Citations

PURPOSE: Primary systemic amyloidosis is an immunoglobulin deposition disorder in which insoluble light chains cause organ dysfunction and death. The established conventional therapy is treatment with melphalan and prednisone. We investigated whether treatment with multiple alkylating agents improved the response rate or survival time, compared with melphalan and prednisone therapy. PATIENTS AND METHODS: We treated 101 patients with biopsy-proven primary amyloidosis. The patients were randomly assigned to receive melphalan and prednisone (52 patients) or vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (49 patients). Patients were stratified according to the presence of cardiac involvement, time from diagnosis to randomization, serum beta2-microglobulin level, and whether peripheral neuropathy was the major manifestation of the disease. RESULTS: The median duration of survival after randomization was 29 months, with no differences in survival time between the two groups. There were 29 patients who fulfilled the response criteria: 15 in the vincristine, carmustine, melphalan, cyclophosphamide, and prednisone arm and 14 in the melphalan and prednisone arm. CONCLUSION: Therapy with multiple alkylating agents did not result in a higher response rate or longer survival time, compared with standard melphalan and prednisone treatment in patients with primary systemic amyloidosis.

AbstractPatients with light chain amyloidosis (AL) often have delayed diagnosis and present with significant symptomatology; this may result in decreased quality of life (QOL). We prospectively employ a “Hematology Patient Reported Symptom Screen” (HPRSS), which is three questions about fatigue, pain, and QOL, scored 0–10. The aim of this study is to better understand QOL and determine if HPRSS parameters predict for clinical outcomes. From 2009 to 2014, 302 newly diagnosed AL patients were included. Baseline median scores [interquartile range] for fatigue, pain, and QOL were 6 [3,7], 2 [0,5], 5 [3,8], respectively. Median overall survival was 53 months, with 102 (34%) deaths in the first year. There were significant differences in baseline HPRSS between those that lived longer than one year and early death patients in the domains of fatigue (5 [IQR 3, 7] vs. 7 [IQR 5, 8], P < 0.0001) and QOL (6 [IQR 4, 8] vs. 5 [IQR 3, 7], P = 0.006). On univariate analysis fatigue, QOL, physician‐reported performance status, autologous stem cell transplant (ASCT), and Mayo stage were prognostic for survival. On multivariate analysis Mayo stage, ASCT, and baseline fatigue remained independently prognostic. When analyses were restricted to the 125 patients with HPRSS measurements at 12 months, we found that over time QOL scores improved significantly 6 [IQR 3.5, 8] → 7 [IQR 5, 8] (P = 0.01). Asking AL patients to rate their fatigue and QOL has predictive value. Baseline patient reported fatigue is an independent prognostic factor for survival. Survival at one year was associated with significant improvement in QOL.

The clinical nature of laryngeal amyloidosis has not been well established, and the natural history of the disease remains a controversial matter. To address these issues, we reviewed the clinicopathologic and immunohistochemical features of 22 cases (11 men and 11 women; mean age, 56 years) of laryngeal amyloidosis. Hoarseness was the most common symptom, and the most frequent site affected was the false vocal cords. Six patients had concomitant tracheal amyloidosis. Paraffin blocks were available for immunostaining in 20 cases. Nineteen cases were positive for amyloid P component. λ‐Light chains were detected in 12 cases and κ‐light chains in 5; three cases did not show definite light‐chain staining. Ten patients underwent repeated operations for persistent or recurrent respiratory tract disease. One patient died of progressive tracheobronchial amyloidosis, but systemic amyloidosis did not develop in any of the patients. Laryngeal amyloidosis is a form of localized amyloidosis characterized by monoclonal light‐chain deposition. Recurrent respiratory tract disease is not uncommon, but the usual clinical course is relatively benign.

Key Points Significant improvement in outcome is a reality for newly diagnosed AL amyloidosis in the past decade. Six-month mortality among transplant ineligible patients has declined since 2005.

Key PointsThe monotypic and polytypic PC compartments assessed by MFC are prognostic in AL amyloidosis. MFC may play a role in the definition of hematologic response to treatment.

