Spotlight ASH 2020: BTKi dark tide surges

the | Leaf BTK, or Bruton's tyrosine kinase, is an important signaling molecule of the B cell-borne pathline, expressed at various stages of B-cell development, participates in regulating the proliferation, differentiation and apoptosis of B-cells, plays an important role in the survival and diffusion of malignant B-cells, and is a research hot spot for B-cell tumors and B-cell-type immune diseases.
: Currently, there are four products available for BTK inhibitors: Ibtini, Acatini, Tirabrutinib and Zebtini.
, however, market performance remains the only one in Ibdini, which will pass the $10 billion mark by 2020 and continue to be the "fairy leader" in BTK.
is the so-called, red is not much, the stars are trying to pull Ibtini down the altar.
at the 62nd annual meeting of the American Society of Hematology (ASH) next month, Ibdini, Acadini, Zebtini, Ebdini, and the second-generation BTK inhibitor LOXO-305 have all brought their own results.
You sing me on stage: the co-priced BTKi research results as the first immortal Ibdini, although there are some problems such as selectivity, but firmly control the pulse of the market, also did not stop their own way forward.
So far, Ibtinib has been approved for six adaptations, including chronic lymphocytic leukemia, small lymphocytic lymphoma, set cell lymphoma, Fahrenheit globulinemia, transplant anti-host disease and marginal lymphoma, and is also exploring joint drug use to solve its own drug resistance problems.
Ibdini at this session has also brought many research successes, but more long-term follow-up data.
Acatinib, Zebutini and Ebdinib are also among the many studies published at this ASH conference, limited to the length of which we cannot include in all of them, and only a select comparison of these drugs on the market or upcoming.
source: NextPharma Database I, CLL/SLL: Ibtini vs Ocatini vs Zebtini vs Ebtini Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) is an important area of BTK products, and three of the four products listed cover the adaptation, which is in the domestic market approval stage, and Obudini is also the first field with MCL.
1. Ibtini Long-Term Efficacy of First-Line Ibrutinib Treatment for Chronic Lymphocytic Leukemia (CLL) With 4 Years of Follow-Up In Patients With TP53 Aberration del (17p) or TP53Mutation: A Pooled Analysis From 4 Clinical Trials Ibdinie showed significant PFS and OS benefits in several random III.phase III. studies of CLL/SLL first-line therapy.
reports based on single-drug or combined therapy further demonstrate that ibutonib has good PFS benefits in patients with first-line and recurring/reframable TP53 abnormalities, but long-term prognosis data are limited.
by collecting 4 clinical data PCYC-1122e, PCYC-1130, ECOG1912 and RESONATE-2, the researchers conducted a summary analysis to assess the long-term efficacy and safety of Ibdinib's first-line treatment in patients with TP53 abnormal CLL.
89 patients were eventually included in the combined analysis.
45 patients received Ibtinib monotherapy and 44 patients received Ibtinib combined anti-CD20 medication.
50-month follow-up time, the middle PFS did not reach (95% CI: 67 months-not estimable; Figure 1A).
48 months, the PFS rate was 79% and the OS rate was 88% (Figure 1B).
duration of Ibtinib treatment was 46 months.
≥ level 3 include infections, high blood pressure, atrial fibrillation, and haemorrhage.
follow-up of an average of 4 years, Ibdinib's first-line treatment of TP53 abnormal CLL showed sustained efficacy, showing higher PFS and OS.
although there is still a risk of progress in patients with TP53 abnormalities, Ibdinib's first-line treatment has partially overcome the poor prognostics of this high-risk group, with four-year PFS and OS rates of 79% and 88%, respectively.
source: AHA 2020, next to Outcomes of First-Line Ibrutinib in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and High-Risk Genomic Features with up to 6.5 Years Follow-up: Integrated Analytics of Phase Two 3 Studies (RESONATE-2and iLLUMINATE) At this year's ASH conference, Ibdini still has a lot more than the data analysis above.
In this analysis, the researchers again included the RESONATE-2 study and, in conjunction with another Phase III. study (iLLUMINATE), aggregated and analyzed the prognostic results of 498 patients treated with ibr or phenyrate nitrogen mustard (clb) for a medium follow-up time of 49.1 months.
results showed similarities between PFS and ORR benefits in patients with/without high-risk genomic characteristics, and confirmed that ibr-based therapy had significant PFS and ORR benefits compared to ±obinutuzumab, and that the therapeutic effect was independent of cytogenetic and mutation risk characteristics, including unmortuminated IGHV, NOTCH1 mutations, and del (17p)/TP53/BIRC3 mutation classification.
