and/or bispecific antibodies should be tried in clinical studies early in the course of the disease, especially in patients with high-risk cytogenetics.