Outcomes of Newly Diagnosed Multiple Myeloma Patients Requiring Dialysis

Introduction:

Renal impairment (RI) is a common complication in newly diagnosed multiple myeloma patients (NDMM) and ~1-5% patients require dialysis which is associated with significant morbidity and risk factor for early death. Clinical data, regarding outcomes and clinical course in these patients are limited, as they are excluded from clinical trials. Few prospective studies have evaluated the impact of high cut-off filters and bortezomib-based regimens but real-world data, especially in the changing treatment landscape are limited.

Aim: To assess patterns of renal responses and determinants of outcomes in patients with NDMM who are dialysis-dependent at disease presentation.

Methods: We analysed the outcomes of 73 consecutive NDMM with RI requiring dialysis, managed and treated in the Department of Clinical Therapeutics, Athens, Greece from January 2010 to December 2023.

Results: Median age of the cohort was 69 years (32-87), 52% had high-risk cytogenetics, median serum involved free light chain (sFLC) level was 8,800 mg/L (8,5-50,000), 49% had elevated serum LDH, 39% serum albumin < 3.5 mg/dl and 34% serum calcium ≥ 11 mg/dl. Almost all patients (n=70) received induction therapy with bortezomib-based regimens, 19% received doublet, 71% triplet and 10% quadruplet combinations while 12% received an anti-CD38 monoclonal antibody. Median follow up was 37.2 months (0.4-141 months) and during this period, 31 patients (42.5%) achieved dialysis independence. Median time to dialysis independence was 52 days (2-247 days). Ten (14%) patients underwent ASCT/ HDM, 8 achieved dialysis independence, 4 prior to and 4 following ASCT/HDM. In univariate analysis higher serum calcium was associated with dialysis independence (OR: 1.3, 95% CI 1.035-1.655, p=0.025). Older age decreased the probability of achieving dialysis independence (OR: 0.922, 95% CI 0.878-0.969, p=0.001) and patients <65 years were 6 times more likely to achieve dialysis independence (OR 6.07 95% CI 2.07-17.8, p=0.001). Among other baseline variables, serum albumin, urea, R-ISS (2 or 3), R2-ISS (3 or 4), FLC type, involved sFLC level or high-risk cytogenetics were not associated with dialysis independence. In terms of hematologic response, at 1 month landmark, patients in ≥PR were more likely to achieve dialysis independence vs patients in <PR (OR 3.67, 95% CI 1.049-12.86, p=0.042). The depth of response also affected dialysis independence (1month landmark): patients in ≥VGPR were 4.63 times more likely to achieve dialysis independence vs patients in PR (OR 4.63, 95% CI 1.13-18.9, p=.033); however, PR vs no response (NR) did not improve renal response rates (OR 1.83, 95% CI 0.22-15.33, p=0.58). Overall, 55.8% of patients with VGPR/CR vs 33.3% with PR vs 21.4% with NR achieved dialysis independence. Quadruplet combinations (with an anti-CD38 antibody) did not increase the rate of dialysis independence compared to triplet combinations (33.3% vs 44.3%, p=0.723). Dialysis independence rate was 44% in patients who received triplets/quadruplets vs 36% in patients who received doublets (p>0.05). In multivariate analysis at 1-month landmark, younger age was the most important prognostic factor for dialysis independence (p=0.018, HR 0.937 95% CI 0.89-0.99), there was a trend for hematologic response (p=0.124, HR 2.99, 95% CI 0.740-12.12) while hypercalcemia did not retain its prognostic value. Median OS was longer in patients who achieved dialysis independence compared to those who did not (36 months vs 13.3 months, p=0.085). Among patients who achieved dialysis independence, 1-year and 2-year OS (1-month landmark analysis) was 80% and 65% respectively vs 63% and 47% for patients who remained dialysis dependent. Early mortality (≤2 months) in patients with dialysis independence was low at 3.2% vs 28.6% among those who remained dialysis dependent (OR 0.083, 95% CI 0.01-0.682, p=0.020).

Conclusion: Without the use of any special filters, 42.5% of NDMM who require dialysis at diagnosis can achieve dialysis independence. Younger age, rapid and deep hematologic response and the presence of hypercalcemia as a treatable nephrotoxic factor are significant determinants. Dialysis independence decreases the probability of early death and is associated with longer survival and better quality of life. More data are needed for the evaluation of bortezomib plus anti-CD38 quadruplet combinations for patients with NDMM and severe RI.

Fotiou:Sanofi: Honoraria; Janssen: Honoraria. Gavriatopoulou:Genesis Pharma: Honoraria; Karyopharm: Consultancy; Amgen: Consultancy; Beigene: Research Funding; AbbVie: Honoraria; Janssen Cilag: Honoraria; Cellectar Biosciences: Research Funding; BMS: Research Funding; GSK: Consultancy, Honoraria; Integris: Honoraria; Takeda: Consultancy, Honoraria; Swixx: Honoraria. Ntanasis-Stathopoulos:Janssen-Cilag: Honoraria; AstraZeneca: Honoraria; Cellectar Biosciences: Research Funding. Migkou:Janssen Cilag: Honoraria; GlaxoSmithKline: Honoraria. Terpos:GSK: Honoraria, Research Funding; EUSA Pharma: Honoraria, Other: Travel expenses; AstraZeneca: Honoraria, Other: Travel expenses; BMS: Honoraria; Amgen: Honoraria, Other: Travel expenses, Research Funding; Janssen: Honoraria, Research Funding; Menarini/Stemline: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria, Other: Travel expenses, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria; Antengene: Honoraria, Research Funding; Swixx: Honoraria. Dimopoulos:GSK: Honoraria; TAKEDA: Honoraria; REGENERON: Honoraria; MENARINI: Honoraria; BMS: Honoraria; JANSSEN: Honoraria; BEIGENE: Honoraria; SWIXX: Honoraria; ASTRA ZENECA: Honoraria; SANOFI: Honoraria; AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kastritis:Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria; Genesis Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.