Real-World Outcomes of Patients Treated with Single-Agent Ibrutinib for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Adverse events such as A System Review and Meta-Analysis infections are the main causes of Ibtini's suspension.
real-world studies suggest that adverse events associated with ibdinib are more common in clinical practice than in clinical trials, and dose reductions and drug suspensions are more common, despite conflicting evidence.
indeed, at this ASH session, studies have also revealed that Ibdinib can still benefit from long-term treatment after suspension.
the study aims to systematically review and analyze the true toxicity and toacces of Ibdinib's treatment of CLL patients, sifting through 25 full-text studies from 4,458 headings and abstracts for Meta analysis.
the rate of any bleeding was 5.4-54.1 times/100 years, the rate of severe bleeding was 0-6.4 times/100 years, the infection rate was 2.5-26.0 times/100 years per 9.2-49.8 times/100 years.
Through meta-analysis of medium-quality studies, the atrial fibrillation risk summary per 100 people/year is estimated at 7.0 (95% CI 5.8, 8.2), with the probability of dose reduction ranged from 15.1 to 26.8 doses per 100 people per year, and the dose reduction did not affect the results.
6.4 to 55.2 drug stops (100 people/year), the most common cause of drug suspension is adverse events.
important to note that the study has many limitations due to the heterogeneity determined by the patient's characteristics and results.
other research developments in this area, please participate in the SUMMAR website summary.
2. Akatini Acalabrutinib Vs Idelalisib Plus Rituximab or Bendamustine Plus Rituximabin Relapsed/Refractory Chronic Lymphocytic Leukemia: Ascend Final Results acatyla is a next-generation, highly selective co-priced BTK inhibitor that has been approved by the FDA for use in patients with chronic lymphocytic leukemia (CLL), including relapse/refratic (R/R) CLL.
the effectiveness and safety of the separate use of acala and Adlani (Id) Galitoxi monoanti (R) or benzomostin (B) plus R (BR) in patients with R/R CLL in a pre-existing ASCEND interim analysis, the final results of this study were reported.
the randomized, multi-center, open-label Phase III. study recruited 310 patients (acala, n=155; IdR, n=119; BR, n=36), with a medium age of 67 years (del (17p) 16%, del (11q) 27%, Rai 3/4 42%).
22 months of median follow-up, Akatini significantly extended the PFS assessed by the researchers compared to IdR/BR (median: NR vs. 16.8 m; HR:0.27, P-lt;0.0001);
common adverse events (AEs) are shown in the table below, AEs are 16% (acala), 56% (IdR) and 17% (BR) respectively.
other research developments in this area, please participate in the SUMMAR website summary.
3. Zebtini zebutinib in the current ASH is also about to announce a number of research advances in the CLL/SLL field, in order to facilitate drug-to-drug comparison, this article describes only monodring therapy research, other research progress in this field can be found in the ASH website summary.
Efficacy and Safety of Zanubrutinib in Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with del (17p): Follow-Up Results From Arm of SEQUOIA (BGB-3111-304) Trial Zebutini SEQUOIA Research Queue C (Arm C) is a large cohort study for TN CLL/SLL patients carrying del (17p).
10-month data analysis of the mid-level follow-up was published in 2019, and this report provides the latest security and effectiveness analysis for this queue.
as of April 15, 2020, the medium follow-up time for 109 patients in the group was 18.2 months, and 97 patients were still receiving Zebtinib treatment.
optimal total remission rate (ORR) was 94.5% (3.7% cr for complete remission of the disease or incomplete bone marrow recovery, 87.2% partial remission of the disease ( PR), 3.7% PR with increased lymphocytes, 4.6% disease stabilization, 0.9% disease progression).
non-progressive lifetime (PFS), reaction duration (DoR), and overall lifetime (OS) data are not yet mature.
Through long-term follow-up, ≥10% of treatment-related adverse events (AEs) include bruising, upper respiratory tract infections, neutral granulocyte reduction/neutral granulocyte reduction, diarrhea, nausea, constipation, rash, back pain, cough, joint pain, and fatigue.
follow-up results of zebtinib monotherapy del (17p) TN CLL / SLL pts showed that the response was highly persistent in the high-risk group, with an estimated 18-month PFS, DoR and OS rates of 88.6%, 84.0% and 95.1%, respectively, and generally good resistance due to low drug suspension due to AE.
data support Zebtinib's potential effectiveness in first-line treatment in patients with high-risk diseases.
4. Orelabrutinib (ICP-022) is also a new, highly selective irreversible BTK inhibitor and is currently in the review phase of domestic listing applications.
previously reported I/II data show that abteni has high bio-utilization in R/R CLL/SLL patients, with an oral 150 mg per day and a BTK occupancy rate of approximately 100% within 24 hours, demonstrating excellent safety and efficacy.
Updated Results from the Phase II Study of Orelabrutinib Monotherapy in Chinese Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small CellLeukemia presented a long-term post-treatment evaluation of patients with R/R CLL/SLL in China.
the study was an open, multi-center, Phase II study that included 80 patients with R/R CLL (n=70)/SLL (n=10) with a medium follow-up time of 14.3 months. <br/