Eunice S. Wang, MD, on AML: Long-Term Results With Crenolanib Plus Chemotherapy
2022 ASCO Annual Meeting
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, discusses long-term phase II findings of a trial evaluating crenolanib plus chemotherapy in newly diagnosed adults with FLT3-mutant acute myeloid leukemia. The study showed a composite complete remission rate of 86%. With a median follow-up of 45 months, median overall survival has not been reached. A phase III trial is ongoing (Abstract 7007).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
We designed a phase II clinical trial evaluating crenolanib added to standard 7+3 intensive chemotherapy for adults with newly diagnosed FLT3 AML. The purpose of this study was to examine the efficacy of adding this novel FLT3 tyrosine kinase inhibitor to standard intensive chemotherapy based on prior results of single agent crenolanib activity in heavily pretreated relapse and refractory FLT3 mutant adult patients. Crenolanib is a pan-FLT3 inhibitor with activity against both the active and inactive formations of FLT3 and has activity against both FLT3, ITD, and TKD mutations.
We designed this study to combine it with intensive chemotherapy, for which the standard of care is currently midostaurin plus 7+3 chemotherapy. A total of 44 patients were enrolled on this study, 29 younger than equal to 60 years of age, and 15 older than 60 years of age. 91% of patients had de novo disease, 75% with FLT3 ITD mutations and 18% with TKD mutations. Overall, patients were enrolled in standard intensive therapy with physicians choice of anthracycline, daunorubicin, or idarubicin plus infusional cytarabine for 7 days, followed by crenolanib started at 24 to 48 hours after chemotherapy and continued until 72 hours prior to next chemotherapy cycle. Patients were allowed to get consolidation with high-dose cytarabine or go on to transplantation, followed by 12 months of maintenance crenolanib following either chemo or transplant.
The overall remission rate in this trial was 86%. Younger patients younger than are equal to 60 years of age had a CR/CRI rate of 90%, and individual's greater than or equal to 60 years of age had an overall response rate of 80%. At 45 months of long-term follow up, the event-free survival for all 44 patients enrolled in this trial was 45 months. The median overall survival was not reached. In younger patients younger than 60 years of age, the median overall survival was not reached, with 71% of patients alive at 3 years after enrollment on this study. The overall cumulative rate of relapse in patients was 33%, and 15% in patients younger than 60. Of note, patients undergoing transplantation in this younger cohort had similar cumulative rate of relapse than patients getting chemotherapy alone.
In conclusion, we think that this combination regimen shows high efficacy, safety, and tolerability as compared to standard 7+3 plus midostaurin. A phase III trial of this combination approach is currently accruing using midostaurin 7+3 as its control arm. Results of this trial are eagerly awaited.
The ASCO Post Staff
Sue S. Yom, MD, PhD, of the University of California, San Francisco, discusses a translational analysis from the NRG-HN002 study. This phase II trial established the feasibility of the tumor tissue–modified viral (TTMV) human papillomavirus DNA assay in clinical trial specimens. The goal is to use such an assay to measure tumor volume, levels of TTMV over the course of treatment, and the association of TTMV to treatment outcomes (Abstract 6006).
Paul G. Richardson, MD, of Dana-Farber Cancer Institute, discusses phase III findings from the DETERMINATION trial, which showed that, for patients with newly diagnosed multiple myeloma, lenalidomide, bortezomib, and dexamethasone (RVd) with or without autologous stem cell transplant (ASCT) and lenalidomide maintenance to disease progression resulted in the longest median progression-free survival reported for each approach, and a highly significant difference in progression-free survival in favor of early transplant. While overall response rates were similar, rates of MRD favored early transplant also, but toxicity was greater and quality of life was transiently but significantly diminished. No overall survival advantage has been observed to date (Abstract LBA4).
The ASCO Post Staff
Robert Hugh Jones, MD, PhD, of Cardiff University and Velindre Hospital, discusses results from an updated analysis of the FAKTION trial, which showed improved overall survival with fulvestrant plus capivasertib in women with metastatic estrogen receptor–positive breast cancer whose disease had relapsed or progressed on an aromatase inhibitor. The benefit may be predominantly in patients with PIK3CA/AKT1/PTEN pathway–altered tumors, a topic researchers continue to study in the phase III CAPItello-291 trial (Abstract 1005).
The ASCO Post Staff
Jenny S. Guadamuz, PhD, of Flatiron Health, discusses the use of telemedicine services in community oncology clinics for patients initiating treatments for 21 common cancers during the COVID-19 pandemic. Black, uninsured, non-urban, and less affluent patients were less likely to use telemedicine services. Although telemedicine may expand access to specialty care, the proliferation of these services may widen cancer care disparities if equitable access to these services is not ensured, according to Dr. Guadamuz (Abstract 6511).
The ASCO Post Staff
Sriram Yennu, MD, of The University of Texas MD Anderson Cancer Center, discusses the placebo response in patients with advanced cancer and cancer-related fatigue. His latest findings show that open-labeled placebo was efficacious in reducing cancer-related fatigue and improving quality of life in fatigued patients with advanced cancer at the end of 1 week. The improvement in fatigue was maintained for 4 weeks (Abstract 12006).