ABSTRACT
Background: Comprehensive evaluation of new treatment regimens in RRMM patients both from physician's and patients' perspective is worthwhile. Aims: We aimed to evaluate clinical and patient-reported outcomes during IRd treatment as ≥ 2nd line in RRMM patients in a multicenter real-world evidence study. Methods: Adult patients with RRMM who have been assigned IRd as ≥2nd line treatment were enrolled in 18 centers of Russian Federation from April 2019 till May 2020. Treatment response was evaluated by IMWG 2011 criteria. For assessment of adverse events (AEs) NCI CTCAE v. 4.0 was used. Patients filled out RAND SF-36 and ESAS-R questionnaires at baseline, at 1 and 3 mos, and thereafter every 3 mos till 18 mos after IRd treatment onset. Statistical analysis of patient-reported outcomes was conducted using GEE with adjustment to age, gender and baseline quality of life (QoL). Duration of response (DOR), progression-free (PFS) and overall survival (OS) from the start of IRd treatment were evaluated using Kaplan-Meyer method. Results: In total, 40 patients with RRMM were enrolled into the study: median age - 64 years (range, 33-80), 35% males. Durie-Salmon stage at study entry: II/III - 40/60%, ECOG status 0/1 - 70%, 2/3 - 30%. Median time since initial MM diagnosis - 55 mos (range, 2.0-99.0). Median number of lines of prior therapy - 3 (range, 1-7). Comorbidities were revealed in 65% patients;median Charlson Comorbidity index - 2 (range, 0-5);95% patients had bone complications. The median duration of IRd treatment - 7.5 mos (IQR, 3.9-18.0). Two-thirds of the patients (28/39) responded to therapy. The overall response rate was 46.2% (95%CI: 30.6-61.8), median DOR - 16.3 mos (95%CI: 15.4-17.3). Among them 3 patients achieved complete response, 1 - stringent complete response, 2 - very good partial response, 12 - partial response. Ten patients had minor response. Clinical benefit rate - 71.8% (95%CI: 57.7-85.9). Six patients (15.4%) had stable disease and 4 (10.3%) progressed upon therapy. Median PFS was 10.6 mos (95%CI: 6.3-16.3). During the entire period of the study 5 deaths were registered: 3 were related to progression, 2 - because of COVID-19. Median OS was not reached. One-year OS rate was 85.2% (95%CI: 71.0-99.0). AEs were revealed in 55% patients: grades 1-2 AEs - 15 patients;grades 3-4 AEs - 7 patients;SAEs - 3 patients (neurological toxicity, gastric bleeding, hypotension and diarrhea). Baseline QoL was dramatically impaired by the majority of SF- 36 scales;42% patients experienced severe/critical QoL impairment. At baseline all the patients experienced symptoms;85% with moderate-to severe symptoms (≥4 scores on the scale from 0 to 10). The most prevalent and severe symptoms were tiredness (98%), drowsiness (90%), pain (82%) and shortness of breath (80%). During IRd treatment QoL was stable or improved. Physical and role physical functioning, general health, vitality and mental health significantly improved as compared to baseline (GEE, p<0.05). Twice increase of Integral QoL Index was observed - 0.27 at baseline vs 0.48 at 18 mos (p<0.05). Severity of pain, tiredness and nausea meaningfully decreased during IRd treatment as compared to baseline (GEE, p<0.05). Total ESAS-R score decreased by 10 points at 18 mos of therapy as compared to baseline - 31 vs 21 (GEE, p<0.05). Summary/Conclusion: In summary, results obtained in a real-world evidence study confirmed RCTs data that IRd regimen is an effective treatment in RRMM patients. This treatment is accompanied with definite improvement of QoL. Our results demonstrate benefits of IRd, both from physician's and patient's perspective.