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.
Highlights
Multiple myeloma (MM) is a plasma cell neoplasm characterized by the presence of monoclonal immunoglobulin (Ig) in serum and/or urine and clinical symptoms related to hypercalcemia, renal insufficiency, anemia, and bone lesion (CRAB features), and myeloma-defining events [1,2].MM is a clinically and cytogenetically heterogeneous disease, and survival outcome varies considerably depending on the risk status such as disease stage and cytogenetic abnormalities, and treatment of each patient [3].Cancers 2020, 12, 12; doi:10.3390/cancers12010012 www.mdpi.com/journal/cancersUntil now, treatment strategy for MM has been evolving rapidly by the introduction of several new classes of agents such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies [4]
Some patients have achieved minimal residual disease (MRD) negativity that is considered as a major prognostic factor for progression-free survival (PFS) and overall survival (OS) [6,7]
We have demonstrated that patients with polyclonal Ig recovery 1 year after autologous stem cell transplantation (ASCT) had a significantly better PFS and OS than those without Ig recovery
Summary
Multiple myeloma (MM) is a plasma cell neoplasm characterized by the presence of monoclonal immunoglobulin (Ig) in serum and/or urine and clinical symptoms related to hypercalcemia, renal insufficiency, anemia, and bone lesion (CRAB features), and myeloma-defining events [1,2].MM is a clinically and cytogenetically heterogeneous disease, and survival outcome varies considerably depending on the risk status such as disease stage and cytogenetic abnormalities, and treatment of each patient [3].Cancers 2020, 12, 12; doi:10.3390/cancers12010012 www.mdpi.com/journal/cancersUntil now, treatment strategy for MM has been evolving rapidly by the introduction of several new classes of agents such as proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), and monoclonal antibodies (elotuzumab and daratumumab) [4]. Randomized clinical trials have shown the efficacy of continuous therapy in non-transplanted patients and maintenance therapy after ASCT in transplanted patients for both PFS and OS [8,9] Adverse events such as second primary malignancies and infections have been reported with lenalidomide maintenance [9,10], and gastrointestinal disorders and rash with ixazomib maintenance [11]. It has not been established whether patients with deep response such as MRD negative have real benefit from continuous and maintenance therapy because of possible adverse events and cost problems in routine clinical practice [12,13]
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