Serologic follow-up in patients with multiple myeloma without repeated bone marrow studies: a single-institution...

Assessment of measurable residual disease (MRD) in multiple myeloma (MM) often relies on repeated bone marrow evaluations, which are invasive, costly, and not universally accessible. Alternative monitoring approaches based on routinely available laboratory tests may provide clinically relevant prognostic information.

To evaluate whether longitudinal follow-up based exclusively on serologic monitoring can predict survival outcomes in a real-world cohort of patients with MM.

This retrospective single-center study included 88 consecutive patients diagnosed with MM between 1999 and 2024. All patients underwent bone marrow evaluation at diagnosis and were subsequently monitored using serial serum protein electrophoresis (SPEP) and immunofixation (IF), with serum free light chain (sFLC) assays when available. Serologic undetectability was defined as negative SPEP/IF together with normalization of the $\kappa /\lambda$ sFLC ratio. Patients with missing sFLC assays were conservatively analyzed in the serologically positive cohort. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier methods, log-rank testing, and univariable Cox proportional hazards models, taking into account potential guarantee-time (immortal-time) bias associated with post-baseline response endpoints.

Overall, 52 patients (59.1%) achieved disappearance of the monoclonal band on SPEP/IF. Twenty-nine patients (33.0%) met all criteria for complete serologic undetectability. Achievement of serologic undetectability was associated with a significantly lower risk of death (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.19-0.91; $p=0.0483$) and significantly longer PFS (HR 0.195, 95% CI 0.091-0.418; $p=0.0028$). Disease progression or relapse occurred in 28 patients overall. Among patients who achieved serologic undetectability, those undergoing autologous stem cell transplantation (ASCT) showed a numerical trend toward improved outcomes; however, differences did not reach statistical significance due to sample size constraints.

These findings suggest that sustained serologic clearance of monoclonal protein reflects deeper disease control and may serve as a clinically meaningful prognostic marker of treatment response. In resource-limited settings or centers where serial bone marrow-based MRD assessment is impractical, comprehensive serologic monitoring offers a feasible, non-invasive alternative for longitudinal disease evaluation.

In routine clinical practice, achievement of serologic undetectability defined by standard laboratory assays was associated with superior OS and PFS. These results support the prognostic value of accessible serologic monitoring strategies when repeated bone marrow-based MRD evaluations are not feasible.