Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not yet been explored. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated according to immunoglobulin recovery at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression free, 88 patients (52%) showed immunoglobulin recovery and 81 (48%) did not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; Hazard Ratio: 0.45, 95%Confidence Interval: 0.31–0.66; P<0.001), and improved overall survival (11.3 vs. 7.3 years; Hazard Ratio: 0.45, 95%Confidence Interval: 0.27–0.74; P=0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: nine months and one year. In conclusion, the recovery of polyclonal immunoglobulins one year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival.
Summary
Immunoparesis is the suppression of normal polyclonal immunoglobulins and is present in most patients with newly diagnosed multiple myeloma (MM). The association of immunoparesis at diagnosis, and particularly its recovery along with treatment, with survival in patients ineligible for autologous stem‐cell transplantation (ASCT) has not been well established. This retrospective study evaluated the impact of immunoparesis in 431 patients diagnosed with MM, ineligible for ASCT, with a median overall survival of 36 months [95% confidence interval (CI): 31–40]. Immunoparesis was present in 81.2% of patients at diagnosis and was associated with a trend to a worse overall response rate (ORR: 84.8% vs. 74.9%; OR 1.88 (95% CI: 0.97–3.63), shorter progression‐free survival (PFS) [22.0 vs. 18.2 months; hazard ratio (HR) 0.775; 95%CI: 0.590–1.018; p = 0.066], and overall survival (OS) (45.9 vs. 34.2 months; HR 0.746; 95% CI: 0.551–1.010; p = 0.057). Twenty‐four per cent of patients who had immunoparesis at diagnosis recovered polyclonal immunoglobulins in the follow‐up period. Interestingly, these patients had a better ORR (96.3% vs. 68.2%; OR 12.29 (95% CI: 3.77–40.06), PFS (HR 0.703; 95CI%: 0.526–0.941; p = 0.018) and OS (HR 0.678; 95 CI%: 0.503–0.913; p = 0.011) than patients who did not recover it. In summary, restoring a healthy immune system along with first‐line treatment in patients with MM, not receiving ASCT, is associated with better outcomes.
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