Outcomes of therapeutic plasma exchange for the treatment of patients with multiple myeloma cast nephropathy.

Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell-directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi-institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy.

Management of Relapsed-Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice.

Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases.

External validation of the SAVED score for venous thromboembolism risk stratification in patients with multiple myeloma receiving immunomodulatory drugs.

Selective patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiD) are at high risk for venous thromboembolism (VTE). The SAVED score is a VTE risk prediction model recently incorporated into the National Comprehensive Cancer Network (NCCN) guidelines. Using retrospective data from 501 MM patients with new IMiD initiation between 2010 and 2019, we performed the first independent external validation of this model.

Abnormal metaphase cytogenetics predicts venous thromboembolism in myeloma: derivation and validation of the PRISM score.

Although venous thromboembolism (VTE) is an important treatment and disease-related complication in myeloma, a validated risk prediction model including disease-specific variables such as cytogenetics or tumor burden is lacking. The aim of this study was to develop a new risk prediction model for VTE in the context of modern antimyeloma therapy. All consecutive patients diagnosed at the Cleveland Clinic between 2008 and 2018 and with available data on baseline candidate risk factors constituted the derivation cohort.

Pomalidomide, dexamethasone, and daratumumab immediately after lenalidomide-based treatment in patients with multiple myeloma: updated efficacy, safety, and health-related quality of life results from the phase 2 MM-014 trial.

Patients with relapsed/refractory multiple myeloma (RRMM) need proven subsequent therapies after early-line lenalidomide treatment failure. The phase 2 MM-014 trial (NCT01946477) investigated pomalidomide, dexamethasone, and daratumumab after 1 to 2 prior treatment lines (62.5%, 1 prior line) in patients with RRMM and prior lenalidomide (75.

Validation of the IMPEDE VTE score for prediction of venous thromboembolism in multiple myeloma: a retrospective cohort study.

The IMPEDE VTE score has recently emerged as a novel risk prediction tool for venous thromboembolism (VTE) in multiple myeloma (MM). We retrospectively reviewed 839 patients with newly diagnosed MM between 2010 and 2015 at Cleveland Clinic and included 575 patients in final analysis to validate this score. The c-statistic of the IMPEDE VTE score to predict VTE within 6 months of treatment start was 0·68 (95% CI: 0·61-0·75).

DNA methylation inhibition in myeloma: Experience from a phase 1b study of low-dose continuous azacitidine in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma.

The DNA methyltransferase inhibitor azacytidine (aza) may reactivate pathways associated with plasma cell differentiation, cell cycle control, apoptosis, and immune recognition and thereby restore sensitivity to lenalidomide (len) and dexamethasone (dex) in relapsed and/or refractory multiple myeloma (RRMM). We aimed to develop an aza regimen that reaches epigenetically active levels 8 times in 28 days with less bone marrow toxicity than the myeloid malignancy standard of 7 consecutive doses to enable safe combination with len. Aza was escalated from 30 mg/m once a week up to a predefined maximum of 50 mg/m twice a week in combination with GFR-adjusted len (≥ 60 mL/min: 25 mg, 3059 mL/min: 10 mg) day 1 to 21 every 28 days and dex 40 mg once a week followed by a limited expansion study to a total N of 23 at the highest tolerated dose.

Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma after lenalidomide treatment.

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles).

Primary amyloidosis of the breast excised using an oncoplastic reduction approach.

We present a case of surgical removal of primary amyloidosis of the breast utilizing an oncoplastic reduction pattern technique. Primary amyloidosis of the breast is a very rare benign disease characterized by accumulation of insoluble amyloid protein. Biopsy is required for definitive diagnosis, and surgical removal of the mass with clear margins is the main treatment for primary amyloidosis.

Mitral and tricuspid stenosis caused by light chain cardiac amyloid deposition.

Cardiac amyloidosis results in an infiltrative restrictive cardiomyopathy, with a number of characteristic features: biventricular hypertrophy, abnormal myocardial global longitudinal strain with relative apical sparing, biatrial dilation, and small pericardial effusion along with conduction abnormalities. Amyloid deposits leading to hemodynamically significant valvular heart disease are very rare. We describe a rare case of concomitant moderately severe tricuspid and mitral valve stenosis because of ongoing amyloid deposition in a patient with progressive multiple myeloma and fat pad biopsy-proven light chain amyloidosis.

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma.

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma (MM) is lacking in the current literature. We evaluated 258 patients with relapsed MM, diagnosed from 2008 to 2015, to investigate the prognostic impact of deep immunoparesis on post-relapse survival. On qualitative immunoparesis assessment, no, partial and full immunoparesis was present in 9%, 30% and 61% of patients, respectively.

Pomalidomide plus low-dose dexamethasone in relapsed refractory multiple myeloma after lenalidomide treatment failure.

Patients with relapsed/refractory multiple myeloma (RRMM) for whom the benefits of lenalidomide have been exhausted in early treatment lines need effective therapies. In cohort A of the phase 2 MM-014 trial, we examined the safety and efficacy of pomalidomide plus low-dose dexamethasone immediately after lenalidomide-based treatment failure in patients with RRMM and two prior lines of therapy. Pomalidomide 4 mg was given on days 1 to 21 of 28-day cycles.

Treatment of relapsed multiple myeloma: Evidence-based recommendations.

The practice of choosing the next best therapy for patients with relapsed and/or refractory multiple myeloma (RRMM) is becoming increasingly complex. There is no clear consensus regarding the best treatment sequence for RRMM. With the approval of novel proteasome inhibitors (ixazomib and carfilzomib), immunomodulatory agents (pomalidomide), monoclonal antibodies (daratumumab and elotuzumab), and other targeted therapies, multiple combination regimens utilizing these agents are being studied with the goal of enhancing disease control, prolonging progression-free survival, and improving overall survival.

Patient-reported outcomes in systemic AL amyloidosis with functional assessment of cancer therapy-general (FACT-G) and patient-reported outcomes measurement information system-global health (PROMIS-GH) in a real-world population.

We performed an observational study on health-related quality of life (HRQoL) in patients with AL amyloidosis diagnosed between 2012 and 2017 at our institution. A total of 81 patients were included, with a median age of 64 years. The mean FACT-G (Functional Assessment of Cancer Therapy-General) total score at baseline (≤2 months from diagnosis) was 74 (±15), compared to a normative score of 80 (±18) in the general U.

Future of Personalized Therapy Targeting Aberrant Signaling Pathways in Multiple Myeloma.

Multiple myeloma (MM) is a genetically complex disease. Identification of mutations and aberrant signaling pathways that contribute to the progression of MM and drug resistance has potential to lead to specific targets and personalized treatment. Aberrant signal pathways include RAS pathway activation due to RAS or BRAF mutations (targeted by vemurafenib alone or combined with cobimetinib), BCL-2 overexpression in t(11:14) (targeted by venetoclax), JAK2 pathway activation (targeted by ruxolitinib), NF-κB pathway activation (treated with DANFIN combined with bortezomib), MDM2 overexpression, and PI3K/mTOR pathway activation (targeted by BEZ235).