Quality of Life and Efficacy of Triplet IxaRd Therapy in Relapsed/Refractory Multiple Myeloma: Results of a Multi-Center Pilot Real-World Study
Authors: Ionova T.I. , Vinogradova O.Yu. , Kochkareva Yu.B. , Markova E.E. , Kaplanov K.D. , Shirokova M.N. , Shelekhova T.V. , Levanov A.N. , Kopylova A.V. , Li O.Yu. , Mitina T.A. , Rukavitsyn O.A. , Simashova P.I. , Anchukova L.V. , Babich E.N. , Volkova S.A. , Dasheeva D.B. , Demchenkova M.V. , Dubov S.K. , Esenina T.V. , Ivanova L.E. , Kravchuk T.L. , Rimashevskaya E.V. , Savinova M.T. , Saraeva N.O. , Porfirieva N.M. , Nikitina Tatyana Pavlovna , Ptushkin V.V. 
Published: July 2022

Aim. To study quality of life (QoL) indicators and symptom profile as well as treatment satisfaction of patients with relapsed/refractory multiple myeloma (r/r MM) on triplet therapy based on ixazomib combined with lenalidomide and dexamethasone (IxaRd); to assess efficacy and safety of IxaRd protocol in real-world clinical practice. Materials & Methods. The study enrolled 40 patients with confirmed r/r MM diagnosis, aged > 18 years, at 18 Russian health care institutions. They received at least one line of prior therapy and were IxaRd-eligible. Clinical and QoL indicators were assessed according to the RAND SF-36, and symptoms were evaluated using the ESAS-R questionnaire prior to IxaRd therapy and in 1, 3, 6, 9, 12, 15, and 18 months after its start. Besides, patients filled out checklists for assessment of treatment satisfaction at all time-points after therapy onset. The analysis of clinical IxaRd efficacy included assessment of treatment response by IMWG 2011 criteria, as well as response duration, overall survival (OS), and progression-free survival (PFS). The analysis of IxaRd safety was based on reporting adverse events (AEs), including severe ones (SAEs). To analyze patient-reported QoL and symptom changes during follow-up, GEE was used. To determine clinically meaningful changes, an effect size was calculated. Results. The study included 40 r/r MM patients (mean age 63 ± 9 years, 65 % women). Median disease duration before IxaRd therapy onset was 55 months (range 2-99 months). 60 % of patients had IIIA/IIIB Durie-Salmon stage. With the median IxaRd duration of 7.5 months, clinical benefit rate was 71.8 %. Complete response was reported in 7.7 % of patients, stringent complete response in 2.6 % of patients, very good partial response in 5.1 % of patients, partial response in 30.8 % of patients, and minor response was achieved in 25.6 % of patients. Stable disease was reported in 15.4 % of patients, and disease progression was identified in 10.3 % patients, including immunochemical relapse in 1 patient. The median response duration was 16.3 months (95% confidence interval [95% CI] 15.4-17.3 months), the median PFS was 10.6 months (95% CI 6.3-16.3 months). The median OS was not reached; the 1-year OS after IxaRd therapy onset was 85.2 % (95% CI 71-99 %). AEs on IxaRd therapy were reported in 55 % of patients, SAEs were reported in 3 (7.5 %) patients. Positive QoL changes were observed on IxaRd therapy. QoL improvement was meaningful in terms of physical functioning, role-physical functioning, general health, vitality, and mental health, compared to baseline. Moreover, a considerable decrease of pain, fatigue, and nausea was revealed. On the whole, 87.5 % of patients were satisfied with the triplet IxaRd therapy. Conclusion. The results of the present pilot study demonstrate efficacy and safety of the triplet IxaRd therapy (all per os) in real-world clinical practice from r/r MM patients’ and physicians’ perspective. Our data testify to the importance of patients’ feedback in the evaluation of therapy efficacy.