The first-line, chemotherapy-free regimen of ibrutinib plus venetoclax showed ongoing efficacy after 2 years of follow-up in patients with chronic lymphocytic leukaemia (CLL). Patients with confirmed undetected measurable residual disease (uMRD) did not display MRD relapses, death, or progressive disease during the follow-up phase of the phase 2 CAPTIVATE trial. These results suggest that treatment-free remission may be achieved with a first-line, fixed-duration ibrutinib plus venetoclax regimen in patients with CLL .
The international, multicentre, phase 2 CAPTIVATE trial (NCT02910583) investigated an ibrutinib plus venetoclax regimen in patients with CLL (n=323), divided into a fixed-duration cohort and an MRD cohort. Patients received 3 cycles of oral ibrutinib (420 mg, daily), followed by 12 cycles of ibrutinib plus oral venetoclax (ramp-up to 400 mg daily). Dr Paolo Ghia (Università Vita-Salute San Raffaele, Italy) presented the 2-year follow-up results of the MRD cohort.
During cycle 16, patients with confirmed uMRD were randomised 1:1 to placebo (n=43) or ibrutinib monotherapy (n=43). Patients who did not achieve uMRD were randomised 1:1 to ibrutinib monotherapy (n=31) or ibrutinib plus venetoclax therapy (n=32). Notably, a high proportion of patients had high-risk features, such as unmutated immunoglobulin heavy-chain variable region gene (IGHV) (60%). The median post-randomisation follow-up was 24 months. Median treatment duration was 37 months in all patients.
No new disease-free survival (DFS) events had occurred since the primary analysis in patients with confirmed uMRD. The DFS rates remained at 95% and 100% for placebo and ibrutinib receivers, respectively. In addition, the overall study period displayed modest improvements in complete response (CR) rates for patients with confirmed uMRD compared with the pre-randomisation period (placebo 9%; ibrutinib 5%). Patients without confirmed uMRD showed larger improvements in CR rates, with ibrutinib receivers displaying a 22% improvement and ibrutinib plus venetoclax receivers demonstrating a 28% improvement. Furthermore, preliminary data suggested that patients who experience a progressive event may be re-treated with ibrutinib monotherapy. No new safety issues of the ibrutinib plus venetoclax regimen were observed.
- Ghia P, et al. First-Line Treatment with Ibrutinib (Ibr) Plus Venetoclax (Ven) for Chronic Lymphocytic Leukemia (CLL): 2-Year Post-Randomization Disease-Free Survival (DFS) Results from the Minimal Residual Disease (MRD) Cohort of the Phase 2 Captivate Study. Abstract 68, ASH 2021 Annual Meeting, 11–14 December.
Want to read more? Medicom has a featured interview with Dr Paolo Ghia (Università Vita-Salute San Raffaele, Italy) about the CAPTIVATE trial: Ibrutinib plus venetoclax show stunning efficacy in CLL.
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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