Outcomes of Modified Mayo Stage IIIa and IIIb Cardiac Light-Chain Amyloidosis: Real-World Experience in Clinical Characteristics and Treatment-67 Patients Multicenter Analysis.

Light-chain amyloidosis (AL) is a rare multisystem disorder characterized by the deposition of misfolded amyloid fibrils derived from monoclonal immunoglobulin light chains in various organs. One of the most common organs involved in AL is the heart, with 50-70% of patients clinically symptomatic at diagnosis. We conducted a multi-center, retrospective analysis of 67 patients diagnosed between July 2012 and August 2022 with the European 2012 modification of Mayo 2004 stage III cardiac AL. The most important factors identified in the univariate Cox analysis contributing to a longer OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1, New York Heart Association functional classification (NYHA FC) ≤ 2, the use of autologous stem cell transplantation (ASCT) after induction treatment, achieving a hematological response (≥very good partial response) and cardiac (≥partial response) response after first-line treatment. The most important prognostic factors with the most significant impact on OS improvement in patients with modified Mayo stage III cardiac AL identified by multivariate Cox analysis are ECOG PS ≤ 1, NYHA FC ≤ 2, and achieving hematological response ≥ VGPR and cardiac response ≥ PR after first-line treatment.

Hematogenous extramedullary relapse in multiple myeloma - a multicenter retrospective study in 127 patients.

The current study assesses the characteristics and outcomes of multiple myeloma (MM) patients, treated with novel agents for hematogenous extramedullary (HEMM) relapse. Consecutive patients diagnosed with HEMM between 2010-2018 were included. Patients' characteristics at diagnosis and at HEMM presentation, response to treatment, survival and factors predicting survival were recorded and analyzed. A group of 127 patients, all diagnosed with HEMM by imaging (87.3%) and/or biopsy (79%), were included. Of those, 44% were initially diagnosed with ISS3, 57% presented with plasmacytomas, and 30% had high-risk cytogenetics. Median time to HEMM was 32 months. In multivariate analysis, ISS3 and bone plasmacytoma predicted shorter time to HEMM (P = .005 and P = .008, respectively). Upfront autograft was associated with longer time to HEMM (P = .002). At HEMM, 32% of patients had no BM plasmacytosis, 20% had non-secretory disease and 43% had light-chain disease. Multiple HEMM sites were reported in 52% of patients, mostly involving soft tissue, skin (29%), and pleura/lung (25%). First treatment for HEMM included proteasome inhibitors (50%), immunomodulatory drugs (IMiDs) (39%), monoclonal antibodies (10%), and chemotherapy (53%). Overall response rate (ORR) was 57%. IMiDs were associated with higher ORR (HR 2.2, 95% CI 1.02-4.7, P = .04). Median survival from HEMM was 6 months (CI 95% 4.8-7.2). Failure to achieve ≥VGPR was the only significant factor for worse OS in multivariate analyses (HR = 9.87, CI 95% 2.35 - 39, P = .001). In conclusion, HEMM occurs within 3 years of initial myeloma diagnosis and is associated with dismal outcome. The IMiDs might provide a higher response rate, and achievement of ≥VGPR predicts longer survival.

Multiple myeloma in patients up to 30 years of age: a multicenter retrospective study of 52 cases.

A small proportion of patients with multiple myeloma (MM) are diagnosed at a very young age. The clinicopathological characteristics and prognosis of these patients are not well known. This analysis included 52 patients diagnosed with MM at the age of ≤30 years (range: 8-30 years). 68% of patients had International Scoring System (ISS) 1 MM; 22% presented with the light chain-only disease, and 48% with elevated serum lactate dehydrogenase (LDH). 85% of patients were treated with novel agents, and 62% received front-line autologous stem cell transplantation (ASCT). Overall response rate (ORR) to front-line treatment and ASCT were 71% and 90%, respectively. The group was followed-up for the median period of 86 months. The median overall survival (OS) was 166 months (95% CI: 53-222), with 5-year OS rate of 77% (95% CI: 61.0-87.9). This findings suggest that the prognosis in young MM patients may be as good if not better than in the general population of MM patients.

