Lacy, Martha Q.

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.

Catheter Ablation for Atrial Arrhythmias in Patients With CABackgroundCardiac amyloidosis (CA) is associated with increased atrial arrhythmias risk. The efficacy/safety of catheter‐based ablation therapy in patients with CA has not been adequately assessed.Methods and ResultsAll diagnosed CA patients who underwent atrial arrhythmia ablation therapy from 1995 to 2015 were reviewed. Arrhythmia recurrence, NYHA symptoms, and mortality were recorded. A total of 26 patients with CA and atrial arrhythmias were included; there were 7 light‐chain (AL), 17 wild‐type transthyretin (ATTRwt), and 2 mutated transthyretin (ATTRm) amyloidosis patients in total. Of which 13 underwent atrial arrhythmia ablation (CA‐A) and 13 underwent AV nodal ablation (CA‐AVN). In the CA‐A group, there were: 3 with atrial fibrillation (AF); 6 with atrial flutter (AFL); 2 with AF/AFL; and 2 with atrial tachycardia (AT). One‐year and 3‐year recurrence‐free survival were 75% and 60%, respectively. NYHA symptom improvement 6 months postablation was observed in both CA‐A and CA‐AVN groups: 7/10 (70%) and 4/8 (50%), respectively. Eleven patients with CA died (8 in CA‐AVN group vs. 3 in CA‐A group).ConclusionsCatheter‐based ablation for patients with CA appears to provide important symptomatic relief. However, mortality from the underlying disease remains a significant issue for the amyloid light‐chain subtype.

There is no consensus on whether patients with immunoglobulin light chain amyloidosis (AL) should receive induction therapy prior to an autologous stem cell transplant (ASCT). This study investigated the relationships between baseline bone marrow plasmacytosis (BMPC), cardiac staging, and pre‐transplant induction in AL patients. All patients who received ASCT for AL within 12 months of diagnosis were included. Patient characteristics and outcomes were abstracted. Univariate and multivariate modeling was performed. Among 415 AL patients, 35% had induction prior to ASCT. Post‐ASCT hematologic CR plus VGPR rates were significantly higher in those with baseline BMPC ≤ 10% compared to BMPC >10% (58% versus 40%, P = 0.0013). Significant risk factors for lack of attainment of CR included attenuated dose melphalan conditioning, baseline BMPC > 10%, no induction, and male gender. The 5‐year OS for the entire group was 65%. On multivariate analysis, risk factors for inferior OS included no induction therapy, advanced AL amyloid staging, BMPC > 10%, attenuated conditioning melphalan dose, and male gender. Patients with Mayo 2012 stage I–II patients with BMPC ≤ 10%, who comprised 56% of the ASCT population fared exceedingly well regardless of whether or not they received induction therapy with a 5‐year OS of 81 to 83%. Induction therapy pre‐ASCT may improve outcomes among AL patients due to a rapid reduction of toxic light chains or alternatively by elimination of less fit patients by “testing” their ability to tolerate chemotherapy. Prospective studies will be required to sort out these and other questions. Am. J. Hematol. 91:984–988, 2016. © 2016 Wiley Periodicals, Inc.

BACKGROUNDAutologous stem cell transplantation (SCT) is a common management strategy for select patients with immunoglobulin light‐chain amyloidosis, but no trials have documented improved overall survival.METHODSEighty‐nine patients with biopsy‐proven immunoglobulin light‐chain amyloidosis were allowed to select treatment with melphalan plus dexamethasone (n = 34) or SCT (n = 55); all patients were transplant eligible. Treatment preference resulted in imbalanced study arms. Patients who selected SCT were younger, more frequently had an Eastern Cooperative Oncology Group performance status score less than 2, had lower‐stage amyloidosis, and had a lower incidence of cardiac amyloidosis.RESULTSPatients receiving melphalan plus dexamethasone had a 3‐year progression‐free survival rate of 29.1% and an overall survival rate of 58.8%. Patients undergoing SCT had a 3‐year progression‐free survival rate of 51.7% and an overall survival rate of 83.6%. An attempt to match patients between the 2 arms in terms of risk produced 24 matched triplet sets (2 SCT patients for each melphalan‐dexamethasone patient); there was no difference in hematologic response, but there was better survival after autologous SCT. A propensity score–matched analysis of the cohorts (melphalan plus dexamethasone vs SCT) showed an overall mortality hazard ratio of 2.56 (P < .01).CONCLUSIONSAlthough the study had limitations, similar hematologic responses and improved survival were observed after SCT versus melphalan plus dexamethasone. Cancer 2016;122:2197–205. © 2016 American Cancer Society.

Over the past decade, a number of changes have occurred in the diagnostic evaluation, management, and long‐term follow‐up of patients with POEMS syndrome at our institution. This study included 291 patients with POEMS syndrome diagnosed at the Mayo Clinic between 1974 and 2014. Patients diagnosed after 2003 had more features of the syndrome identified at diagnosis and were more likely to receive an autologous transplant (49% versus 8%, P < 0.0001) and to have achieved a hematologic complete response (CR) to treatment (41% vs 25%, P < 0.0001). With 2273 person‐years of follow‐up, 10‐year overall survival (OS) was 62% (95% C.I., 56%, 67%). On multivariate analysis, the three factors associated with superior OS were younger age (RR 0.98 [0.96–1.00]), albumin greater‐than 3.2 g/dL (RR 0.5 [0.32–0.89]) and attainment of complete hematologic response (RR 0.4 [0.2, 0.9]). This study confirms the very good long‐term outcomes of patients with POEMS syndrome and identifies two new prognostic risk factors: albumin at diagnosis and attainment of complete hematologic response. Am. J. Hematol. 91:585–589, 2016. © 2016 Wiley Periodicals, Inc.

We report the long‐term follow‐up results of a phase II trial of IL‐1 receptor antagonist and low‐dose dexamethasone for early stage multiple myeloma (MM). Patients were eligible if they had smoldering multiple myeloma (SMM) or indolent multiple myeloma (IMM) without the need for immediate therapy. Forty seven patients were enrolled and subsequently treated with IL‐1Ra; in 25/47 low‐dose dexamethasone (20 mg weekly) was added. The primary endpoint was progression‐free survival (PFS). In the clinical trial, three patients achieved a minor response (MR) to IL‐1Ra alone; five patients a partial response (PR) and four patients an MR after addition of dexamethasone. Seven patients showed a decrease in the plasma cell labeling index (PCLI) which paralleled a decrease in the high sensitivity C‐reactive protein (hs‐CRP). The median PFS for the 47 patients was 1116 days (37.2 months). The median PFS for patients without (n = 22) and with (n = 25) a decrease in their baseline hs‐CRP was 326 days (11 months) vs. 3139 days (104 months) respectively (P <0.0001). The median overall survival (OS) for the 47 patients was 3482 days (9.5 years). The median OS for patients without and with a decrease in their baseline hs‐CRP was 2885 days (7.9 years) vs. median not reached, respectively (P = 0.001). In SMM/IMM patients at risk for progression to active myeloma, reduction in the hs‐CRP indicates successful targeting of the IL‐1/IL‐6 axis resulting in improved PFS and OS.(Clinical Trials.gov Identifier: NCT00635154) Am. J. Hematol. 91:571–574, 2016. © 2016 Wiley Periodicals, Inc.