Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)
Category: Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)
Efficacy and Safety of Biweekly/Weekly Ixazomib-Dexamethasone Maintenance Therapy in Chinese Patients with Newly Diagnosed Multiple Myeloma: A Multi-center Study
Xiaoyan Han, The First Affiliated Hospital, Zhejiang University School of Medicine
Chief physician
The First Affiliated Hospital, Zhejiang University School of Medicine
Ixazomib, the first oral proteasome inhibitor, has shown efficacy as maintenance therapy in newly diagnosed multiple myeloma (NDMM) patients in clinical trials. However, real-world data on ixazomib-dexamethasone (Id) maintenance in this population, particularly comparing weekly and biweekly dosing, remain limited. We conducted a multicenter real-world study to evaluate the efficacy and safety of Id maintenance in Chinese NDMM patients, including those on a biweekly ixazomib schedule.
Methods:
This retrospective study included NDMM patients from 11 tertiary centers who received ≥3 cycles of Id maintenance, from Nov 1, 2018, to Dec 1, 2022. All had achieved at least partial response (PR) after 6-8 cycles of primarily bortezomib-based induction. The primary end-point was progression-free survival (PFS). The dosing schedule of ixazomib (4 mg on days 1, 8, and 15 of a 28-day cycle [I1d] or 4 mg on days 1 and 15 of a 28-day cycle [I2d]) was determined by the treating physician based on baseline physical condition and toxicity.
Results:
A total of 168 patients were analyzed. Median age was 63 (IQR 59-73). Sixty-one of 112 (54.5%) patients had gain/amp(1q) and 35 (20.8%) had renal insufficiency. A majority of patients (111, 66.1%) had not undergone ASCT.
At a median follow-up of 29.5 months, the median PFS was 24.4 (95% CI 19.2-38) months. Twenty-five (14.9%) were deceased and the median overall survival was 59 (95% CI 59-NA) months. In subgroups with amp/gain(1q), renal insufficiency, and ASCT, the median PFS was 19.2, 19.6, and 29.9 months, respectively; differences were not statistically significant (all P>0.05). Notably, patients with MRD+ before maintenance had a significantly inferior PFS compared with those with MRD- (10.8 vs. 24.4 months, P=0.002). MRD status remained an independent predictor of PFS in the multivariate analysis (HR 2.28 [1.19-4.36], P=0.01).
The I1d cohort (n=118) had more frequent prior exposure to lenalidomide versus the I2d cohort (n=47) (54.2% vs. 21.3%, P< 0.001). Median PFS was comparable between I2d and I1d (25.5 vs. 21.7 months, P=0.4), and remained so after sIPTW adjustment (25.5 vs. 19.5 months, P=0.45). In the elderly, amp/gain(1q), and ASCT subgroups, there was no significant difference in PFS between the two regimens (all P>0.05).
Common adverse events (AEs) included thrombocytopenia (33.3%) and gastrointestinal symptoms (23.8%). The I2d group had fewer GI AEs than I1d (10.6% vs. 28.9%, P=0.02).
Conclusions:
In the real-world setting, Id maintenance therapy provides sustained survival benefits for NDMM patients. The biweekly ixazomib schedule achieves similar PFS with reduced toxicity, supporting its feasibility. MRD status remains a critical prognostic marker during maintenance therapy.