Case-adjusted bortezomib-based strategy in routine therapy of relapsed/refractory multiple myeloma shown to be highly effective--a report by Polish Myeloma Study Group.

The observational study was aimed at evaluating response, survival and toxicity of bortezomib-based, case-adjusted regimens in real-life therapy of 708 relapsed/refractory MM patients. Bortezomib was combined with anthracyclines, steroids, thalidomide, alkylators or given in monotherapy. The ORR was 67.9% for refractory and 69.9% for relapsed MM. The median PFS was 14 months and OS 57 months. Patients responding to the therapy had the probability of a 4-year OS at 67.0%. No toxicity was noted in 33.1% of patients. Severe events (grade 3/4) were reported in 35.9% of patients: neurotoxicity (16.7%), neutropenia (9.2%), thrombocytopenia (8.5%), and infections (6.5%). Bortezomib-based, case-adjusted regimens are in real-life practice effective in salvage therapy offering reliable survival with acceptable toxicity for relapsed/refractory MM patients.

Diversity of clinical manifestations and response to corticosteroids for idiopathic hypereosinophilic syndrome: retrospective study in 33 patients.

Idiopathic hypereosinophilic syndrome (IHES) is characterized by blood hypereosinophilia with no underlying cause and eosinophilia-associated organ dysfunction. Thirty-three patients, 20 female (61%) and 13 male (29%), with a median age of 56 years at diagnosis (range 16-77 years) were included in the study. The median blood eosinophilia at diagnosis was 7.6 × 10(9)/L and the median percentage of eosinophils in the bone marrow was 39.5%. The most common clinical manifestations were splenomegaly and cardiac involvement. Corticosteroids (CS) as monotherapy were initiated in all study patients. The median starting dose of prednisone was 30 mg daily (range 5-85 mg), and the maintenance dose varied from 5 mg twice weekly to 60 mg daily. Overall, 21 patients (64%) responded to CS within a week. Seven patients (21%) were resistant or intolerant to CS. Five patients (15%) achieved a 50% reduction of blood eosinophilia. In conclusion, CS were found to be highly effective in IHES with manageable side effects.

The JAK2V617F tyrosine kinase mutation has no impact on overall survival and the risk of leukemic transformation in myelofibrosis.

The prevalence of JAK2V617F tyrosine kinase mutation differs between various variants of myelofibrosis with the higher detection rate for patients with post-polycythemia vera myelofibrosis (post-PV MF; 91%) if compared to primary myelofibrosis (PMF; 45%) and post-essential thrombocythemia myelofibrosis (post-ET MF; 39%). The impact of V617F point mutation and its allele burden on overall survival (OS) and the risk of leukemic transformation (LT) has been the subject of several studies, but the results were ambiguous. Our study included 77 patients with the following variants: 42 patients with PMF (55%), 16 with post-ET MF (21%) and 19 with post-PV MF (24%). Median age at diagnosis for the entire cohort was 61 years (range 19-81), with 53% of female. A total of 42 patients were JAK2V617F positive, giving an overall frequency of 55%; the median allele burden was 22% (range 2-96%). The JAK2V617F point mutation was detected in 21 patients with PMF (50%), 14 with post-PV MF (88%) and 7 with post-ET MF (37%). Lower JAK2V617F allele burden was more frequently detected in PMF patients, whereas higher allele burden was predominantly seen in post-PV/ET MF group. There was no significant difference between V617F-positive and V617F-negative patients in terms of studied parameters in PMF as well as in post-PV/ET MF subgroup. No significant difference was also demonstrated when the above-mentioned subpopulations were analyzed according to JAK2V617F allele burden, except higher leukocyte count in post-PV/ET MF patients with higher allele burden (14.3×10(9)/L vs. 6.2×10(9)/L; p=.03). Median follow-ups for V617F-positive and V617F-negative patients were 16.6 months (range 3.6-206.4) and 36.4 months (range 2.5-142.1), respectively. The presence of JAK2V617F mutation did not affect OS and the risk of LT development.