Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis

Immunoglobulin light-chain (AL) amyloidosis is a rare, incurable plasma cell disorder. Its therapy has benefited immensely from the expanding drug armamentarium available for multiple myeloma. Pomalidomide in combination with weekly dexamethasone (Pom/dex) is active among patients with relapsed myeloma. In the present study, we explored the Pom/dex combination in patients with previously treated AL. Patients were eligible for this prospective phase 2 trial if they had had at least one prior regimen and if they had reasonably preserved organ function. Patients were treated with oral Pom/dex. Thirty-three patients were enrolled. The median age was 66 years. Median time from diagnosis to on-study was 37 months. Eighty-two percent had cardiac involvement. The confirmed hematologic response rate was 48%, with a median time to response of 1.9 months. Organ improvement was documented in 5 patients. The median overall and progression-free survival rates were 28 and 14 months, respectively; the 1-year overall and progression-free survival rates were 76% and 59%, respectively. There was a discordance between the hematologic response and the N-terminal probrain natriuretic peptide response. The most common grade 3-5 adverse events, regardless of attribution, were neutropenia and fatigue. We conclude that pomalidomide appears to be a valuable drug covering an unmet clinical need in patients with previously treated AL. The trial is registered at www.clinicaltrials.gov as NCT00558896. (Blood. 2012;119(23): 5397-5404

Asymptomatic Amyloidosis at the Time of Diagnostic Bone Marrow Biopsy in Newly Diagnosed Patients with Multiple Myeloma and Smoldering Multiple Myeloma.

Background.: The rate of asymptomatic amyloidosis (asym-amyloidosis) detected in patients with newly diagnosed multiple myeloma (MM) or smoldering multiple myeloma (SMM) is unknown. This topic is significant because unrecognized AL may be associated with increased mortality may change the patient's management. The objective of the present investigation was to evaluate the number and clinical significance of asym-amyloidosis in MM and SM patients at the time of the diagnostic bone marrow (BM) biopsy for MM. Materials and Methods.: The study population was selected from the Mayo Clinic Dysproteinemia database and consisted of consecutive patients with an established diagnosis of MM or SMM without recognition of symptomatic AL. Bone marrow biopsies at diagnosis of MM or SMM were retrospectively stained with Congo Red and reviewed by a single pathologist. A patient was considered to have asym-amyloid if Congo Red staining with apple green birefringence was found. Results.: Biopsies from 144 (M 84, F 59) patients were evaluated: 77 had a diagnosis of MM and 67 of SMM. The median age was 59 (range 26-84) years. No differences were found regarding hemoglobin, platelets, prothrombin time, serum and urine proteins, serum albumin, alkaline phosphate, creatinine and \u3b22-microglobulin among MM and SMM patients. At a median follow-up 76 months (range 0-216), 32% patients were alive, 65% dead and 2.7% lost to follow-up. Immunoglobulin isotypes were as follows: 96/144 (67%) had IgG 23/144 (16%) IgA, 12/144 (8%) had light chain only, 1/77 (1%) had IgD, none had IgM and 12/144 (8%) had biclonal or indeterminate; 84/144 (58%) were restricted. The presence of amyloid was found in only 2 cases (1%, 95% CI \u2013 0.6 to 3.2), 1 in MM and 1 in SMM group. Neither of these patients had or developed signs or symptoms suggestive of organ involvement by amyloid. Among the 142 other patients without amyloid deposition in their index bone marrow, 1 (0.7%, 95% CI -0.6 to 2.0) developed symptomatic AL after 119 months of follow-up. Characteristics of these three patients are shown in table 1. Conclusions.: We found only 2 cases (1%) of amyloidosis in the 144 cases of MM or SMM. Our estimates are lower than the rates which have been reported by others, perhaps because of our high level of suspicion for amyloid at our Amyloidosis Center. These data do not support the need for searching for asym-amyloidosis in patients with newly diagnosed MM or SMM as long as they have no clinical features of A

A detailed evaluation of the current renal response criteria in al amyloidosis: is it time for a revision?

Organ response correlates with overall survival in patients with immunoglobulin light chain amyloidosis and is the goal of treatment. This study evaluates the current renal response criteria and their ability to predict overall survival. Patients with immunoglobulin light chain amyloidosis who underwent autologous stem cell transplantation between 1995 and 2010 were recruited. Eligibility criteria included >1 g/dL of proteinuria, dialysis independence at baseline and within the first year of autologous stem cell transplantation, and a minimum follow-up of 1 year. Responses were assessed by the best values after autologous stem cell transplantation. The difference between involved and uninvolved serum free light chain levels was used to determine hematologic response. Increases in serum creatinine were calculated from the highest creatinine after autologous stem cell transplantation. Inclusion and exclusion criteria were met by 141 patients. These patients had a median follow-up of 52 months. Superior overall survival was observed in patients with a >75% reduction in proteinuria and those who had a >95% reduction had additional benefits. The overall survival of patients with >50% to <= 75% proteinuria was similar to that of patients with <= 50% reduction. A rise in serum creatinine >25% was not associated with a poorer outcome in patients with a >75% reduction in proteinuria. Deeper hematologic responses were associated with higher rates of proteinuria reduction. These results suggest that further evaluation of the current renal response criteria is needed. In particular, discrimination of the renal response into complete and partial categories and modification of the serum creatinine requirement seem justified

Isolated amyloidosis presenting with lumbosacral radiculoplexopathy: Description of two cases and pathogenic review

In this study, we present two cases of infiltrative, localized amyloidosis involving lumbosacral root and plexus, e.g., isolated amyloidomas. Rare and poorly understood amyloidomas may occur in both neurologic and non-neurologic tissues. The described cases emphasize potential for localized peripheral amyloidomas: (1) potential for associated λ light chain lymphoplasmacytic lymphoma association; (2) e isolated amyloidosis without evidence for systemic plasma cell dyscrasia; (3) features suggestive of potential pathogenesis; and (4) discussion of treatment options including immunotherapy and resection. The limited literature and experience among other cases is described. © 2006 Peripheral Nerve Society