Revisiting conditioning dose in newly diagnosed light chain amyloidosis undergoing frontline autologous stem cell transplant: impact on response and survival.

Autologous stem cell transplantation (ASCT) is an important treatment modality in light chain (AL) amyloidosis. Use of reduced-dose melphalan conditioning is common, given the associated organ and functional decline. The impact of full-intensity melphalan conditioning (n=314) was compared to reduced-dose conditioning (n=143).

Clinical presentation and outcomes of patients with type 1 monoclonal cryoglobulinemia.

We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n = 43, 42%) and ulcers/gangrene (n = 35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n = 24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients. An underlying lymphoproliferative disorder was identified in 94 (92%) subjects; MGUS-39, myeloma-20, lymphoplasmacytic lymphoma-21 and others-14.

Treatment patterns and outcome following initial relapse or refractory disease in patients with systemic light chain amyloidosis.

We analyzed the outcomes following initial relapse or refractory disease in systemic light chain amyloidosis (AL) and the impact of type of therapy employed.A total of 1327 patients with AL seen at Mayo Clinic within 90 days of diagnosis, between 2006 and 2015, were reviewed. The study included 366 patients experiencing a documented hematological or organ relapse or refractory disease requiring start of second line therapy.

Therapy for Relapsed Multiple Myeloma: Guidelines From the Mayo Stratification for Myeloma and Risk-Adapted Therapy.

Life expectancy in patients with multiple myeloma is increasing because of the availability of an increasing number of novel agents with various mechanisms of action against the disease. However, the disease remains incurable in most patients because of the emergence of resistant clones, leading to repeated relapses of the disease. In 2015, 5 novel agents were approved for therapy for relapsed multiple myeloma.

Overuse of organ biopsies in immunoglobulin light chain amyloidosis (AL): the consequence of failure of early recognition.

Introduction: The diagnosis of amyloidosis requires histological confirmation of Congo-red (CR) deposits. The tissue source is preferably fat aspiration and/or bone marrow (BM) biopsy, but at times organ biopsy is required.

Methods: We studied 612 patients with systemic immunoglobulin light chain amyloidosis to characterise the tissues used to establish the diagnosis.

A phase 2 study of lenalidomide, rituximab, cyclophosphamide, and dexamethasone (LR-CD) for untreated low-grade non-Hodgkin lymphoma requiring therapy.

Patients with indolent non-Hodgkin lymphoma (NHL) have multiple treatment options yet there is no consensus as to the best initial therapy. Lenalidomide, an immunomodulatory agent, has single agent activity in relapsed lymphoma. This trial was conducted to assess feasibility, efficacy, and safety of adding lenalidomide to rituximab, cyclophosphamide, and dexamethasone (LR-CD) in untreated indolent NHL patients requiring therapy.

Clinical utility of the Revised International Staging System in unselected patients with newly diagnosed and relapsed multiple myeloma.

We analyzed the utility of Revised International staging system (RISS) in an unselected cohort of newly diagnosed multiple myeloma (NDMM; cohort 1), and relapsed/refractory multiple myeloma (RRMM; cohort 2) patients. Cohort 1 included 1900 patients seen within 90 days of diagnosis, from 2005 to 2015, while cohort 2 had 887 patients enrolled in 23 clinical trials at Mayo Clinic. The overall survival (OS) and progression-free survival (PFS) was calculated from the time since diagnosis or trial registration.

Hematology patient reported symptom screen to assess quality of life for AL amyloidosis.

Patients 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.

Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death.

In light of major advances in immunoglobulin light chain (AL) amyloidosis, we evaluated the trends in presentation, management, and outcome among 1551 newly diagnosed AL amyloidosis patients seen in our institution from 2000 to 2014. As compared with the 2 intervals 2000-2004 and 2005-2009, patients diagnosed in 2010-2014 were less likely to have >2 involved organs. Utilization of autologous stem cell transplant (ASCT) was similar across all periods, about one-third of patients, but there was an increase in the use of pre-ASCT bortezomib induction and of unattenuated melphalan conditioning in 2010-2014 compared with earlier periods.

Impact of Post-Transplant Response and Minimal Residual Disease on Survival in Myeloma with High-Risk Cytogenetics.

The impact of depth of response and minimal residual disease (MRD) status on survival is not well defined in multiple myeloma (MM) with high-risk (HR) cytogenetics because of the low representation of such patients in clinical trials. We have evaluated the impact of post-transplant stringent complete response (sCR) and MRD status on progression-free survival (PFS) and overall survival (OS) in 185 consecutive MM patients with HR fluorescence in situ hybridization cytogenetics undergoing upfront autologous stem cell transplantation between 2007 and 2015 in our institution. The median age at transplant was 61 years.

Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines 2016.

Importance: Waldenström macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, has witnessed several practice-altering advances in recent years. With availability of a wider array of therapies, the management strategies have become increasingly complex. Our multidisciplinary team appraised studies published or presented up to December 2015 to provide consensus recommendations for a risk-adapted approach to WM, using a grading system.

Risk stratification in myeloma by detection of circulating plasma cells prior to autologous stem cell transplantation in the novel agent era.

The impact of circulating plasma cells (CPCs) prior to autologous stem cell transplantation (ASCT) for multiple myeloma has not been defined in the novel agent era. We evaluated the impact of pre-transplant CPCs, detected by six-color flow cytometry in patients undergoing early ASCT on post-transplant response, progression-free survival (PFS) and overall survival (OS). CPCs were detected in 162 out of 840 (19.

