EHA Press Briefing, Friday, June 14, 2019
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| Results from the Randomized, Placebo-Controlled, Phase 3 Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization (HOPE) Trial of Voxelotor in Adults and Adolescents with Sickle Cell Disease (abstract S147)
Presenter: Dr Jo Howard – United Kingdom
Conclusion: Voxelotor treatment demonstrated a dose-dependent increase in Hb, with the majority of patients on voxelotor 1500 mg achieving a >1.0-g/dL improvement in Hb from baseline to week 24. In addition, there was a dose-dependent decrease in measures of hemolysis with voxelotor. Furthermore, voxelotor was generally well tolerated. These results suggest that voxelotor has the potential to be disease-modifying by improving anemia and reducing hemolysis and their associated morbidity and mortality.
| Double targeting of abnormal erythropoiesis strikingly improves anemia in a thalassemia mouse model (abstract S148) - Presenter: Dr Antonella Nai – Italy
Conclusion: While Tfr2 haploinsufficiency does not impair systemic iron homeostasis, here we demonstrate that deletion of a single Tfr2 allele in the BM is sufficient to improve the hematological parameters of thalassemic mice. This finding paves the way toward a potential targeted therapy based on partial Tfr2 inhibition that might be beneficial for thalassemia (and potentially for other forms of anemia) without inducing defective hepcidin activation and iron overload. In addition, our results prove that targeting Tfr2 in combination with an anti-TMPRSS6 therapy may be a valuable therapeutic approach that strongly improves the thalassemic phenotype. However, Tmprss6 inhibition must be tightly controlled to avoid excessive iron restriction. Further experiments will allow setting up the optimal conditions.
| Treatment with Imetelstat Provides Durable Transfusion Independence in Heavily Transfused Non-Del(5q) Lower Risk MDS Relapsed/Refractory to erythropoietic stimulating agents (abstract S837) - Presenter: Dr Pierre Fenaux – France
TREATMENT WITH IMETELSTAT PROVIDES DURABLE TRANSFUSION INDEPENDENCE (TI) IN HEAVILY TRANSFUSED NON-DEL(5Q) LOWER RISK MDS (LR-MDS) RELAPSED/REFRACTORY (R/R) TO ERYTHROPOIESIS STIMULATING AGENTS (ESAS)
Conclusion: In high RBC transfusion burden patients with non-del(5q) LR-MDS R/R to ESA and naive to LEN/HMA, single-agent imetelstat yielded 8-week TI rate of 45%, with a median duration of 8.5 months (range 1.8-32.4). The 24-week TI rate was 26%. HI-E rate was 68%. All patients with IPSS-R intermediate and poor cytogenetic risk responded. Biomarker analyses of telomerase activity and mutation allele burden indicate an effect on the malignant mutant clone. These data support Part 2 of IMerge, Phase 3 placebo-controlled, randomized portion of the study, expected to open mid-2019.
| Labor is the most frequent outcome in the European Leukemia Net registry of patients with chronic myeloid leukemia and pregnancy (abstract S881) - Presenter: Dr Ekaterina Chelysheva – Russian Federation
Conclusion: Most pregnancies in CML female pts resulted in normal childbirth with no increased rate of birth abnormalities in spite of TKI use at conception even if treatments were mostly early stopped at implant (4-5 weeks). Different therapies were used during pregnancy when needed. The results in terms of conception/pregnancy may be valuable for the development of CML treatment schemes particularly considering the variety of disease status.
| Introduction of a new fixed-duration targeted therapy with venetoclax plus obinutuzumab in previously untreated patients with chronic lymphocytic leukemia (CLL) and coexisting comorbidities (abstract S149) - Presenter: Dr Kirsten Fischer – Germany
Conclusion: Fixed-duration VenG induced deep, high (<10-4 in 3/4 of pts and <10-6 in 1/3 of pts), and long lasting MRD-negativity rates (with a low rate of conversion to MRD-positive status 1 year after treatment) in previously untreated pts with CLL and comorbidities, translating into improved PFS.
| Genomic evidence of residual disease in patients in remission prior to stem cell transplant; fate or opportunity for early intervention? (abstract LB2600) - Presenter: Dr Christopher Hourigan - United States of America
Conclusion: Detection of an AML-associated variant using ultra-deep next-generation DNA sequencing in the blood of AML patients in CR prior to alloHCT was associated with increased relapse rate and inferior overall survival in those randomized to RIC. This study provides evidence that intervention for AML patients with MRD can result in improved survival.
Conclusion: D-VTd in induction prior to and consolidation after ASCT improved depth of response (sCR, ≥CR, and MRD negativity) and PFS with acceptable safety. The favorable benefit-risk profile supports the use of D-VTd in transplant-eligible NDMM. CASSIOPEIA is the first study to demonstrate the clinical benefit of daratumumab plus standard of care in transplant-eligible NDMM patients.
THE LANCET, VOLUME 394, ISSUE 10192, P29-38, JULY 06, 2019:
Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study