Characteristics and Outcomes of Patients With Relapsed/Refractory Multiple Myeloma After Exposure to Lenalidomide in First Line of Therapy: A Single Center Database Review in Greece

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 24; no. 7; pp. 468 - 477
• Main Authors: Kastritis, Efstathios, Ntanasis-Stathopoulos, Ioannis, Theodorakakou, Foteini, Migkou, Magdalini, Roussou, Maria, Malandrakis, Panagiotis, Kanellias, Nikolaos, Eleutherakis-Papaiakovou, Evangelos, Fotiou, Despina, Spiliopoulou, Vassiliki, Gavriatopoulou, Maria, Patel, Sachin, Majer, Istvan, Boukis, Christos, Fetani, Andriani, Dimopoulos, Meletios A., Terpos, Evangelos
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2024
• Subjects: Aged; Aged, 80 and over; Databases, Factual; Drug Resistance, Neoplasm; Female; Greece; Humans; Lenalidomide - therapeutic use; Lenalidomide-refractory; Male; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Real-world; Retrospective Studies; Second-line therapy; Survival; Treatment Outcome; Treatment strategy; Greece; Treatment strategy; Lenalidomide-refractory; Survival; Real-world; Second-line therapy
• ISSN: 2152-2650; 2152-2669; 2152-2669
• DOI: 10.1016/j.clml.2024.03.003

•Survival is poor in patients refractory to first-line lenalidomide (Len).•Limited real-world data on treatment patterns and outcomes exist in these patients.•Len-refractory patients commonly received proteasome-inhibitor and triplet regimens.•Survival times of optimal regimens were poor versus non-Len-refractory patients.•Len-refractory patients’ unmet need has driven the development of novel therapies. The increasing use of lenalidomide (Len) in first-line (1L) therapy of multiple myeloma (MM) has led to a significant proportion of patients becoming Len-refractory following 1L treatment. However, there are limited real-world data on treatment strategies and outcomes of patients who become Len-refractory following 1L therapy. This real-world retrospective cohort study analyzed Len-refractory and non-Len-refractory patients who received 1L Len and initiated second-line (2L) therapy at a Greek MM center. The Len-exposed cohort (n = 249) included 55.4% Len-refractory patients after 1L. Compared to non-Len-refractory patients, Len-refractory patients more frequently had high-risk cytogenetics and Revised-International Staging System-3 disease stage at diagnosis, and had shorter progression-free survival (PFS) following 1L therapy. Len-refractory versus non-Len-refractory patients more frequently received triplets (59% vs. 40%), anti-CD38 agents (20% vs. 9%) and pomalidomide (22% vs. 13%). The overall response rate was 53% for Len-refractory patients and 64% for non-Len-refractory patients in 2L therapy; median PFS was 10.7 vs. 18.3 months, respectively. Median overall survival (OS) was shorter for Len-refractory patients vs non-Len-refractory patients (23.8 vs. 53.6 months). Len refractoriness was an independent prognostic factor for both PFS and OS in Len-exposed patients. In this real-world Len-exposed cohort, Len-refractory patients receiving 1L Len experienced poorer survival outcomes than non-Len-refractory patients, highlighting the unmet need in this patient population which has driven the development of novel therapies. Limited real-world data exist to guide second-line (2L) treatment strategies for multiple myeloma patients who become refractory to lenalidomide (Len) in first-line therapy. This Greek MM centre study reports poor 2L survival outcomes in Len-refractory patients versus patients non-refractory to Len. Proteasome inhibitor-based and triplet regimens were frequently used in Len-refractory patients and yielded longer survival rates than other regimens.