Interphase fluorescence in situ hybridization in untreated AL amyloidosis has an independent prognostic impact by abnormality type and treatment category.

The significance of interphase fluorescence in situ hybridization (iFISH) by regimen type was assessed in 692 immunoglobulin light-chain (AL) amyloidosis patients with iFISH at diagnosis. First-line treatment was categorized as stem cell transplant and three non-transplant regimens. The most common abnormality was t(11;14) (49% of patients) followed by monosomy 13/del(13q) (36%) and trisomies (26%).

IAP antagonists induce anti-tumor immunity in multiple myeloma.

The cellular inhibitors of apoptosis (cIAP) 1 and 2 are amplified in about 3% of cancers and have been identified in multiple malignancies as being potential therapeutic targets as a result of their role in the evasion of apoptosis. Consequently, small-molecule IAP antagonists, such as LCL161, have entered clinical trials for their ability to induce tumor necrosis factor (TNF)-mediated apoptosis of cancer cells. However, cIAP1 and cIAP2 are recurrently homozygously deleted in multiple myeloma (MM), resulting in constitutive activation of the noncanonical nuclear factor (NF)-κB pathway.

Autologous stem cell transplant for multiple myeloma patients 70 years or older.

Autologous stem cell transplant (Auto-SCT) is increasingly used in older patients with multiple myeloma (MM), despite lack of phase 3 trials in this age-defined population. For 207 consecutive MM patients who underwent Auto-SCT and were 70 years or older at transplant (study cohort), data were analyzed and compared with a younger cohort (1764 Auto-SCT patients <70 years old). The proportion of Auto-SCT in the older patients increased from 7.

Early relapse following initial therapy for multiple myeloma predicts poor outcomes in the era of novel agents.

Outcomes for patients with multiple myeloma (MM) have improved in recent years owing to use of novel agents and high-dose therapy followed by autologous stem cell transplant (ASCT). We analyzed the outcomes of 511 consecutive patients treated with novel therapies at our institution between 2006 and 2014 to determine the impact of relapse within 12 months of initiating treatment. A total of 82 patients (16.

Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib.

Proteasome inhibitors have become an integral part of myeloma therapy. Considerable efforts have gone into optimizing this therapeutic approach to obtain maximal proteasome inhibition with least toxicity. Ixazomib is the first oral proteasome inhibitor to enter the clinic and has been studied as a single agent as well as in various combinations.

N-terminal fragment of the type-B natriuretic peptide (NT-proBNP) contributes to a simple new frailty score in patients with newly diagnosed multiple myeloma.

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.

Outcomes of patients with renal monoclonal immunoglobulin deposition disease.

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.

Beta-blockers improve survival outcomes in patients with multiple myeloma: a retrospective evaluation.

A preclinical study demonstrated anti-proliferative and apoptotic effect of propranolol on multiple myeloma (MM) cell. Clinical studies suggested that beta-blocker (BB) might impact the prognosis of breast, prostate, colorectal, ovarian, lung, and skin cancer. This retrospective study evaluated the effect of BB in MM disease-specific survival (DSS) and overall survival (OS).

The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment.

Multiparametric flow cytometry (MFC) in amyloid light-chain (AL) amyloidosis has not been widely adopted and, consequently, there is little information on its clinical relevance. We studied 173 patients with AL amyloidosis who underwent MFC immunophenotyping of bone marrow sample at diagnosis and 82 patients at the end of the first line of treatment (EOT). The number of monotypic plasma cells (PCs) and the polytypic PCs/bone marrow PCs (pPCs/BMPCs) ratio were analyzed.

Systemic Immunoglobulin Light Chain Amyloidosis-Associated Myopathy: Presentation, Diagnostic Pitfalls, and Outcome.

Objective: To characterize the natural history of immunoglobulin light chain amyloidosis-associated myopathy and to provide guidelines for recognition.

Patients And Methods: Fifty-one patients with systemic immunoglobulin light chain amyloidosis and biopsy-confirmed muscle amyloid deposition diagnosed between January 1, 1995, and December 31, 2015, were included in this study.

Results: Common presenting symptoms were muscle weakness in 49 patients (96%), dysphagia in 23 (45%), myalgia in 17 (33%), macroglossia in 17 (33%), jaw claudication in 13 (25%), and hoarseness in 9 (18%).

Myelomatous Involvement of the Central Nervous System.

Introduction: Limited data exist with respect to the outcome and optimal treatment of patients with myelomatous involvement of the central nervous system (CNS).

Materials And Methods: Of 4060 patients with multiple myeloma (MM), evaluated at Mayo Clinic from 1998 to 2014, 29 (0.7%) had identifiable CNS involvement, established by the presence of atypical plasma cells in the cerebrospinal fluid (CSF) and/or identification of intraparenchymal or meningeal involvement on magnetic resonance imaging (MRI).

The impact of induction regimen on transplant outcome in newly diagnosed multiple myeloma in the era of novel agents.

We compared overall survival (OS) of 1017 patients with newly diagnosed multiple myeloma (MM) who were treated with different novel agent-based induction regimens and who underwent early autologous stem cell transplant (ASCT). Subgroups were defined by type of induction therapy: cyclophosphamide-bortezomib-dexamethasone (CyBorD; n=193), bortezomib-dexamethasone (Vd; n=64), lenalidomide-dexamethasone (Rd; n=251), bortezomib-lenalidomide-dexamethasone (VRd; n=126), thalidomide-dexamethasone (Td; n=155) and vincristine-doxorubicin-dexamethasone or dexamethasone alone (VAD/Dex; n=228). The median follow-up of the surviving patients was 66.