Ixazomib, Lenalidomide, and Dexamethasone (IRd) Versus Ixazomib, Pegylated Liposomal Adriamycin, and Dexamethasone(IDd) in Elderly Frail Newly Diagnosed Multiple Myeloma with GA Score ≥2: A Prospective Multicenter Study

Introduction

Frailty patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and higher rate of treatment discontinuation due to complications, poor tolerance and compliance and lack of effective treatment. The aim of this study was to prospectively investigate the treatment tolerability, clinical outcomes and quality of life of the ixazomib based regimens in frail NDMM patients according to IMWG frailty index. This trail is registered at http://www.chictr.org.cn/index.aspx as chiCTR1900024917.

Methods

This prospective trail was an investigator initiate, multicenter, non-randomized controlled study which frail NDMM patients received 6-8 four-week induction cycles of ixazomib, lenalidomide and dexamethasone (IRd) and ixazomib, pegylated liposome adriamycin and dexamethasone (IDd), followed by matienance therapy of 4-week with ixazomib and dexamethasone (Id) until progression. Inclusion criteria were aged ≥ 65 years, IMWG GA score ≥ 2 or Mayo geriatric vulnerability scoring system defined as vulnerable. Main exclusion criteria were acute cardiovascular and cerebrovascular events. The primary endpoint was overall response rate (ORR) defined by having at least a partial response (≥PR). The secondary endpoints were progression free survival (PFS), overall survival (OS), adverse events (AE) and health-related quality of life (using the EORTC-QLQ C30).

Results

From July 2019 to December 2021, a total of 132 patients from 15 hospitals were enrolled of which 12 were excluded because of ineligibility and non-randomized assigned to receive IRd group (n=60) or IDd (n=60) according to doctor's estimated (Figure 1). The median age was 71 years range (65-88). All patients had a GA Index higher than 2 score, in which 27.5% were also defined fragile by Mayo criterion. The ORR was 83%, including 22 (19.6%) patients with a complete response (CR) and 45 (40.2%) with a very good partial response (VGPR). The ORR was 84.2% and 81.8%, CR was 26.3% and 17.2, VGPR was 36.8% and 43.6% of IRd and IAd group, respectively. After a median follow-up time of 22.9m (95% CI 18.9-26.9), the median PFS was 19.5m of all patients, 24.6m and 15.8 of IRd and IDd group, respectively. The median OS of all patients and IRd group was no reach, while 29.2m in IDd group (Figure 1). Four patients died in 60 days post enroll up because of pneumonia caused by bedridden.

Twenty-six and thirty-six patients did not process to maintenance therapy in IRd and IAd group, due to PD (14 in IRd and 16 in IDd), AE (6 in IRd and 7 in IDd), incompliance (5 in IRd and 9 in IDd) and early death (1 in IRd and 3 in IDd).

Cumulative grade 3 or higher hematological AEs occurred in 10/60 (16.7%) and 13/60 (21.7%), whereas grade ≥3 non-hematological AEs were reported in 25/60 (41.7%) and 46/60 (76.6%) patients. Most common non-hematological grade ≥3 AEs were infections (20.8%) and gastro-intestinal (13.3%). Only 1 patient experiencing PNP grade 3 (0.83%).

During induction, patients experienced a statistically and clinically significant improvement in GHS/QoL of both IRd and IAd group (p<0.0001). (Figure 1)

Conclusion The results of ORR and safety support the use of IDd or IRd as frontline therapy for fragile elderly MM patients, which also improves QoL. IDd was especially suitable for frail MM patients with renal dysfunction and thrombosis.

No relevant conflicts of interest to declare.