[Renal response and prognosis of newly diagnosed patients with multiple myeloma with renal impairment applying VRD and autologous hematopoietic stem cell transplantation].

Objective

To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.

Methods

This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.

Results

Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min(-1)· (1.73 m(2)) (-1), n=160], mild [≥60 ml·min(-1)· (1.73 m(2)) (-1) to <90 ml·min(-1)· (1.73 m(2)) (-1), n=55], moderate [≥30 ml·min(-1)· (1.73 m(2)) (-1) to <60 ml·min(-1)· (1.73 m(2)) (-1), n=39], and severe impairment [<30 ml·min(-1)· (1.73 m(2)) (-1), n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence (P<0.05). Despite younger age (P=0.001) and higher transplant rates (P=0.041) in severe cases, overall response rates (ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups (P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5-4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min(-1)· (1.73 m(2)) (-1)], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13-0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment (P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2-65 months). Multivariate analysis identified 1q21+ (OR=3.58, 95% CI: 1.17-11.02, P=0.026) and light-chain subtype (OR=2.86, 95% CI: 1.08-7.69, P=0.036) as independent predictors of poor renal response.

Conclusion

VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.