Added text to state that the absence of plasma cells on flow cytometry of the bone marrow suggests a low risk of recurrence after radiation therapy of the isolated bone plasmacytoma (cited Paiva et al. as reference 35).
Revised text to state that magnetic resonance imaging (MRI) scans of the total spine and pelvis may identify other bony lesions.
Added text to state that accurate diagnosis of amyloidosis requires histologic evidence of amyloid deposits and characterization of the amyloidogenic protein using immunoelectron microscopy. In one series of 745 consecutive patients, 20% of patients with non-amyloid light chain amyloidosis had an innocent monoclonal gammopathy, indicating the significant risk of misdiagnosis (cited Fernández de Larrea et al. as reference 45).
Revised text of the criteria from the International Myeloma Working Group, which identifies patients with active myeloma who require therapy, to include bone lesions on skeletal radiography, whole-body MRI or spine and pelvis MRI, or positron emission tomography-computed tomography (PET-CT) scans (cited Dimopoulos et al. as reference 6). An additional revision stated more than one focal lesion of at least 5 mm on skeletal bone survey, or if negative, total-body MRI, or MRI of the spine and pelvis, or PET-CT scan.
Added text to state that treatment depends on assessing the extent of systemic damage from the amyloidosis and the underlying plasma cell dyscrasia. Also added that a rising and elevated level of N-terminal pro brain natriuretic peptide may predict impending cardiac failure in the setting of cardiac amyloidosis, and early treatment should be considered for these patients (cited Merlini et al. as reference 1).
Revised list of parameters suggested for use as an initial approach to evaluate the patient (cited Rajkumar et al. as reference 1, and Dimopoulos et al. [J Clin Oncol 2015] as reference 2).
Added text to state that in fit patients, triple-drug regimens are considered standard treatment in the absence of a clinical trial and added the most commonly used triplets.
Added text to question whether as newer agents, such as carfilzomib and pomalidomide, move upfront into triplets, and with the introduction of the anti-CD38 monoclonal antibody daratumumab and the monoclonal antibody targeting SLAMF7 elotuzumab, will the stringent complete remissions equal or surpass autologous stem cell transplantation with less long-term toxicities? Added that additional unresolved questions about multiple myeloma therapies include: How to incorporate the newer agents such as daratumumab and elotuzumab upfront creating four or five drug regimens? Can a more personalized targeted approach be found to create a smaller cocktail? What about the financial toxicity of these advances?
Added text to include two additional therapeutic agents that are available for induction therapy, either alone or in combinations: daratumumab (monoclonal antibody targeting CD38) and elotuzumab (monoclonal antibody targeting SLAMF7).
Added text to state that a meta-analysis of 3,254 individual patients from seven randomized trials showed that lenalidomide was associated with an increased risk of hematologic second primary malignancies (3.1% in patients who received lenalidomide vs. 1.4% in those who did not); this risk was confined to the combination of lenalidomide and melphalan but was not higher for lenalidomide with either cyclophosphamide or dexamethasone (cited Palumbo et al. as reference 29).
Added text to state that a meta-analysis of 1,685 patients from six of the randomized trials confirmed that thalidomide added to melphalan plus prednisone (MP) improves the median overall survival (OS) from 32.7 months to 39.3 months (cited Fayers et al. as reference 48 and level of evidence 1iiA).
Added text to state that a prospective, randomized trial of 260 newly diagnosed patients aged 65 years and older compared bortezomib plus melphalan plus prednisone (VMP) with bortezomib plus thalidomide plus prednisone; with a median follow-up of 72 months, the median OS favored the VMP arm, 63 months versus 43 months (cited Mateos et al. as reference 58 and level of evidence 1iiA).
Added text to state that in a prospective, randomized trial of 929 patients with relapsed or refractory multiple myeloma, carfilzomib and dexamethasone were compared with bortezomib and dexamethasone (cited Dimopoulos et al. [Lancet Oncology 2016] as reference 65 and level of evidence 1iiDiii); with a median follow-up of about 1 year, the median progression-free survival (PFS) was 18.7 months for the carfilzomib combination compared with 9.4 months for the bortezomib combination.
Revised text to state that in two phase II trials of newly diagnosed patients aged 65 years and older, carfilzomib combined with cyclophosphamide and dexamethasone in 58 patients or with MP in 68 patients achieved at least a partial response in 95% of the patients and a near complete response (nCR) in 90% of the patients (cited Moreau et al. as reference 68 and level of evidence 3iiiDiv).
Revised text to state that in two trials of 53 and 45 patients with newly diagnosed disease, carfilzomib combined with lenalidomide and dexamethasone achieved an nCR or stringent complete response in 62% of the patients in both trials and an 18- to 24-month PFS of 92% also in both trials (cited Korde et al. as reference 70 and level of evidence 3iiiDiv).
Added text about the new combination regimen, bortezomib, lenalidomide, and dexamethasone (VRd) versus lenalidomide and dexamethasone (Rd) and stated that in a prospective, randomized trial in 474 newly diagnosed patients with myeloma, VRd was compared with Rd (cited Durie as reference 90 and level of evidence 1iiA). Also added that with a median follow-up of 55 months, the VRd group had superior PFS and OS.
Added option of carfilzomib plus pomalidomide plus dexamethasone to list of combination regimens (cited Shah et al. as reference 97).
Added text to state that a cellular therapy for refractory myeloma has been introduced that consists of autologous T-cells transduced with an anti-CD19 chimeric antigen receptor after myeloablative chemotherapy and autologous stem cell transplantation, with anecdotal responses. Other molecular targets and expanded clinical approaches are being investigated (cited Garfall et al. as reference 3 and level of evidence 3iiiDiv).
ver historia personal en: www.cerasale.com.ar [dado de baja por la Cancillería Argentina por temas políticos, propio de la censura que rige en nuestro medio]//
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