Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia.

BACKGROUND: A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS: In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS: Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS: The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).

Extracorporeal photopheresis for GVHD prophylaxis after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation: a prospective multicenter phase 2 study.

We performed a prospective multicenter phase 2 study to evaluate the safety and efficacy of prophylactic Extracorporeal Photopheresis (ECP) in adult patients with hematological malignancies early after RIC allo-HSCT on day 21 twice per week during the first two weeks and then once per week for the next four weeks for a total of eight ECP courses. A total of 20 patients were included; 10 were males, median age was 60 years. All patients engrafted, 17 (85%) received the total eight ECP courses. There were no adverse effects related to ECP. Seven patients developed acute graft-versus-host disease (GVHD), with 15% grade ≥ II cumulative incidence at day 100. The cumulative incidence of chronic GVHD at 2 years was 22%. The 2 years probability of overall survival (OS) and progression-free survival (PFS) were 84 and 74%, respectively. This study shows encouraging results with low acute and chronic GVHD incidence and no interference with graft-versus-leukemia (GVL) effect.

Impact of chimaerism analysis and kinetics on allogeneic haematopoietic stem cell transplantation outcome after conventional and reduced-intensity conditioning regimens.

This retrospective study aimed to analyse the impact on overall survival (OS) and event-free survival (EFS) of chimaerism status and kinetics following allogeneic conventional and reduced-intensity conditioning haematopoietic stem cell transplantation, and to compare this with the impact of other well-known factors. We investigated the chimaerism status of 187 patients [84 females, 103 males; median age 39.5 years (range, 17-62 years)]. After transplantation, 121 patients (65%) presented full donor chimaerism (FDC) and 63 (34%) mixed chimaerism (MC). For MC, we divided the population into patients who presented regressive mixed chimaerism (RMC) (21 patients: 11%), stable mixed chimaerism (SMC) (20 patients: 11%) and progressive mixed chimaerism (PMC) (22 patients: 12%). At last follow-up, 71 patients were alive and 116 had died (48% from disease progression and 52% from transplant-related causes). With a mean follow-up of 39.4 and 34.8 months, the 5-year probabilities of OS and EFS for the total group were, respectively, 55% and 43%: 69.5% and 61% for FDC, 35.4% and 25% for RMC, 42.6% and 28.6% for SMC, and 21% and 10.4% for PMC (P < 0.0001 and P < 0.0001). Multivariate analysis only showed a significant impact of chimaerism status on OS, as well as acute and chronic graft-versus-host disease on EFS, with a trend for conditioning regimen.