Abstract
Background: Monoclonal Immunoglobulin deposition disease (MIDD) is characterized by non-amyloidogenic linear amorphous deposition of monoclonal immunoglobulin within the basement membrane of glomeruli, tubules, and blood vessels in the renal parenchyma. The majority of patients with this disorder have an underlying monoclonal plasma cell population in the bone marrow, resulting in the production of misfolded light chain immunoglobulin, which then gets deposited in the kidneys. The current treatment recommendations include the use of plasma-cell directed therapies to deplete the production of this monoclonal protein. Recent development of CD38 monoclonal antibodies has revolutionized the therapy of multiple myeloma, but these drugs have not been well evaluated for the therapy of MIDD.
Methods: We conducted a multi-center retrospective analysis of patients diagnosed with MIDD at three academic medical centers. All patients had an organ biopsy consistent with pathological diagnosis of MIDD. Patient demographics, organ involvement, renal function, and proteinuria were recorded. Data on the hematologic characteristics were reviewed, including monoclonal protein, involved serum free light chain concentration and ratio, baseline bone marrow analysis, and cytogenetic analysis. In addition, we collected data on therapies and long-term outcomes, including hematologic responses, renal responses, rates of dialysis and organ transplantation, and mortality. The primary outcome of interest was renal survival, defined as the time from initiation of clone-directed therapy to initiation of renal replacement therapy (RRT) or renal transplantation.
Results: We identified a total of 42 patients with biopsy-proven diagnosis of MIDD. Median age of patients was 63 years (Range 45-72), 53% males. The majority of patients presented with renal dysfunction and/or proteinuria, and the diagnosis was confirmed in all patients with a renal biopsy. Kappa-type monoclonal protein deposition was seen in 83% of patients. Monoclonal plasma cells were present in all patients in bone marrow biopsy, with a median involvement of 7% (range 2-65%). On FISH studies, t(11;14) was identified in 38% of patients. Monoclonal protein was detected on SPEP in 54% of patients, and the median light chain ratio was 23 (range 2-287). Median serum creatinine and eGFR at diagnosis were 2.1 mg/dl (range 0.8-11.8) and 27 mL/min (range 5-80), respectively. Two patients were started on dialysis at the time of diagnosis. All patients were treated with plasma cell-directed therapy, with the regimen cyborD (bortezomib, cyclophosphamide, dexamethasone) being the most commonly used regimen. Daratumumab-based therapy was used in ten patients, with Dara-CyborD being the most commonly used regimen in these patients. Seven patients (all in the Non-Dara arm) underwent a consolidative autologous stem cell transplant. Thus, we divided the patients into two groups, namely Dara (N=10) and Non-Dara (N=32) to study the effect of Daratumumab use. The median eGFR at diagnosis was similar in the two groups (30 vs 27, p = 0.31). Rates of overall hematologic response were comparable in two groups (90 vs 75%, P=0.31). Similarly, the rates of CR/VGPR were also similar in the two groups (70% vs 40%, P=0.10). The Renal response defined by improvement in eGFR was higher in the Dara group as compared to the Non-Dara group (77% vs 40%, P= 0.04), and the median degree of improvement in eGFR was similar at about 30% in both groups. With a median follow-up of 27 months, the rate of progression to ESRD was significantly lower in the Dara group as compared to Non-Dara group (10% vs 40% P=0.04). Conclusion: Use of Daratumumab based therapy is associated with deep hematologic responses as well as improvement in renal responses in patients with MIDD. In addition, Daratumumab use significantly decreased the risk of progression to ESRD in this patient population. Further prospective studies should be done to evaluate use of Daratumumab in MIDD.
