Treatment of Light Chain (AL) Amyloidosis and Light Chain Deposition Disease (LCDD) with the Combination of Bortezomib and Dexamethasone.
Authors: Kastritis Efstathios , Anagnostopoulos Athanasios , Roussou Maria , Toumanidis Savvas , Pamboukas Constantinos , Tassidou Anna , Xilouri Irini , Delimpassi Sossana , Psimenou Erasmia , Mellou Sofia , Terpos Evangelos , Nanas John , Dimopoulos Meletios Athanasios 
Published: April 2020

Abstract
Background: Primary (AL) amyloidosis and light chain deposition disease (LCDD) are clonal plasma cells disorders characterized by deposition of either amyloid fibrils (in AL) or amorphous nodular non-congophilic deposits (in LCDD) derived from abnormal light chains, that cause failure of affected organs. Treatment of AL is based on steroids and standard dose or high dose melphalan with ASCT. Data on treatment of LCDD are limited. Bortezomib, a proteasome inhibitor, has significant activity in myeloma, which is enhanced by the addition of dexamethasone (BD) and can be given in myeloma patients with renal impairment. We evaluated this combination in patients with AL and LCDD.
Methods: We treated consecutive patients with AL or LCDD with the combination of Bortezomib (1.3 mg/m2 days 1, 4, 8 and 11) and Dexamethasone (40 mg days 1–4), every 21 days, for up to 6 cycles. Dose modifications were made based on toxicity. Organ involvement and hematologic and organ response were assessed following standard criteria (Gertz et al, Am J Hematol 2005).
Results: Since September 2005, 21 consecutive AL and 2 LCDD patients started treatment with BD. Eight patients (38%) had at least one prior therapy and 13 (62%) had ≥2 organs involved; kidneys and heart were affected in most patients. The majority had impaired performance status, high BNP values and 7 (33%) patients had creatinine&gt;2 mg/dl. Among the 21 AL patients, 2 are early for evaluation, 4 had non-measurable disease and 15 patients are evaluable: 13 (87%) responded (CR+PR) and 7 (47%) achieved hematologic CR. All 5 patients refractory to high dose DEXA had a hematologic response and 3 had a CR. Two of 3 AL patients with abnormal FLC ratio but involved FLC&lt;100 mg/L achieved normal FLC ratio. Both patients with LCDD responded- the patient who was refractory to VAD had a CR. Median time to hematologic response was 0.93 months; all responses occurred within 2 courses while all patients in hematologic CR maintain CR for a median of 10.5 months (range 4.6–21). So far, 6 (28%) AL patients had organ responses (3 renal and 3 cardiac) while 7 (44%) patients had a sustained &gt;50% reduction in BNP. Median time to organ response in AL patients was 4 months (range 2–8). In both LCDD patients albuminuria was reduced by more than 50%. Median follow-up for all patients and for living patients is 9.5 months (range 1–23) and 12 months (range 4–23) respectively. In an intention to treat basis 8 (38%) patients have progressed, including 3 AL patients (14%) who died while on treatment (with two of them at hematologic PR at the time of their death- one died before she was assessable for response). Five AL patients had either hematologic or organ progression at a median of 6.8 months after treatment initiation. Peripheral neuropathy, fatigue, peripheral edema, constipation and exacerbation of postural hypotension were managed with appropriate dose adjustment; however 10 (47%) patients were not able to receive the planned 6 courses.
Conclusions: The combination of BD is feasible for patients with AL amyloidosis and LCDD. Most patients achieve rapid hematologic response and toxicity can be managed with close follow-up and appropriate dose adjustment. This treatment may be a valid option for patients with severe heart or kidney impairment who are not candidates for other therapies.