Startseite Kongressberichte & Archiv 59th ASH Annual Meeting and Exposition AML Oral Sessions Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Emerging Molecularly-Targeted Therapies in AML

616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Emerging Molecularly-Targeted Therapies in AML

Christoph Rollig, MD, MSC1*, Hubert Serve2, Andreas Hüttmann, MD3, Richard Noppeney, MD4*, et al. 

The authors of the study conclude that:

Mature follow-up data confirms the antileukemic efficacy of sorafenib in younger AML pts with and without FLT3 mutation. The addition of sorafenib to standard chemotherapy resulted in a significantly longer EFS and clinically relevant 36% risk reduction for relapse or death. Five pts need to be treated (NNT) to prevent one relapse or death at 3 years and six pts at 5 yrs. Exploratory analyses in relapsing pts show that survival after relapse is shorter after sorafenib which might be due to i) a higher rate of second SCTs and a higher incidence of haploidentical SCT despite the lower frequency of severe GVHD, most likely by chance and not explainable by systematic reasons and ii) a lower response to salvage treatment after sorafenib therapy. Despite these observations, primary sorafenib treatment led to an OS benefit with a 19% risk reduction for death which was not statistically significant since this phase II trial was not adequately powered to detect OS differences.

Keith Pratz, MD1, Mohamad Cherry, MD, MS2, Jessica K. Altman, MD3, Brenda W. Cooper, MD4, et al. 

The authors of the study conclude that:

In subjects with newly diagnosed AML, gilteritinib combined with intensive chemotherapy was well tolerated (MTD >120 mg/day) with seemingly high response rates in FLT3mut+ subjects.

Mahesh Swaminathan, MD1*, Hagop M. Kantarjian, MD1, Naval Daver, MD1, Gautam Borthakur, MD1, et al. 

The authors of the study conclude that:

Combination of quizartinib and AZA or LDAC is highly active among AML pts with FLT3-ITD mutation. ORR appear higher than expected with either agent alone. Clinically significant QTcF prolongation is infrequent. Accrual to the study continues.

Lynn Quek, FRCPath, DPhil, MBBS1,2*, Muriel David3*, Alison Kennedy, MSc4*, Marlen Metzner, MSc4*, et al. 

The authors of the study conclude that:

This study provides a paradigm of how deep clonal single cell analysis in purified hemopoietic compartments in sequential samples through therapy reveals clonal complexity and the impact of the selective pressure of therapy on clonal architecture. Furthermore, we gain insights into the functional heterogeneity of mIDH2 subclones in their ability to differentiate pre-and post-Enasidenib. Further analysis of this kind in a larger cohort of IDH2-inhibitor-treated patients would also provide insight to improve efficacy of this novel class of therapeutics, and design of combination therapies in AML and other cancers. Finally, this provides a platform for further study of the pathways mediating enasidenib resistance.

Courtney D. DiNardo, MD, MSc1, Stephane De Botton2*, Eytan M. Stein, MD3, Gail J. Roboz, MD4, et al. 

The authors of the study conclude that:

Ivosidenib monotherapy is well tolerated in patients with mIDH1 AML and other advanced hematologic malignancies. In a high-risk, molecularly defined R/R AML patient population with unmet medical need, ivosidenib induced durable remissions and improved patient outcomes. These findings support the role of ivosidenib as an effective, oral, targeted treatment for patients with mIDH1 AML.

Eytan M. Stein, MD1, Courtney D. DiNardo, MD, MSc2, Alice S. Mims, MD, MSCR3, Michael R. Savona, MD4

et al. 

The authors of the study conclude that:

Ivosidenib or enasidenib in combination with standard AML induction therapy is generally well tolerated. The slower platelet recovery observed in patients with mIDH2 sAML may reflect the reduced normal hematopoietic reserve in sAML patients; nevertheless, alternative dosing schedules for enasidenib with induction chemotherapy are being explored to see if delayed platelet recovery can be mitigated. Response rates thus far are encouraging, especially in patients with sAML, many of whom had received hypomethylating agent therapy. To further understand the quality of responses, analyses of minimal residual disease by mutational clearance are underway.