Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival.

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.

Correction to: Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival.

The original version of this article contained a mistake. The name of Eirini Katroditou should have been Eirini Katodritou. The original article has been corrected.

Real-world complication burden and disease management paradigms in transfusion-related ß-thalassaemia in Greece: Results from ULYSSES, an epidemiological, multicentre, retrospective cross-sectional study.

Patients with transfusion-dependent beta (ß)-thalassaemia experience a broad range of complications. ULYSSES, an epidemiological, multicentre, retrospective cross-sectional study, aimed to assess the prevalence and severity of treatment and disease complications, capture disease management and identify predictors of complications in patients with transfusion-dependent ß-thalassaemia, treated in routine settings in Greece. Eligible patients were adults diagnosed with ß-thalassaemia ≥12 months before enrolment and having received ≥6 red blood cell (RBC) units (excluding elective surgery) with no transfusion-free period ≥35 days in the 24 weeks before enrolment. Primary data were collected at a single visit and through chart review. Between Oct 21, 2019, and Jun 15, 2020, 201 eligible patients [median (interquartile range, IQR) age 45.7 (40.2-50.5) years; 75.6% > 40 years old; 64.2% female] were enrolled, a mean (standard deviation) of 42.9 (7.8) years after diagnosis. Median (IQR) age at diagnosis and RBC transfusion initiation were 0.8 (0.4-2.8) and 1.3 (1.0-5.0) years, respectively. From diagnosis to enrolment, patients had developed a median of six (range: 1-55) complications; 19.6% were grade ≥3. The most represented complications were endocrine/metabolic/nutrition disorders (91.5%), surgical/medical procedures (67.7%) and blood/lymphatic system disorders (64.7%). Real-world data generated by ULYSSES underscore the substantial complication burden of transfusion-dependent ß-thalassaemia patients, routinely managed in Greece.

Luspatercept: A New Tool for the Treatment of Anemia Related to ß-Thalassemia, Myelodysplastic Syndromes and Primary Myelofibrosis.

Anemia is a common feature of both benign and malignant hematologic diseases. Beta-thalassemia (ß-thalassemia) syndromes are a group of hereditary disorders characterized by ineffective erythropoiesis, due to a genetic deficiency in the synthesis of the beta chains of hemoglobin, often accompanied by severe anemia and the need for red blood cell (RBC) transfusions. Myelodysplastic syndromes (MDS) are characterized by cytopenia(s) and ineffective hematopoiesis, despite a hypercellular bone marrow. Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm characterized by reactive fibrosis of the bone marrow, accompanied by extramedullary hematopoiesis. Luspatercept, previously known as ACE-536, is a fusion protein that combines a modified activin receptor IIB (ActRIIB), a member of the transforming growth factor-ß (TGF-ß) superfamily, with the Fc domain of human immunoglobulin G (IgG1). It has shown efficacy in the treatment of anemia due to beta ß-thalassemia, MDS and PMF and recently gained approval by the Federal Drug Agency (FDA) and the European Medicines Agency (EMA) for transfusion-dependent (TD) patients with ß-thalassemia and very low to intermediate-risk patients with MDS with ringed sideroblasts who have failed to respond to, or are ineligible for, an erythropoiesis-stimulating agent. In this review, we describe the key pathways involved in normal hematopoiesis and the possible mechanism of action of luspatercept, present its development and data from the most recent clinical trials in ß-thalassemia, MDS and PMF, and discuss its potential use in the treatment of these hematological disorders.