Polyclonal Immunoglobulin Recovery after Autologous Stem Cell Transplantation Is an Independent Prognostic Factor for Survival Outcome in Patients with Multiple Myeloma

Abstract

We retrospectively analyzed multiple myeloma (MM) patients who underwent autologous stem cell transplantation (ASCT) without maintenance therapy to assess the impact of recovery of normal immunoglobulin (Ig) on clinical outcomes. The recovery of polyclonal Ig was defined as normalization of all values of serum IgG, IgA, and IgM 1 year after ASCT. Among 50 patients, 26 patients showed polyclonal Ig recovery; 14 patients were in ≥complete response (CR) and 12 remained in non-CR after ASCT. The patients with Ig recovery exhibited a significantly better progression-free survival (PFS, median, 46.8 vs. 26.7 months, p = 0.0071) and overall survival (OS, median, not reached vs. 65.3 months, p < 0.00001) compared with those without Ig recovery. The survival benefits of Ig recovery were similarly observed in ≥CR patients (median OS, not reached vs. 80.5 months, p = 0.061) and non-CR patients (median OS, not reached vs. 53.2 months, p = 0.00016). Multivariate analysis revealed that non-CR and not all Ig recovery were independent prognostic factors for PFS (HR, 4.284, 95%CI (1.868–9.826), p = 0.00059; and HR, 2.804, 95%CI (1.334–5.896), p = 0.0065, respectively) and also for OS (HR, 8.245, 95%CI (1.528–44.47), p = 0.014; and HR, 36.55, 95%CI (3.942–338.8), p = 0.0015, respectively). Therefore, in addition to the depth of response, the recovery of polyclonal Ig after ASCT is a useful indicator especially for long-term outcome and might be considered to prevent overtreatment with maintenance therapy in transplanted patients with MM.

Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial

“…However, this impact was seen in the landmark analysis one year after ASCT and not in the landmark analyses conducted at earlier time points [ 16 ]. These results are in line with two other studies and can be explained by completed B-cell reconstitution one year after ASCT [ 38 , 41 , 42 ]. It has to be noted that, currently, there are only a few retrospective studies on the prognostic effect of immune reconstitution after ASCT and that further studies are needed to clarify the optimal time point of assessment.…”

Multiple myeloma treatment – should be continued or not?

“…Mateos et al in Spain have focused on the recovery of polyclonal immunoglobulins as an indicator available in routine clinical practice, and have demonstrated that approximately half of the patients achieved immunoglobulin recovery 1 year after autologous stem cell transplantation even though about half were under maintenance therapy either with interferon‐alpha, bortezomib, or IMiDs 2 . As expected, the progression‐free survival and overall survival of these patients were significantly better than those of patients without recovery, and this phenomenon in transplanted patients has also been confirmed by several researchers including our group 3–5 . In this issue of the journal, Davila et al the same research group in Spain, present similar results in non‐transplanted patients, that is, approximately one‐quarter of patients showed immunoglobulin recovery within 1 month or up to 36 months (median 6 months) after the start of treatment 1 .…”

“…2 As expected, the progression-free survival and overall survival of these patients were significantly better than those of patients without recovery, and this phenomenon in transplanted patients has also been confirmed by several researchers including our group. [3][4][5] In this issue of the journal, Davila et al the same research group in Spain, present similar results in non-transplanted patients, that is, approximately one-quarter of patients showed immunoglobulin recovery within 1 month or up to 36 months (median 6 months) after the start of treatment. 1 Treatment regimens were 46.6% for conventional chemotherapy, 45.9% for PI-based (only 2.7% with daratumumab), 4.4% for IMiD-based, and 3.0% for PIs and IMiDs combined, and notably, 81% were under fixed-duration therapy.…”

Restoring Humoral Immunity after Autologous Stem Cell Transplantation in Multiple Myeloma and Response to Post-transplantation Vaccination

“…Interestingly, the cohort with immunoglobulin recovery had a statistically significant longer progression-free survival than the group with persistent immunoparesis (median PFS 60.4 vs. 27.9 months, respectively), and improved overall survival (11.3 vs. 7.3 years, respectively). Furthermore, additional studies supporting that recovery of immunoglobulins one year after ASCT is an independent predictor of longer PFS and OS [10,11]. The authors postulated that immunoparesis might be connected to impaired immunosurveillance as well as increased infectious complications, hence the importance of post-transplantation vaccinations.…”