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.