Real-World Progression-Free Survival and Healthcare Resource Utilization Associated with Daratumumab Use in Transplant-Ineligible Multiple Myeloma Patients in Italy

Valentina Perrone,1 Gregorio Barilà,2 Luca Franceschini,3 Giuseppe Mele,4 Stefania Mazzoni,1 Maria Cappuccilli,1 Margherita Andretta,5 Marcello Bacca,6 Fausto Bartolini,7 Antonietta Barbieri,8 Alessandra Blasi,9 Alessandro Chinellato,10 Stefania Dell’Orco,11 Fulvio Ferrante,12 Renato Lombardi,13 Daniela Mancini,6 Romina Pagliaro,14 Arrigo Paciello,15 Maurizio Pastorello,16 Cataldo Procacci,17 Daniela Ricciardulli,14 Loredana Ubertazzo,18 Paola Valpondi,19 Alberto Zucchi,20 Luca Degli Esposti1 1CliCon S.r.l. Società Benefit, Health Economics & Outcomes Research, Bologna, Italy; 2Hematology Unit, San Bortolo Hospital, Vicenza, Italy; 3Lymphoprolipherative Diseases Unit- Oncohaematology Department, Policlinico Tor Vergata, Rome, Italy; 4Hematology Unit, “A. Perrino” Hospital, Brindisi, Italy; 5Territorial Pharmaceutical Care Unit, Local Social and Health Authority No. 8 Berica, Vicenza, Italy; 6Direction of Planning and Management Control, Local Health Authority of Brindisi, Brindisi, Italy; 7Pharmaceutical Department, Local Health Authority Umbria 2, and Coordination of the Umbria Region Steering Committee on Pharmaceutical Governance, Terni, Italy; 8Territorial Pharmaceutical Service Complex Unit, Local Health Authority of Vercelli, Vercelli, Italy; 9Hospital Pharmacy Complex Unit, Local Health Authority Roma 3, Rome, Italy; 10Hospital Pharmacy Complex Unit, Local Social and Health Authority No. 3 Serenissima, Mestre (Venice), Italy; 11Territorial Pharmaceutical Service Complex Unit, Local Health Authority, Albano Laziale (Rome), Italy; 12Department of Diagnostics and Pharmaceutical Care, Local Health Authority of Frosinone, Frosinone, Italy; 13Territorial Pharmaceutical Service, Local Health Authority of Foggia, Foggia, Italy; 14Territorial Pharmaceutical Service Complex Unit, Local Health Authority Roma 5, Rome, Italy; 15Territorial Pharmaceutical Service Complex Unit, Health Protection Agency of Bergamo, Bergamo, Italy; 16Pharmaceutical Department, Public Agency for Personal Care Services of Palermo, Palermo, Italy; 17Pharmaceutical Department, Local Health Authority of Barletta Andria Trani (BAT), Andria, Italy; 18Territorial Pharmacy Complex Unit, Local Health Authority, Civitavecchia (Rome), Italy; 19Territorial Pharmaceutical Care Complex Unit, Local Social and Health Authority No. 7 Pedemontana, Bassano del Grappa (Vicenza), Italy; 20Complex Operational Unit of Epidemiology Service, Health Protection Agency of Bergamo, Bergamo, ItalyCorrespondence: Valentina Perrone, CliCon S.r.l. Società Benefit - Health, Economics & Outcomes Research, Via Murri 9, Bologna, 40137, Italy, Tel +39 (0)544 38393, Fax +39 (0)544 212699, Email [email protected]: This study evaluated real-world clinical and economic outcomes associated with daratumumab-based regimens in patients with multiple myeloma (MM) ineligible for autologous stem cell transplantation (ASCT) in Italy. Differences in healthcare resource use according to daratumumab administration route (intravenous vs subcutaneous) were also explored.Methods: A retrospective observational analysis was conducted using administrative healthcare databases from Italian Local Health Units covering ~12 million individuals (2018– 2023). Patients with MM receiving daratumumab in first-line (1L) or second-line (2L) therapy were included. Real-world progression-free survival (rwPFS), defined as time to treatment switch or death, was used as a proxy endpoint for disease progression, and healthcare resource utilization were compared between treatment regimens. Propensity score weighting was applied to to improve comparability between treatment groups. Direct healthcare costs captured in administrative databases were analyzed from the perspective of the Italian National Health System.Results: Among 790 non-ASCT MM patients, 344 received 1L DaraRd and 413 received 2L DaraRd. In the 1L setting, median rwPFS was not reached for DaraRd and was 25.7 months for Rd (p=0.011). In 2L, median rwPFS was 42.9 months for DaraRd versus 19.1 months for Rd (p < 0.001). In 1L, DaraRd was associated with lower hospitalization costs compared with Rd for both all-cause (€ 4324 vs € 7971) and MM-related (€ 2862 vs € 6693) admissions. In 2L, differences in hospitalization costs were smaller and not statistically significant.Conclusion: In this real-world analysis, daratumumab-based regimens were associated with longer rwPFS compared with Rd among transplant-ineligible MM patients, in both 1L and 2 L settings. In 1L treatment, these outcomes were accompanied by lower hospitalization costs. Given the retrospective design and the use of administrative healthcare data, these findings should be interpreted with caution, but they contribute to the growing body of real-world evidence on treatment outcomes and resource utilization in routine clinical practice.Keywords: daratumumab, dexamethasone, healthcare costs, healthcare resource utilization, lenalidomide, multiple myeloma, real-world evidence, subcutaneous administration