Efficacy of Isa-Pom-Dex Therapy in Double Refractory Multiple Myeloma (MM) Patients in Real Clinical Practice
Authors: Soloviev Maxim , Mendeleeva Larisa , Soloveva Maiia , Pospelova Tatiana Ianovna , Skvortsova Natalia , Volodicheva Elena , Zhelnova Evgenia , Kirillova Elena , Kiseleva Marina , Chuprakova Alina , Bahtina Varvara , Kuchma Galina , Ochirova Oksana , Voloshin Sergey , Garifullin Andrey , Mitina Tatiana , Dudina Galina , Abramova Victoriya , Olkhovik Tatyana , Zakharova Marina , Usankin Ilya , Medvedeva Nadezhda , Ryabchikova Viktoria , Semenova Anastasiya , Kopylova Anna , Solovkova Natalya , Demchenkova Marina , Tsyganok Tatyana , Gammershmidt Yulia , Kuznetsova Olesya 
Published: December 2024

Background: Data from real-life clinical practice studies provide additional information on the efficacy of new antitumor therapy regimens, including in patients who meet exclusion criteria for clinical trials: patients with comorbidity, advanced stages, the elderly and weakness, low GFR, and those on hemodialysis.

Aims: to evaluate the effectiveness of the IsaPomDex triplet in MM patients in real clinical practice, to determine the parameters of OS.

Patients and Methods: From 2021 to 2024, the prospective study included 83 MM patients from 26 centers aged 38 to 85 years (median 63), who received the IsaPomDex triplet for the treatment of another relapse. Glomerular filtration rate &lt;60 ml/min was detected at the time of initiation of the isatuximab-based triplet in 17 (18%) patients, 2 of whom were on program hemodialysis. The median of previous therapy lines was 2 (1-6) - the majority of patients received bortezomib (99%) and lenalidomide (94%), daratumumab - 28%, carfilzomib 18%, pomalidomide - 10%, ixazomib - 8% and elotuzumab - 8%, auto-HSCT was performed in 43% of patients. The median time from diagnosis to initiation of isatuximab-based triplet therapy was 47 months (5-203). Treatment efficacy, outcomes (relapse, progression, death), and adverse events were analyzed. Survival curves were constructed using the Kaplan-Meier method. Statistical analysis was done using Statistica 10.

Results: Analysis of the use of IsaPomDex regimen in real clinical practice in 26 centers demonstrated that triplet therapy was characterized by achieving an overall response in 76%, renal response in 61% of cases. The median PFS was 13.5 months, when the triplet was prescribed in the second line the median PFS was not achieved, in the case of using the combination in the third line - 14.3 months. In the group of patients who did not receive daratumumab at previous stages, the median PFS was significantly higher and was 28 months vs 8 months (p &lt; 0.05). 3-year OS was 81%. Experience with the IsaPomDex regimen demonstrates good tolerability - the most common hematological AE was neutropenia - 70%, grade 4 - 17%. Discontinuation of isatuximab due to the development of AE was recorded in 2 cases (2%). The IsaPomDex combination was administered to 2 patients with stage 5 CKD who were receiving renal replacement therapy; no significant increase in the incidence of AEs was observed. In the group of patients with intraosseous components (n=46), IsaPomDex therapy was characterized by achieving a general response in 67% of cases, 12-month PFS was 48%, and 1-year OS was 76%.

Conclusion: The results of the study of real clinical practice on the use of IsaPomDex triplet for the treatment of relapsed MM showed data comparable to the ICARIA registration study on the frequency of achieving a response, duration of PFS and OS. At the same time, the effectiveness of the triplet was shown in elderly and weakened patients, with advanced stages and those undergoing renal replacement therapy.