Salvage treatment patterns in multiple myeloma patients progressing after lenalidomide maintenance: A real‐life study from European Myeloma Network (EMN) Italy

The extensive use of lenalidomide (Len) in the first-line treatment of multiple myeloma (MM) has resulted in an increased frequency of patients who have been exposed or are refractory to Len (Len-R) at first relapse. However, the outcome of Len-R patients treated at first relapse after autologous haematopoietic stem cell transplantation (AHSCT) remains unclear. The aim of this real-life study is to evaluate the effectiveness of the regimens licensed in Italy and used in a cohort of patients who relapsed during Len maintenance after AHSCT. We collected 306 patients with these features. Considering the different regimens used, most patients received isatuximab–carfilzomib–dexamethasone (Isa-KD) (45.4%) followed by daratumumab–pomalidomide–dexamethasone (D-PD) (19.3%) and daratumumab–bortezomib–dexamethasone (D-VD) (12.4%). Overall, a reduced progression-free survival (PFS) and overall survival (OS) were observed in patients with high-risk disease features at relapse, including high lactate dehydrogenase (LDH) (p = 0.0003 and p < 0.0001), International Staging System (ISS) ≥2 (p < 0.0001 and p < 0.0001) and early relapse (<12 months from maintenance initiation) (p = 0.0017 and p = 0.0009). Considering the type of treatment, anti-cluster of differentiation 38 (CD38) monoclonal antibodies (anti-CD38 MoAb)-based regimen displayed improved survival compared to the other treatment, with Isa-KD reporting the longest PFS (22.8 months). Our data in a homogenous cohort of Len-R patients treated at first relapse demonstrated that the anti-CD38 MoAb-based combinations, particularly Isa-KD, represented the standard of care before the approval of anti-B cell maturation antigen (BCMA) immunotherapy.