Abstract BACKGROUND Electrophoretic separation of serum and urine proteins has played a central role in diagnosing and monitoring plasma cell disorders. Despite limitations in resolution and analytical sensitivity, plus the necessity for adjunct methods, protein gel electrophoresis and immunofixation electrophoresis (IFE) remain front-line tests. METHODS We developed a MALDI mass spectrometry–based assay that was simple to perform, automatable, analytically sensitive, and applicable to analyzing the wide variety of monoclonal proteins (M-proteins) encountered clinically. This assay, called MASS-FIX, used the unique molecular mass signatures of the different Ig isotypes in combination with nanobody immunoenrichment to generate information-rich mass spectra from which M-proteins could be identified, isotyped, and quantified. The performance of MASS-FIX was compared to current gel-based electrophoresis assays. RESULTS MASS-FIX detected all M-proteins that were detectable by urine or serum protein electrophoresis. In serial dilution studies, MASS-FIX was more analytically sensitive than IFE. For patient samples, MASS-FIX provided the same primary isotype information for 98% of serum M-proteins (n = 152) and 95% of urine M-proteins (n = 55). MASS-FIX accurately quantified M-protein to &lt;1 g/dL, with reduced bias as compared to protein electrophoresis. Intraassay and interassay CVs were &lt;20% across all samples having M-protein concentrations &gt;0.045 g/dL, with the ability to detect M-proteins &lt;0.01 g/dL. In addition, MASS-FIX could simultaneously measure κ:λ light chain ratios for IgG, IgA, and IgM. Retrospective serial monitoring of patients with myeloma posttreatment demonstrated that MASS-FIX provided equivalent quantitative information to either protein electrophoresis or the Hevylite™ assay. CONCLUSIONS MASS-FIX can advance how plasma cell disorders are screened, diagnosed, and monitored.

Multiple myeloma (MM) patient frailty has been delineated primarily by age and ECOG performance score (PS) and recently by the IMWG frailty score based on functional status [Activity of Daily Living (ADL) and Instrumental‐ADL scores], comorbidities [Charlson‐comorbidity‐index (CCI)] and age. It was hypothesized that N‐terminal natriuretic peptide type B (NT‐proBNP) might be both a more convenient measure of frailty and a predictor of overall survival (OS). Three‐hundred and fifty‐one consecutive symptomatic MM patients who were seen at Mayo Clinic within 30 days of diagnosis and who had blood stored were eligible. Data from the first visit was abstracted and used to calculate an ADL, CCI, and measure the NT‐proBNP level. The best cutoff of NT‐proBNP predicting OS was 300 ng/L. Variables predictive for OS were ECOG‐PS, age, CCI, ADL, ISS, revised‐ISS, and NT‐proBNP. On multivariate analysis age ≥70, PS ≥2, and NT‐proBNP ≥300 were independent predictors of survival. Patients were assigned a score of 1 for each of these variables, creating stages I–IV with scores of 0–3 points, respectively. The median OS from diagnosis was not reached, 58, 28, and 18 months (P < 0.0001), respectively. This frailty risk schema was independent of initial therapy and the revised‐ISS. NT‐proBNP is a useful predictor of survival independent of age and PS. It is a widely available biomarker that could be added to the panel of laboratory tests of newly diagnosed MM patients and serve as a simple and objective tool of determining frailty in clinical practice. Am. J. Hematol. 91:1129–1134, 2016. © 2016 Wiley Periodicals, Inc.

Recent reports suggest that deep hematologic responses to chemotherapy are associated with improved renal outcomes in monoclonal immunoglobulin deposition disease (MIDD). Here we describe the long term outcomes and identify prognostic factors after first line treatment of the largest reported series of patients with MIDD. Between March 1992 and December 2014, 88 patients with MIDD were seen at Mayo Clinic, MN. Renal responses were defined using criteria used for light chain amyloidosis (AL) or those used by the IMWG. Sixty‐one (69%) patients had a GFR < 30 mL/min/1.73 m2 and 16 (18%) were on renal replacement therapy at diagnosis. The interval between albuminuria or elevation in creatinine and MIDD diagnosis was 12 months suggesting a delay in diagnosis. Thirty‐seven patients (42%) had at least a hematologic CR/VGPR. Fifty‐three (60%) received an autologous stem cell transplant (ASCT) or proteasome inhibitor (PI)‐based treatments. Patients receiving ASCT or PI‐based therapies were more likely to achieve at least a hematologic CR/VGPR compared to those receiving other therapies: 66% vs 2%, p < 0.0001. Patients that achieved a hematologic CR were more likely to achieve a renal response (53% vs 24%, p = 0.001). Five year overall and renal survival for the entire cohort was 67% and 57%, respectively. In multivariate analyses, a baseline GFR < 20 mL/min/1.73 m2 and a renal response (using AL or IMWG criteria) were independently predictive of progression to dialysis. This study confirms that deep hematologic responses, best achieved with ASCT or PI‐based therapies, are a prerequisite to achieving renal responses. Am. J. Hematol. 91:1123–1128, 2016. © 2016 Wiley Periodicals, Inc.