Recombinant factor VIII Fc protein (rFVIIIFc) therapy realised immune tolerance in approximately 2 out of 3 patients with severe haemophilia A and high-titre inhibitors who underwent immune tolerance induction (ITI) therapy for the first time. In addition, the agent displayed a swift time to tolerisation and no relapses occurred. These results add to the optimisation of ITI therapy with the purpose of eradicating inhibitors in these patients .
The international immune tolerance study (NCT00212472) showed that 40% of patients with severe haemophilia with inhibitors in the intent-to-treat population achieved immune tolerance, in a median time of approximately 22 months after rFVIIIFc treatment initiation. However, recent retrospective evidence suggested a higher success rate and rapid tolerisation in patients who underwent ITI therapy for the first time .
The current, global, prospective, verITI-8 study (NCT03093480) included 16 patients with severe haemophilia with inhibitors to administer first-time ITI therapy. The patients received rFVIIIFc therapy (200 IU/kg/day) for up to 48 weeks. If tolerisation was achieved within this timeframe, the patients entered a 16-week tapering period and a 32-week follow-up period. The primary endpoint was time to tolerisation. Treatment success was defined as negative Bethesda titres plus normal recovery (incremental recovery ≥66%) on 2 consecutive visits and rFVIIIFc half-life ≥7 hours. Dr Lynn Malec (Versiti Blood Research Institute, WI, USA) presented the final results.
Tolerisation was achieved in 63% of the patients in a median time of 11.7 weeks. In addition, the median time to the first negative inhibitor titre was 7.4 weeks, and the median time to normal recovery was 6.8 weeks (see Table). No relapses were observed in the patients who achieved tolerisation. Bypassing agents aPCC and rFVIIa were consumed by 25% and 31.3% of the patients during the ITI period, respectively. The median annual bleeding rates were 3.8 during the ITI period and 0.0 during the tapering and follow-up periods.
Table: Time to treatment success criteria 
IR, incremental recovery; ITI, immune tolerance induction
In total, 9 patients experienced at least 1 serious treatment-emergent adverse event (AE). However, none of these events was considered to be related to treatment. The serious treatment-emergent AEs included vascular device infections, contusions, and haemarthrosis. Importantly, no thrombotic events were reported.
- Malec L, et al. Efficacy of rFVIIIFc for First-Time Immune Tolerance Induction (ITI) Therapy: Final Results from the Global, Prospective VerITI-8 Study. LBA-5, ASH 2021 Annual Meeting, 11–14 December.
- Carcao M, et al. Haemophilia. 2021;27(1):19–25.
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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