Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World "POWERFUL" Study.

Evangelos Terpos,Eirini Katodritou,Magdalini Dadakaridou,Chrysavgi Lalayanni,Evdoxia Hatjiharissi,Anastasia Pouli,Christos Georgopoulos,Argiris Symeonidis,Eurydiki Michalis,Panagiotis Repousis,Emmanouil Spanoudakis,Christos Poziopoulos,Maria Gavriatopoulou,Georgios Vassilopoulos,Panagiotis Zikos ,Helen Α Papadaki ,Vasiliki Pappa ,Theodora Assimakopoulou ,Gerassimos A Pangalis ,Marie‐Christine Kyrtsonis ,Kiki Karvounis‐Marolachakis ,Ioannis Ntanasis‐Stathopoulos

doi:10.3390/jcm10071509

Abstract

The “POWERFUL” multicenter, retrospective, and prospective study investigated the effectiveness of pomalidomide plus low-dose dexamethasone (POM/LoDex) therapy in relapsed/refractory multiple myeloma in routine care in Greece. Ninety-nine eligible adult patients treated with POM/LoDex according to the approved label after having received ≥2 prior therapies, including lenalidomide and bortezomib, were consecutively enrolled between 16 November 2017 and 21 February 2019 in 18 hematology departments. Fifty patients (50.5%) started POM/LoDex as third-line treatment. During the treatment period (median: 8.3 months; range: 0.3–47.6 months), the median POM dose was 4 mg/day, and 31.3% of the patients received additional antimyeloma agents. The overall response rate was 32.3%. During a median follow-up period of 13.8 months (Kaplan–Meier estimate), the median progression-free survival (PFS) was 10.5 months (95% CI: 7.4–14.4). The PFS was not significantly different between patients receiving POM/LoDex in the third versus later line of therapy, nor between patients receiving concomitant antimyeloma therapy versus POM/LoDEx doublet. During the prospective safety data collection period (median: 7.6 months) among patients with prospective follow-up (N = 75), POM-related adverse event incidence rate was 42.7% (serious: 18.7%; grade ≥ 3 hematological POM-related adverse events: 8.0%). Only neutropenia (13.3%) was reported at a frequency ≥10%. In conclusion, in this real-world study, POM/LoDex displayed a long PFS with no new safety signals emerging.

Highlights

Multiple myeloma (MM), a hematological malignancy associated with significant morbidity and mortality, is characterized by clonal plasma cell expansion in the bone marrow, presence of monoclonal immunoglobulin in the serum or urine, lytic bone lesions, hypercalcemia, renal insufficiency, anemia, and immunodeficiency
10%, we considered 100 patients to be adequate in order to ensure the aforementioned sample size for the final statistical analysis
In the present real-world study conducted in Greece, POM/LoDex demonstrated a long progression-free survival (PFS) when administered to patients with RRMM and at least two prior lines of therapy

Summary

Introduction

Multiple myeloma (MM), a hematological malignancy associated with significant morbidity and mortality, is characterized by clonal plasma cell expansion in the bone marrow, presence of monoclonal immunoglobulin in the serum or urine, lytic bone lesions, hypercalcemia, renal insufficiency, anemia, and immunodeficiency. Effective treatment of early relapses with therapeutic approaches that provide direct tumoricidal effects and suppress residual disease via immune mechanisms of action is critical in order to delay the onset of subsequent relapses [7,8]. Pomalidomide (POM), along with thalidomide and lenalidomide (LEN), belongs to the class of IMiDs. The drug has pleiotropic functions, via induction of myeloma cell apoptosis, inhibition of angiogenesis, and immunomodulation, and it targets tumor cells, and the bone marrow microenvironment [9]. All three IMiDs exert their activity by binding to cereblon (CRBN), a protein component of the CRL4 E3 ligase complex [10], inducing its interaction with the transcriptional factors Aiolos and Ikaros [11]

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