Association Between Immunoparesis and Treatment Outcomes of Patients With Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Although immunoparesis occurs in up to 80% of patients with newly diagnosed multiple myeloma (NDMM), evidence regarding its prognostic impact remains unclear. Using a prepublished protocol (CRD42022308687), we searched seven bibliographic databases from inception to February 2023 for studies reporting the impact of immunoparesis on outcomes among adults with NDMM. The outcomes of interest were overall survival (OS), progression free survival (PFS) and infection risk. Of 5175 studies screened, 7 studies involving 6091 patients were included. Immunoparesis was not associated with worse OS (pooled hazard ratio 1.30; 95% CI, 0.91-1.84; P-value .11). However, immunoparesis was associated with a significantly worse PFS (pooled hazard ratio 1.42; 95% CI, 1.11-1.82; P-value .013). Infection rates were not uniformly reported precluding meta-analysis. Visual examination of funnel plot revealed possible publication bias. Our findings suggest that immunoparesis did not have a detrimental impact on OS but was associated with a significantly shorter PFS. Background: Immunoparesis, defined as suppression of uninvolved polyclonal immunoglobulins, occurs in up to 80% of patients with newly diagnosed multiple myeloma (NDMM). Infections are the second most common cause of mortality in this population, yet evidence regarding prognostic impact of immunoparesis in NDMM remains unclear. Materials and Methods: Using a prepublished protocol (CRD42022308687), we searched seven bibliographic databases from inception to February 2023 for studies reporting the impact of immunoparesis on clinical outcomes among adults with NDMM. The primary outcome of interest was overall survival (OS) and secondary outcomes were progression free survival (PFS) and infection risk. Effect sizes were quantified in terms of hazards ratio (HR) and pooled across studies using a random effects restricted maximum likelihood method. Heterogeneity was assessed using Cochran Q and the I2 2 statistic. Publication bias was assessed using contour enhanced funnel plots. Results: Of 5175 studies screened, 7 studies involving 6091 patients met our search cr iter ia. Immunoparesis was not associated with worse OS (pooled hazard ratio 1.30; 95% CI, 0.91-1.84; P-value .11), with significant heterogeneity among the studies (I2 = 72.9%; Cochran's Q P-value .003). However, immunoparesis was associated with a significantly worse PFS (pooled hazard ratio 1.42; 95% CI 1.111.82; p value 0.013), with moderate heterogeneity (I2 statistic = 51%; Cochran's Q P-value .056). Infection rates were not uniformly reported precluding meta-analysis. Visual examination of funnel plot revealed the possibility of publication bias. Conclusion: Overall, our findings suggest that immunoparesis did not have a detrimental impact on OS, but was associated with a significantly shor ter PFS. Fur ther studies are needed to understand the complexity of immune system perturbations in NDMM.