Citations

AbstractConsiderable progress has been made in the treatment of multiple myeloma in the past decade with median survival for the disease improving significantly. This has come through a combination of better understanding of the disease biology and coordinated research into new treatment approaches including better supportive care. However, patients eventually become refractory to available treatments and succumb to the disease, highlighting the need to develop new treatment approaches. The genetic heterogeneity in the disease and clonal evolution under treatment pressure underlie the development of resistance, underscoring the need to develop more effective therapies that can eradicate the disease at initial treatment as well as the need for new classes of drugs with varying mechanisms of action. To this end, there has been intense focus on exploring novel approaches to therapy including small-molecule inhibitors targeting specific abnormalities, immune therapies including monoclonal antibodies and adaptive T-cell therapy, as well as epigenetic approaches. Although many of these drugs are in the early stages of clinical development, the early data appear to be very promising. Many of these drugs can be safely and effectively combined with the current treatment classes such as proteasome inhibitors and immunomodulatory drugs, further enhancing the treatment options for myeloma.

Abstract We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic immunoglobulin light chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. The NT-proBNP was elevated (>300 pg/mL) in all 159 patients (sensitivity, 100%; median NT-proBNP, 4917 pg/mL; range, 355-69 541). The left ventricular ejection fraction, interventricular septal thickness, and strain rate were abnormal in 89/168 (53%), 102/64 (61%) and 92/95 (97%), respectively. Among cohort 2 (n = 342), 259 (76%) had an elevated NT-proBNP, of whom 237 (92%) had an abnormality detected on TTE. Of 83 patients with normal NT-proBNP <300 pg/mL, 27 (33%) had an abnormality on TTE (all with borderline strain rate −18% to −15%). Only 5/27 patients were considered to have possible early cardiac involvement and none had any other diagnostic or classical features of amyloidosis on TTE. The combination of NT-proBNP and comprehensive echocardiographic evaluation can diagnose cardiac amyloidosis negating the need for endomyocardial biopsy. A negative NT-proBNP rules out clinically meaningful cardiac involvement and may obviate the routine use of TTE in patients with a low clinical suspicion of cardiac amyloidosis.