3. Discussion
This is the first case that described the clinical course of ASCT for LCPT with severe kidney injury and the improvement in renal function in detail.
LCPT is a rare subtype of MGRS, and the treatment strategy remains controversial as well as the other types. Previous studies did not support the use of chemotherapy such as alkylating agents because of its ineffectiveness in improving renal function and adverse effects such as secondary malignancy [5]. However, as new drugs for multiple myeloma have become available, 11 case reports and 4 case series have shown the efficacy of chemotherapy, particularly bortezomib-based regimens and ASCT to improve renal and tubular function [12-22] (summarized in Tables 2 and 3). Although these studies comprised a small case series, and the definition of the renal outcome was variable, all reports showed that chemotherapy improved renal function or delayed the progression to end-stage kidney disease, compared with that in the non-chemotherapy group (Table 2). In addition, they reported an improvement in renal tubular function, characterized by the resolution of proteinuria or urinary glucose and elevation of serum phosphate and uric acid levels (Table 2). Although we cannot precisely assess the efficacy of different treatments owing to the small size and heterogeneity of the series, a combination of chemotherapy and ASCT tends to achieve a better renal or proximal tubular function than chemotherapy alone [1,2]. These data suggest that renal and tubular functional improvements can be achieved by reducing the secretion of free light chains by abnormal plasma cells. Although emerging evidence suggests that organ response rate may be improved by negative minimal residual disease in AL amyloidosis, the most common type of MGRS [23], no data are available on whether the complete eradication of abnormal plasma cells is beneficial for the kidneys or delays the progression to multiple myeloma in patients with LCPT.
Recently, daratumumab, an anti-CD38 monoclonal antibody, has been commonly administered for multiple myeloma and AL amyloidosis. Since most of the case reports are published before the approval of daratumumab, the administration of daratumumab for LCPT is limited to only 2 cases, complicated with AL amyloidosis or crystal‑storing histiocytosis respectively. [9,11] Both are efficacious and CD38 monoclonal antibody seems to be a promising therapeutic alternative for LCPT.
It is noteworthy that the renal function improved in our case despite severe initial kidney injury, compared to the extent of renal injury in the previous case reports (Table 3). Although most previous reports include eGFR above 30 mL/min/1.73m2 or creatinine below 2.0 mg/dL, renal injury progressed to eGFR 15.4 mL/min/1.73m2 (creatinine 3.31 mg/dL) at the initiation of treatment in our case. We found only two cases of LCPT with severe kidney injury, one of which showed no improvement of renal function [22], and the other showed remarkable improvement as well as in our case [19]. These data imply that we should aggressively consider the diagnosis by renal biopsy and chemotherapy for LCPT even with severe kidney impairment.
Our study limitation is the uncertainty of whether the addition of ASCT leads to better clinical outcomes. Although the role of ASCT is not established in LCPT, we decided to perform ASCT considering that the patient responded well to chemotherapy with rapid improvement in renal function.
In conclusion, a combination of bortezomib-based chemotherapy and ASCT could effectively treat LCPT and successfully improve the renal function in this patient. Therefore, hematologists should be familiar with LCPT as a differential diagnosis for renal impairment with monoclonal gammopathy of undetermined significance and multiple myeloma and should consider chemotherapy even with severe renal injury. However, data on the best treatment strategy and long-term prognosis are still lacking. Larger prospective studies are needed to support our results and determine the optimal treatment strategy for LCPT.