Efficacy and Safety of Daratumumab Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients Treated in an Italian Real-Life Multi-Center Retrospecive Study
Authors: Bianco Rosario , Della Pepa Roberta , Leone Aldo , Fontana Raffaele , Rocco Stefano , Amendola Angela , Palmieri Salvatore , Esposito Daniela , Roccotelli Daniela , Delle Cave Giuseppe , Spatuzzi Maria Rosaria , Spisso Roberta , Cerchione Claudio , Barone Marialucia , Botta Cirino , Derudas Daniele , Selleri Carmine , Frigeri Ferdinando 
Published: December 2024

INTRODUCTION
Multiple Myeloma is a debilitating disease characterized by an unpredictable clinical and laboratorystic course. Despite advances in treatment options over the last decade, patients with multiple myeloma (MM) typically experience recurrent relapses. Although several treatments are available for relapsed/refractory patients, their efficacy is often limited, resulting in poor survival outcomes. This retrospective study examines the real-world efficacy and safety of Daratumumab (Dara) combined with pomalidomide (P) and dexamethasone (d) (DaraPd) as a salvage therapy for relapsed/refractory multiple myeloma (RRMM) patients outside of controlled clinical trials, in accordance to marketing approval.
PATIENT AND METHODS
A total of 49 RRMM patients from 10 italian centers were enrolled in the study after receiving at least two cycle of DaraPd as salvage treatment between February 2023 and July 2024. Patients included in the study had experienced relapse after at least one prior lines of therapy, which included immunomodulatory drugs (IMiDs) and a proteasome inhibitors (PIs) or were double refractory.
The treatment regimen consisted of Daratumumab s.c. (1800 mg) administered according to the recommended dosing schedule, pomalidomide at 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly.
Responders were defined as alì patients who achieve at least a partial remission (PR).
Of the 49 enrolled patients, 29 were males (59.2%), and 7 (14.1%) classified as stage III disease according to the Revisioned International Staging System (R-ISS). The median number of prior therapies was 2 (1-4), with 24.8% of patients exhibiting refractory disease. Additonally, 38.9% of patients had undergone autologous stem cell transplant (ASCT). Cytogenetic data from fluorescence in situ hybridation (FISH) analysis were available for 47 patients (95.9%), with 69.7% showing favorable cytogenetic profiles. In contrast, 30.3% classified as high-risk due to aberrations such as t(4;14), t(14;16), gain(1q21), t(11;14), and del(17p).
RESULTS AND COMMENTS
As of July 2024, all patients were evaluable for response.
The median number of DaraPd cycles administered was 11 (range 2-17).
The overall response rate (ORR) was 94% with 67% achieving a complete response or better. After a median follow-up of 12.5 months (range 1-17), disease progression or death occurred in 7 patients, resulting in a median progression-free survival (PFS) of 10.4 months. Univariate analyses indicated a shorter PFS for patients with elevated LDH (HR=1.8; P=0.004), high-risk cytogenetic abnormalities (HR=2.57; P&lt;0.0001), refractory disease (HR=1.52; P=0.02), R-ISS stage III (HR=2.48; P&lt;0.0001). Cox multivariable analysis identified high-risk cytogenetic abnormalities (HR=2.87; P&lt;0.0001) and elevated LDH (HR=2.35; P=0.003) as independent prognostic factors for PFS.
The cumulative 2-year-overall survival (OS) probability rate was 62.3%. with sognificant differences observed in Cox multivariate analysis for patients with high-risk high-risk cytogenetic abnormalities (HR=2.12; P=0.023), elevated LDH (HR=3.3; P=0.001) and creatinine clearance &lt;60 ml/min (HR=2.48; P=0.007),
The safety profile was acceptable, with 65% incidence of hematological adverse events (neutropenia and thrombocytopenia), wich were generally grade 1-2, and without an increase in infection rate.
In conclusion, this comprehensive real-world study confirms the safety and efficacy of DaraPd as a viable salvage therapy for patients with RRMM who have undergone at least one treatment regimens.
Further data are needed to better determine the appropriate line of therapy in which DaraPd should be incorporated into the treatmente algorithm for RRMM patients.