Abstract
Introduction: International recommendations are based on the absolute necessity of prescribing maintenance therapy (MT) after auto-HSCT in MM. However, the need for MT upon achieving MRD negativity and the possibility of de-escalating MT in case of sustained MRD (sMRD) negativity remain open questions.
Objective: to determine the survival rates of patients with MM who achieved MRD negativity after auto-HSCT, depending on the appointment of MT lenalidomide for a fixed duration of 1 year and sMRD negativity status.
Patients and methods: From December 2014 to December 2024, 196 patients with MM aged 26 to 66 years (median 54), who achieved MRD negativity after auto-HSCT, were included in a prospective randomized study. On the 100th day after auto-HSCT, to determine MRD, a bone marrow study was performed using 8-color flow cytometry using. MRD-negative status was determined by the detection of less than 20 clonal plasma cells among 2,000,000 leukocytes (<0.001%, detection limit - 10–5). After auto-HSCT, 76 patients (39%) were prescribed lenalidomide at a dose of 15 mg per day from days 1 to 21 with an expected fixed duration of 1 year, 120 patients (61%) were under observation without MT. MRD status was analyzed by flow cytometry once a year. A sMRD negativity status was established in the absence of aberrant plasma cells in the bone marrow for at least one year according to the results of two measurements. The observation period from the moment of auto-HSCT ranged from 9 to 122 months (median - 48 months). Survival curves were constructed using the Kaplan-Meier method. Statistical analysis was performed using the STATISTICA 10 and MedCalc 23.3.1 packages.
Results: During the observation period, 67 MM relapses were recorded, of which 27 (36%) were in the group of patients with MT and 40 (33%) in the group of patients who were not prescribed MT. The median PFS for the entire group was 73 months, 5-year PFS was 55%, 5-year OS was 87%, the median was NR. Regardless of the prescription of lenalidomide after auto-HSCT, the 5-year PFS rates were comparable and were 49% in the group with MT (median 81 months) and 59% in the group without MT (median 59 months) (p>0,05). The 5-year OS rates also did not differ significantly regardless of the prescription of lenalidomide after auto-HSCT and were 86% in the group with MT and 89% in the group without MT (p> 0,05). The assessment of sMRD negativity response for 12 months was performed in 188 patients included in the study, the remaining 8 patients did not reach the control period for the MRD assessment. In the group of patients who received lenalidomide after auto-HSCT, a sMRD negativity was recorded in 54 (72%) of 75 patients. In the absence of MT, a sMRD negativity response was documented in 88 (78%) of 113 patients. The median PFS in patients with sMRD negativity was significantly higher and amounted to 104 months versus 26 months in the group of patients in whom the MRD negativity response did not persist for 12 months (p<0.001).The 5-year OS was significantly higher in the group of patients maintaining a sMRD negativity response for at least one year and was 95% versus 70% in the group of patients who did not maintain a MRD negativity for a year (p<0.001). The median PFS in the group of patients with a sMRD negativity without MT after auto-HSCT was 104 months and was not achieved with the appointment of MT. In contrast, in the group of patients with loss of MRD negativity within 12 months after auto-HSCT, the median PFS with the appointment of MT was 31 months and 23 months in its absence after auto-HSCT. The analysis of OS also confirmed the high significance of sMRD negativity: regardless of the prescription of MT, with sMRD negativity remission, 10-year OS was 90%, the median was not reached versus 107 months in the group without MT and loss of MRD negativity and 79 months in the group with MT and loss of MRD-negativity (p<0.001). Multivariate Cox regression analysis confirmed that the most important factor is a sMRD negativity.Conclusion: When MRD negativity was achieved after auto-HSCT, the administration of MT with lenalidomide was not characterized by an improvement in PFS and OS compared to the group of patients who did not receive MT. Sustained MRD negativity remission lasting at least 12 months after auto-HSCT is the main prognostic factor characterized by an improvement in PFS and OS regardless of the administration of MT.
