Real-world assessment of treatment patterns and outcomes in patients with relapsed-refractory multiple myeloma in an Italian haematological tertiary care centre.

Despite significant improvements in therapeutic options, multiple myeloma (MM) patients experience a series of remissions and relapses requiring further lines of therapy (LOTs). We analysed treatment pathways, attrition rates (ARs) and refractoriness patterns across LOTs in 413 MM patients treated from 2011 and 2021. Across LOT-2 to LOT-5 ARs were 26%, 27%, 34% and 37.5%, being 50% for subsequent LOTs. In univariate analysis age over 65 years, international staging system (ISS) II/III, more than two comorbidities, no transplant and no maintenance therapy were significantly associated with AR but regression analysis selected only age over 65 years and more than 2 comorbidities. Median progression-free survival (PFS) was 40.5, 19.5, 10.3, 6 and 4.7 months from LOT-1 to LOT-5. Lenalidomide-refractory patients, among those relapsed after LOT-1, were 26% and 64.5% respectively, in patients starting therapy before 2019 versus in or after 2021. In the two cohorts, 57.5% and 85.5% of patients relapsed after LOT-2 were lenalidomide-refractory. Among patients not relapsed from LOT-1, 80% are receiving continuous lenalidomide and could become lenalidomide-refractory, whereas 91% and 51.5% of patients in LOT-2 could become potential lenalidomide- and daratumumab-refractory respectively. In our analysis the rate of patients reaching subsequent LOTs was higher than previously reported and the increase in early refractoriness would require faster and more efficient treatment licensing processes.

An update on novel multiple myeloma targets.

INTRODUCTION: Despite therapeutic progress, leading to a significant improvement of outcome, multiple myeloma (MM) remains a difficult to treat hematologic disease due to its biological heterogeneity and clinical complexity. AREAS COVERED: Treatment of patients refractory and resistant to all classes of agents used in newly diagnosed MM is becoming a relevant problem for every hematologist. New generation immunotherapies, such as conjugated mAb, bispecific mAbs and CAR-T cells, targeting novel molecules as BCMA, have showed relevant results in very advanced MM. In the same setting, small molecules, such as selinexor and melflufen, also proved to be effective. We are currently waiting for the results of under evaluation personalized therapy, directed against specific gene mutations or signaling pathways, responsible for disease progression. EXPERT OPINION: In the near future, many therapeutic strategies will become available for MM and the challenge will be to position each approach in order to cure, maintaining a good quality of life in these patients.