According to data presented at the 63rd Annual American Society of Hematology Meeting, combination ixazomib and daratumumab, without dexamethasone, was tolerable in elderly and frail patients with relapsed/refractory multiple myeloma (RRMM).

“Frail patients with multiple myeloma have an inferior outcome, especially in the relapse setting. This adverse prognosis is mainly related to a high discontinuation rate due to treatment related adverse events. The aim of this phase 2 study is to evaluate efficacy and tolerability of Ixazomib-Daratumumab (I-Dara) without dexamethasone in elderly frail patients with relapsed myeloma,” explained Margaret Macro, Institut d’Hématologie de Basse Normandie, Centre Hospitalier et Universitaire de Caen, France, and colleagues.

With this in mind, researchers enrolled ixazomib-daratumumab naive RRMM patients (1-2 prior therapy) with a frailty score of s ≥2 by IMWG score and FIRST proxy score (Leukemia).

The primary end point was ≥ very good partial response rate at one year; the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), OS, and toxicity according to NCI-CTCAE version 5.0.

Of the 52 patients screened during this trial, 44 were included from March 2018 to May 2021; 28 were at first relapse and 16 at second relapse. Additionally, 38 (86%) patients were exposed to prior bortezomib, and 8 (18%) were previously refractory to lenalidomide; all patients had a frailty score ≥2. 

Furthermore, 11 (32%) patients harbored high-risk cytogenic, including 3 with t(4;14) and 8 with del17p. The median duration of treatment among the 23 patients whose treatment was ongoing was 6 months (0-27), while the median duration among the 21 patients who stopped treatment was 7 months (0-21). The ORR, including minimal response, was 86% in patients with ongoing treatment and 71% in patients who stopped treatment, while the ≥VGPR rate was 33% and 6%, respectively.

There were 28 treatment-related adverse events (AEs) that occurred in 24 (54%) patients, the most common being thrombocytopenia (5), other cytopenias (4), infection (4), and gastrointestinal disorders (2). Fourteen of the 28 were serious AE’s, including 1 bronchospasm, 1 acute respiratory failure, and 2 ixazomib overdoses. A total of 13 patients had progressive disease, and six patients died during this study due to Daratumumab-related bronchospasm (D1C1); Ixazomib-related overdose (C2); progressive disease (C2 and C4), sepsis (C1 and C2). 

“These preliminary results show a favorable safety profile of ixazomib and daratumumab combination, without dexamethasone, in this specific population of very elderly frail patients with RRMM and high risk cytogenetic for almost one third of them. Efficacy results will be analyzed when the 50 patients will be enrolled in the study and evaluable for the primary endpoint,” concluded Dr Macro et al.—Alexandra Graziano
 

Marco M, Touzeau T, Mariette C, et al. Ixazomib and Daratumumab without Dexamethasone (I-Dara) in Elderly Frail RRMM Patients. a Multicenter Phase 2 Study (IFM 2018-02) of the Intergroup Francophone Du Myélome (IFM). Presented at: the 63rd ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 83.