Pomalidomide Plus Low Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World 'Powerful' Study
Authors: Terpos Evangelos , Repousis Panagiotis , Lalayanni Chrysavgi , Hatjiharissi Evdoxia , Assimakopoulou Theodora , Vassilopoulos George , Pouli Anastasia , Spanoudakis Emmanouil , Michali Evridiki , Pangalis Gerassimos , Poziopoulos Christos , Kyrtsonis Marie-Christine , Pappa Vassiliki , Symeonidis Argiris , Georgopoulos Christos , Zikos Panagiotis , Papadaki Helen A. , Dadakaridou Magda , Karvounis-Marolachakis Kiki , Patos Petros , Katodritou Eirini 
Published: November 2020

Introduction: Pomalidomide (POM) plus low-dose dexamethasone (POM/LoDex) is a standard of care for patients with relapsed/refractory multiple myeloma (RRMM), who have received ≥2 prior therapies, including lenalidomide (LEN) and bortezomib (BORT). In view of the limited real-world evidence on POM/LoDex effectiveness, this study aimed to provide insight into progression-free survival (PFS), response to treatment and drug utilization patterns in the routine clinical practice in Greece.
Methods: 'POWERFUL' (NCT03353545) was a non-interventional, multicenter, retrospective and prospective study of adult RRMM patients, initiated on POM/LoDex between 01-Jan-2016 and 28-Feb-2019 per the approved label. Patients who had received up to one POM/LoDex cycle were consecutively enrolled between 16-Nov-2017 and 21-Feb-2019 (prospective recruitment phase). One month prior to completion of this phase, aiming to facilitate recruitment of the target size, patients, whose treatment with POM/LoDex was ongoing but &gt;1 cycles had been received or for whom treatment was discontinued, were consecutively enrolled in reverse chronological order, based on POM/LoDex start date (retrospective recruitment). Patients were observed until the earliest point of disease progression (PD), death, informed consent (IC) withdrawal, treatment discontinuation for reason other than PD or start of next antimyeloma therapy, physician's decision, or last patient enrolled plus up to 12 months of treatment. IC or consent waiver for deceased subjects was obtained. Safety data were collected prospectively.
Results: Eligible patients (N=99; 75 with prospective and 24 with a purely retrospective follow-up) were recruited by 18 hematology departments. The median (IQR) observation period was 8.8 (4.2-15.4) months. Baseline patient characteristics are presented in Table 1. Fifty patients (50.5%) started POM/LoDex as third-line treatment. POM was initiated at 4 mg/day on days 1-21 every 28 days in 75.8% of the patients. A median of 8 (range: 1-38) cycles were received at a median POM dose of 4 mg/day (range: 1-4), over 8.3 (range: 0.3-47.6) months. The POM dose reduction and interruption rates were 28.3% and 59.6%, respectively. Of the patients, 37.4% were treated for ≥ one year. Treatment was discontinued in 81.8%, due to PD (56.8%), safety reasons (22.2%), death (6.2%), other reasons (9.9%), and due to loss of follow-up (4.9%).
The investigator-assessed overall response rate (≥partial response [PR]) was 32.3%; best response rates were: stringent complete or complete response (7.1%), very good PR (8.1%), PR (17.2%), minimal response (11.1%), stable disease (21.2%), PD (12.1%), and non-evaluable response (23.2%). Median time to response and duration of response in patients achieving ≥PR was 3.2 [95% confidence interval (CI): 2.6-3.6] and 15.8 (95%CI: 11.3-not reached) months, respectively. Over a Kaplan-Meier estimated median follow-up of 13.8 months, the median PFS was 10.5 months (95%CI: 7.4-14.4) [13.0 vs. 8.8 months for patients treated in the third vs. the fourth- and beyond line (log-rank p=0.494), and 13.0 vs. 8.8 months for patients treated with POM/LoDex only vs. those co-administered other antimyeloma agents (log-rank p=0.411)]. The estimated 6-, 12-, 24- and 36-month PFS rates were 70.3%, 48.3%, 20.1% and 12.0%, respectively. Multivariate Cox regression analysis of the impact of baseline characteristics on PFS indicated male sex [hazard ratio (HR)=2.08; 95%CI: 1.12-3.89; p=0.021] and higher than normal serum lactate dehydrogenase levels (HR=2.84; 95%CI: 1.39-5.81; p=0.004) as negative predictors of PFS.
Over a median safety data collection period of 7.6 months (range: 0.4-18.6), the POM-related adverse events (ADR) incidence rate in the safety-evaluable population (i.e., 75 patients with prospective follow-up) was 42.7% (73 events). Only neutropenia (13.3%) was reported at a frequency ≥10%. The serious ADR rate was 18.7%, whereas grade ≥ 3 hematological and non-hematological ADR rates were 8.0%, and 5.3%, respectively.
Conclusion: In this Real-World dataset from Greek centers, POM/LoDex, administered in the third-line and beyond setting of RRMM, displayed a longer PFS than in controlled clinical trials, which was not impacted by the treatment line and concurrent receipt of other antimyeloma agents. About one-third of patients achieved at least PR with an about 16-month response duration.

Disclosures
Terpos: Amgen: Honoraria, Research Funding; Sanofi: Honoraria; Celgene: Honoraria; Takeda: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding; BMS: Honoraria. Repousis:Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hatjiharissi:Roche: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Assimakopoulou:Genesis pharma SA: Research Funding. Vassilopoulos:Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding. Pouli:Genesis pharma SA: Research Funding. Spanoudakis:Genesis pharma SA: Research Funding. Michali:Takeda: Research Funding; Genesis pharma SA: Research Funding. Pangalis:Genesis pharma SA: Research Funding. Poziopoulos:Genesis pharma SA: Research Funding. Kyrtsonis:Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Pappa:Genesis pharma SA: Research Funding. Symeonidis:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GenesisPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; WinMedica: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Research Funding; Astellas: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi/Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Georgopoulos:Genesis pharma SA: Research Funding. Zikos:Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding. Papadaki:Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dadakaridou:Genesis pharma SA: Research Funding. Karvounis-Marolachakis:Genesis pharma SA: Current Employment. Patos:Genesis pharma SA: Current Employment. Katodritou:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theagenion Cancer Hospital: Current Employment; Takeda: Honoraria, Other: Expenses, Research Funding; Genesis Pharma: Honoraria, Other: Expenses, Research Funding; Abbvie: Research Funding; Karyopharm: Research Funding.