Clinical bottom line
Anti-CD38 monoclonal antibodies represent a promising therapeutic option for patients with refractory multiple myeloma-associated kidney disease, a condition often complicated by cast nephropathy and other renal impairments. Emerging clinical evidence suggests these agents may improve renal outcomes by targeting malignant plasma cells and modulating immune pathways implicated in kidney injury. However, data remain preliminary, and their renal-specific benefits and safety profiles warrant further validation in dedicated nephrology-focused studies (Kanbay et al., 2026; Yu et al., 2026).
What the evidence shows
Anti-CD38 monoclonal antibodies, such as daratumumab and isatuximab, have transformed multiple myeloma treatment by selectively targeting CD38-expressing plasma cells, leading to tumor burden reduction and immunomodulation (Selim et al., 2024; Shah et al., 2022). Kidney involvement in multiple myeloma, including cast nephropathy, light chain deposition disease, and amyloidosis, contributes significantly to morbidity and mortality. Recent mechanistic and clinical data indicate that anti-CD38 therapies may also confer renal benefits by decreasing free light chain production, thereby mitigating nephrotoxicity (Kanbay et al., 2026).
Kanbay et al. (2026) provide a comprehensive review of the mechanistic rationale supporting anti-CD38 use in kidney disease, highlighting evidence that these antibodies reduce circulating pathogenic light chains and may exert direct immunomodulatory effects on renal inflammation and fibrosis. Clinical series and observational cohorts report improved renal function and dialysis independence in subsets of patients treated with anti-CD38 agents, although these findings are largely derived from hematology-focused trials with renal endpoints as secondary or exploratory outcomes (Kanbay et al., 2026; Yu et al., 2026).
Treatment of patients refractory to initial anti-CD38 therapy remains challenging, with Tan et al. (2025) systematically reviewing salvage options and underscoring the need for novel combinations and sequencing strategies to optimize both hematologic and renal responses. Safety data from Thet et al. (2022) affirm that anti-CD38 antibodies are generally well tolerated, though infusion reactions and immunosuppression-related infections require monitoring, particularly in patients with compromised renal function.
Economic analyses, such as Lin et al. (2024), highlight the substantial cost implications of anti-CD38 regimens, which may influence access and utilization in nephrology practice.
Caveats and uncertainty
Despite encouraging signals, robust randomized controlled trials specifically evaluating anti-CD38 monoclonal antibodies for multiple myeloma-associated kidney disease are lacking. Most available data derive from oncology trials where renal outcomes are secondary, limiting definitive conclusions about efficacy and safety in nephrology populations (Kanbay et al., 2026; Yu et al., 2026).
Heterogeneity in patient characteristics, disease severity, and concomitant therapies complicates interpretation of renal response rates. The long-term impact on chronic kidney disease progression and dialysis dependency remains uncertain. Additionally, resistance to anti-CD38 agents can develop, necessitating alternative treatment strategies (Tan et al., 2025).
Safety concerns, including infection risk and potential effects on residual renal function, require ongoing vigilance. Economic considerations may also restrict widespread adoption without clear cost-effectiveness data in nephrology settings (Lin et al., 2024).
How this may change practice
For nephrologists managing refractory multiple myeloma patients with kidney involvement, anti-CD38 monoclonal antibodies offer a novel therapeutic avenue that may improve renal outcomes alongside hematologic control. Integration of these agents into multidisciplinary care models could enhance patient prognosis, particularly in those with cast nephropathy or rapidly progressive renal impairment.
Clinicians should remain cautious, balancing potential benefits against uncertainties and monitoring for adverse effects. Collaboration with hematology specialists is essential to optimize treatment sequencing and supportive care.
Future practice may incorporate anti-CD38 therapies earlier in the disease course for patients at high risk of kidney injury, pending confirmatory trials. Additionally, nephrologists should advocate for and participate in research to clarify renal-specific efficacy, safety, and cost-effectiveness.