Pomalidomide-Based Regimens with Monoclonal Antibodies As Salvage Therapy for Patients with Multiple Myeloma: Sardinian, Multicenter, Retrospective Clinical Practice Experience with 54 Cases Outside of Controlled Clinical Trials
Authors: Derudas Daniele , Podda Luigi , Murtas Andrea , Deiana Luca , Depau Cristina , Liguori Annamaria , Fozza Claudio , La Nasa Giorgio , Palmas Angelo D. 
Published: December 2024

Introduction: Pomalidomide represents the backbone for the treatment of relapsed/refractory Multiple Myeloma in combination with several agents as monoclonal antibodies and proteosome inhibitors. Since October 2020 three associations of Pomalidomide with monoclonal antibodies (Isatuximab, Daratumumab and Elotuzumab) have been available in Italy for the treatment of relapsed or refractory Multiple Myeloma (RRMM). The triplets Isatuximab -Pomalidomide-Dexamethasone (IsaPd) and Elotuzumab-Pomalidomide-Dexamethasone (EloPd) are licensed after two lines of therapy with lenalidomide and a proteosome inhibitor while Daratumumab association is available from second line of therapy. Here, we report preliminary efficacy and safety data for the combinations of monoclonal antibodies with Pomalidomide in a Sardinian study of RRMM patients as salvage therapy outside of controlled clinical trials. The primary objective of this study was to evaluate the toxicity profile and quality of respons e to EloPd, IsaPd and DaraPd administered as salvage therapy in a real-world setting.
Methods: The 3 cohorts included 54 patients with RRMM from 4 Sardinian centers who received at least one cycle of IsaPd (20 patients), EloPd (15 patients) or DaraPd (19 patients) as salvage therapy between February 2021 and June 2024.
Results: The median age of the 20 IsaPd-treated patients was 67.5 years (range 49-84 years), 74 years (range 59-82 years) for the EloPd cohort and 69 (36-81years) for DaraPd population; 50%, 80 and 53% were male, respectively (Table 1). The median number of prior therapies was 2 (range 2-4) for the IsaPd, 3 (range 2-7) for the EloPd and 2 (2-5) cohort; 13 (65%), 7 (46%) and 12 (63%) received prior autologous stem cell transplantation (ASCT), respectively. In the EloPd cohort 12 patients (80%) are more than 70 years and 66% shows a creatinine clearance less than 60 ml/min. Overall 4 patients out of 54 have a clearance creatinine ≤ 30 ml/min. Only 15 patients (28%) of the three cohorts started the treatments because of refractoriness.
The median number of courses of IsaPd administered to date was 5 (range, 1-29). The overall response rate (ORR) was 53%, with 3 stringent complete remissions (sCR) (16%) and 2 complete response (CR) (10%). The median time to first response was 1 month, while the median time to best response was 2 months. In the EloPd population, it was documented ORR of 60%, with 1 sCR (7%), 3 CR (20%), and 3 very good partial remissions (VGPRs) (20%). A median time to first response of 1 month was also recorded in this population, whereas the median time to best response was 2 months. The ORR in the DaraPd populations was of 58%, with 2 sCR (11%), 4 CR (21%), and 5 VGPRs (26%). Renal insufficiency and age &gt; 70 years had no significant impact on the likelihood of achieving a response in either population. A median time to first response of 1 month was also recorded in this population, whereas the median time to best response was 2 months.
In the IsaPd cohort, after a median follow-up of 8 months (range 1-26 months), 16 patients discontinued treatment, 14 due to disease progression, 1 due to toxicity, and 1 due to patient choice). Eleven patients died (9 patients from progressive disease, 1 from secondary acute myeloid leukemia and 1 for Hodgkin Lymphoma). Common grade 3 or 4 adverse events were thrombocytopenia (20%), neutropenia (45%), anemia (15%), and infection (15%). Infusion reactions occurred in only 2 patients (10%) and were grade 1 or 2 without treatment discontinuation. In the EloPd population, the median follow-up time was 8 months (range 3-25 months). Eight patients discontinued treatment, 7 for progression and 1 for toxicity: 3 died due to disease progression. Grade 3 or 4 adverse events were fatigue (18%), thrombocytopenia (18%), neutropenia (18%), anemia (36%), and infection (63%). The median follow-up in DaraPd population was of 9 months (range 1-16 months), 3 patients discontinued treatment, 1 due to disease progression, 1 due to toxicity, and 1 due to refractoriness). Only 1 patient died from progressive disease. Common grade 3 or 4 adverse events were neutropenia (21%), anemia (15%), and infection (15%), fatigue (53%).
Conclusions: Despite the limited number of cases, our preliminary real-world data confirm that the associations of Pomalidomide with monoclonal antibodies represent effective and safe therapies for RRMM patients, broadly consistent with results from controlled clinical trials.