The final results of the phase 2 AMLSG 16-10 trial showed that younger and older patients with FLT3-ITD-mutated acute myeloid leukaemia (AML) benefitted from the addition of midostaurin to intensive chemotherapy. Furthermore, the occurrence of NPM1 mutations was a favourable prognostic factor. Older age, higher white blood cell (WBC) count, and higher FLT3-ITD allelic ratios increased the risk of unfavourable health outcomes .
Midostaurin is a first-generation, type I kinase inhibitor targeting FLT3-ITD and FLT3-TKD mutations . The single-arm, phase 2 AMLSG 16-10 trial (NCT01477606) included patients with newly diagnosed, FLT3-ITD-mutated AML up to 70 years of age (n=440) to investigate midostaurin plus induction chemotherapy, followed by allogeneic haematopoietic cell transplantation (HCT) and 1-year midostaurin maintenance therapy. A cohort of historical AMLSG trial participants (n=415) was used as control group. Dr Hartmut Döhner (Universitätsklinikum Ulm, Germany) mentioned that patients in the historical cohort had received their treatment approximately a decade earlier than patients in the AMLSG 16-10 trial. The primary endpoint was event-free survival. The key secondary endpoint was overall survival (OS).
The response rate to induction therapy was higher in the midostaurin cohort (CR/CRi 74.9%) than in the control cohort (64.6%). Moreover, the proportion of patients undergoing HCT in CR/CRi was higher in patients receiving midostaurin (45.2%) compared with control subjects (22.6%). The 5-year event-free survival and OS rates were significantly improved in the AMLSG 16-10 trial compared with the historical cohort. Patients <60 years of age treated with midostaurin had a 5-year OS rate of 49% versus 33% in controls. Patients between 61 and 70 years of age receiving midostaurin therapy showed a 5-year OS rate of 33%. Patients in the control group in this age category demonstrated an OS rate of 8% after 5 years.
Furthermore, NPM1 mutations had a favourable impact on event-free survival (HR 0.48; P<0.001), whereas older age (HR 1.17), higher WBC count (HR 1.21), and high FLT3-ITD allelic ratios (HR 1.19; P=0.072) were associated with an unfavourable effect on event-free survival. The therapy effect of midostaurin remained significant when allogeneic HCT was considered as a time-dependent variable.
Midostaurin was generally well tolerated. Respiratory, metabolic, and vascular adverse events were more frequently reported in older patients. However, Dr Döhner argued that underlying comorbidities may be the explanation for this outcome.
- Döhner H, et al. Midostaurin Plus Intensive Chemotherapy for Younger and Older Patients with Acute Myeloid Leukemia and FLT3 Internal Tandem Duplications. Abstract 692, ASH 2021 Annual Meeting, 11–14 December.
- Weisberg E, et al. Cancer Cell. 2002;1(5):433–443
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Table of Contents: ASH 2021
Letter from the Editor
ASH 2021 Highlights Podcast
Acute Lymphoblastic Leukaemia
New Interfant protocol includes blinatumomab for KMT2A-r ALL
Persistent disparities in ALL health outcomes
EWALL-INO: Inotuzumab ozogamicin promising as first-line therapy for BCP-ALL
UKALL 2003: Therapy de-escalation safe in low-risk MRD patients with ALL
Acute Myeloid Leukaemia
AMLSG 16-10: Long-term benefits of midostaurin for FLT3-ITD-mutated AML
Comparable effectiveness of CPX-351 and venetoclax plus HMA in older AML patients
Promising frontline triplet regimen for TP53-mutated AML
Encouraging results of novel triplet combination for AML
Heavily pre-treated FLT3-mutated AML population may benefit from novel triplet regimen
Benefits of eprenetapopt plus azacytidine for TP53-mutant MDS and oligoblastic AML
Improved risk stratification in MDS via gene-based scoring system
CAPTIVATE: Ibrutinib plus venetoclax shows ongoing efficacy in CLL
SEQUOIA: Zanubrutinib meets primary endpoint for treatment-naïve CLL/SLL
Investigational therapies superior to standard-of-care in double-exposed CLL
GRIFFIN: Sustained responses of daratumumab plus RVd in MM
MajesTEC-1: Teclistamab efficacious in heavily pre-treated MM
iStopMM: Smouldering MM highly prevalent in general population
Mechanisms of D-KRd treatment failure in MM identified
TRIMM-2: Favourable results of talquetamab plus daratumumab for MM
Second-line tisa-cel similar to standard-of-care for R/R aggressive non-Hodgkin lymphoma
Axi-cel improved event-free survival in R/R DLBCL
Axi-cel more effective but tisa-cel less toxic in DLBCL
POLARIX: Novel regimen superior to R-CHOP in DLBCL
Novel non-invasive biomarker ctDNA shows value in CNS lymphoma
Mechanisms behind TP53 mutations revealed in myeloproliferative neoplasms
JAK2V617F variant allele frequency prognostic of venous events in polycythaemia vera
Promising results of tacrolimus plus dexamethasone for ITP
Sustained remission after TPO-RA discontinuation in chronic ITP
Fitusiran meets primary endpoint in ATLAS-A/B trial
ATLAS-INH: Impressive results of fitusiran for haemophilia with inhibitors
rFVIIIFc establishes rapid tolerisation in haemophilia A with inhibitors
Reduced risk of Alzheimer’s disease in CHIP carriers
Lifelong patterns of clonal haematopoiesis revealed
Reduced risk of Alzheimer’s disease in CHIP carriers