Advances in the management of thalassemia
Andreas E. Kulozik, Franco Locatelli, Evangelia Yannaki, John B. Porter, et al.
Conclusion: Early data from Northstar-3 suggest that improvements in DP manufacturing are resulting in improved DP VCN, HbAT87Q production, and total Hb levels after treatment with LentiGlobin gene therapy for TDT. The 2 patients with ≥6 months follow-up have stopped RBC transfusions and total Hb levels are >10 g/dL. Longer follow-up and data from additional patients are needed to demonstrate whether the manufacturing refinements ultimately translate into improved clinical outcomes for patients with TDT and β0/β0 genotypes.
Mark C. Walters, Janet L. Kwiatkowski, John E. J. Rasko, Suradej Hongen, et al.
Conclusion: With up to 4 years of follow-up, we observed durable transfusion independence in 8/10 and 3/8 patients with non-β0/β0 genotypes and β0/β0 genotypes, respectively, and a safety profile that is consistent with myeloablative conditioning. Two ongoing Phase 3 studies, Northstar-2 and Northstar-3, are evaluating refined manufacturing of LentiGlobin with the goal to improve patient outcomes.
Vania Manolova, Naja Nyffenegger, Anna Flace, Patrick Altermatt, et al.
Conclusion: Iron restriction by pharmacologically targeting the Fpn-hepcidin axis with the first in-class oral Fpn inhibitor VIT-2763 provides a novel therapeutic opportunity in β-thalassemia.
Maria-Domenica Cappellini, Martin Schwickart, Olivier Hermine, Antonio Piga, et al.
Conclusion: Luspatercept treatment was associated with increased HbF in patients with RBC TD β-thalassemia. This luspatercept treatment effect on increasing HbF levels was observed in both responders and non-responders. Luspatercept-mediated increases in HbF were observed early and maintained throughout the treatment period.
Antonis Kattamis, Mariagrazia Felisi, Giorgio Reggiardo, Amal El-Beshlawy, et al.
Conclusion: This FP7-sponsored trial on chelation therapy in pediatric patients with TDH is the largest in this age group and the only one comparing the two oral chelating agents. The results of the study show that 1) oral iron chelation treatment is effective even in very young ages, 2) treatment with DFP was not inferior to DFX in patients who received 12 months treatment, 3) NI was not shown in the ITT analysis partially due to a different rate of withdrawal not necessarily mandated by the protocol, 4) the overall safety profile of both DFP and DFX was acceptable. The results of the DEEP-2 trial provide evidence to support the use of DFP in pediatric patients.