Light-Chain Deposition Disease Treatment & Management

Updated: Jan 15, 2017
  • Author: Swapna Boppana, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Treatment

Medical Care

Treatment of light-chain deposition disease (LCDD) is indicated for patients who present with systemic involvement, renal dysfunction, and associated presence of multiple myeloma. The goal of treatment in these patients is to suppress the production of light chains and damage to other organs. Appropriate medical management must be provided for organ dysfunction as needed, such as the use of angiotensin-converting enzyme (ACE) inhibitors or dialysis.

Unlike in multiple myeloma, the plasma cell burden is quite low (<5%) and the genetic abnormalities associated with adverse prognosis in multiple myeloma are absent. In patients with LCDD associated with multiple myeloma, the prognosis is quite poor and they should be treated per multiple myeloma guidelines. [35] In these patients, there is no evidence to support maintenance therapy except for an anecdotal report in 1 patient who received thalidomide maintenance following chemotherapy. [36] LCDD is a rare disease, hence there are no established guidelines and management remains controversial. [37]

Treatment options include the following [53] :

  • Autologous stem cell transplantation (ASCT)
  • Bortezomib
  • Immunomodulatory drugs
  • Renal transplantation

Autologous stem cell transplantation

Stem cell transplantation can produce durable responses in patients with LCDD. [37, 38, 39] Stem cells are mobilized using granulocyte colony-stimulating factor (G-CSF), and high-dose chemotherapy with melphalan is given. The dose of melphalan is adjusted to the renal function to decrease morbidity.

A long-term analysis of 6 patients with LCDD who underwent ASCT demonstrated that this is an effective therapy for patients with renal dysfunction due to LCDD. [37] Proteinuria was reduced by 92%, and the glomerular filtration rate improved by 95% in these patients. The authors also suggest if kidney dysfunction persists after ASCT, a hematological response may permit successful kidney transplantation with improved graft viability and decreased risk of recurrence. Another study of patients with LCDD treated with high-dose melphalan followed by ASCT also demonstrated that patients with renal dysfunction have improvement in renal function following ASCT. [40] Of the 5 evaluable patients with hematological response, one had complete response and four with partial response.

The use of high dose chemotherapy followed by ASCT is associated with toxicities such as mucositis, sepsis, bacteremia, and diarrhea. In general, LCDD patients are younger; thus, ASCT should be considered in these patients. However, associated comorbidities, presence of cardiac involvement, concomitant presence of multiple myeloma, and number of organs affected may predict for a worse outcome. Therefore, age and comorbidities should be considered prior to ASCT. Multiorgan failure following ASCT has been reported in patients with extrarenal disease. [37]

Bortezomib

In light-chain deposition disease (LCDD), monoclonal light chains interact with the receptors in mesangial cells and activate many pathways including the nuclear factor (NF)kB pathway. This results in increased cytokine production leading to cell proliferation and activation of genes responsible for collagen and tenascin production. These changes lead to changes in the mesangial matrix ,causing glomerulosclerosis. [9, 12] Bortezomib inhibits the NFkB pathway, decreases cytokine production, and decreases collagen production. [41, 42] The downstream cascade is interrupted by bortezomib preventing rapid progression of glomerulosclerosis and proteinuria and improving the renal function. [42, 43]

Bortezomib has been used in small series of patients with LCDD, including as induction therapy. [39, 44, 45] In one series, 3 patients were treated with bortezomib as induction therapy. This led to rapid hematologic response after a mean of 2 cycles based on decrease in serum free light-chain levels. [44] Another series reported the use of bortezomib with dexamethasone as induction therapy prior to autologous stem cell transplantation (ASCT) in 4 patients, which lead to rapid response with 50% of patients with complete hematologic response. [45] A Canadian group reported the use of bortezomib and dexamethasone as induction therapy in 2 patients prior to ASCT, and both achieved partial response after 3 cycles and organ response 6 months after ASCT. [38]

The Canadian group also reported the only randomized study of 6 patients with LCDD. Patients were randomized to either dexamethasone alone or bortezomib with dexamethasone prior to high-dose chemotherapy with melphalan followed by ASCT. After completion of induction therapy 4 of 6 patients achieved partial response based on the decrease in serum free light-chain ratio and 2 of 6 achieved stable disease and both were in dexamethasone alone group.

At day 100, the post-ASCT overall response rate was 100%; 4 patients achieved complete hematological response, 1 exhibited near-complete response, and 1 attained partial response. All patients derived clinical benefit, including those who achieved less than complete response. At 6 months post-ASCT, all 6 patients showed organ response manifested mainly by decreased proteinuria of greater than 50%. Patients receiving bortezomib and dexamethasone induction showed a median time of kidney response of 3 months versus 6 months for the group receiving only dexamethasone. All 6 patients are alive after a median follow up of 2 years and have remained dialysis free. [46]

Based on the limited available data, induction with bortezomib helps improve renal function. This may possibly lead to more high-dose chemotherapy followed by ASCT, enabling for a better outcome. With bortezomib-based therapy, hematologic responses are rapid and are normally accompanied by rapid and significant reduction of proteinuria and improvement of renal function. The measurement of serum free light chains was useful in the follow-up of patients with LCDD, and the reduction of involved light chains was associated with significant improvement of proteinuria. High dose chemotherapy followed with ASCT is a safe and well-tolerated treatment for LCDD, showing a good overall response rate.

Immunomodulatory agents

Thalidomide is an immunomodulatory drug that has been extensively studied in amyloid light-chain (AL)–amyloidosis and multiple myeloma. The use in LCDD has been limited. A report in one young patient in whom conventional chemotherapy failed demonstrated that thalidomide with dexamethasone was able to provide a complete hematological response after 8 months. The patient had a sustained hematological response with improvement in renal function that lasted 31 months. [47]

Another case was reported in a patient with liver involvement who was given lenalidomide with melphalan and prednisone. However, lenalidomide was discontinued as the patient unfortunately developed intrahepatic ischemic cholangitis. [48]  

In another case, melphalan and prednisolone (MP) therapy was started upon diagnosis and continued for 10 years with serial evaluations of renal histology revealing the resolution of nodular lesions, and the glomeruli became nearly normal. [55] The immunomodulatory agents are promising but their role needs to be further explored in prospective studies.

Renal transplantation

A few patients with LCDD with ESRD have undergone renal transplantation. [49]  Long-term benefits are seen, but allograft survival is significantly reduced in this patient population. [54] LCDD patients who have detectable light chains in urine or serum have worse outcomes, with early recurrences despite pretransplantation treatment. [50] Thus, transplantation should be reserved for select patients with a relatively slow course in whom light-chain production can be controlled by directed therapy.

Despite all careful consideration, recurrences develop and sometimes can be confused with acute rejection. A recent study with bortezomib in a single patient suggests that it can successfully reverse early recurrence of LCDD in the allograft. [51] Rituximab could also be considered for delaying early LCDD recurrence in patients in whom treatment of the underlying bone marrow disorder failed or is contraindicated, but maintenance therapy is apparently necessary to consolidate this response. [52] The possibility of maintenance with either bortezomib, thalidomide, or rituximab needs to be further explored.