Chr del(17)(p13.1)

In this population of pts with CLL with high-risk disease features predictive of need for earlier treatment, LEN resulted in a prolonged time to subsequent therapy, even in cases of LEN discontinuation. The incidence of gr ≥3 INFs and SN were as expected for this population supporting that LEN does not increase risk for these complications.

Del(13q) is associated with the longest survival rate, while the shortest survival is found in patients with del(17p). Even if MLPA has constraints, it may be used as the primary routine analysis in patients with CLL.

The most common treatment received for COVID-19 (for 32% of patients; 6/19) was sotrovimab. This first IA shows an 81.1% (95% CI, 71.3%–92.4%; n=53) acalabrutinib real-world continuation rate at 12 months in treatment-naïve patients with CLL. Future analyses are aiming at including retrospective data from around 40 clinical sites with approximately 350 eligible patients. Chronic lymphocytic leukemia, Real world data

P2, N=42, Active, not recruiting, Jennifer Woyach | Trial primary completion date: Dec 2022 --> Dec 2023

Median overall survival (OS) was similar among patients with monoallelic TP53-mutant MDS, multi-hit TP53-mutant MDS, and monoallelic TP53-mutant AML (median OS 440 days vs. 437 days vs. 440 days, respectively) (Panel A)... TP53-aberrant MDS and AML comprise a prognostically heterogeneous group of patients with inferior clinical outcomes, though the highest risk subgroup appears to be AML with multi-hit TP53 status or AML with TP53 VAF > 50%. There is high value in determining the allelic state and hit status at the time of diagnosis to help prognosticate and develop a long-term management plan. Allo-HCT improves median OS, though durable MRD-negative remission is rare.

With 76% of patients achieving uMRD in peripheral blood, this trial did not reach the prespecified activity threshold. Triple therapy with obinutuzumab, acalabrutinib, and venetoclax after an optional debulking with bendamustine regimen requires further evaluation in larger trials to define its value compared with double treatment with a BTK or BCL2 inhibitor combined with obinutuzumab or a combination of the two oral targeted drugs. Until these trials show a clear benefit, the use of the triple combination in routine practice cannot be recommended.

P3; Suspended --> Active, not recruiting

P3; Recruiting --> Suspended

P2, N=42, Active, not recruiting, Jennifer Woyach | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2022

Although Bruton’s tyrosine kinase inhibitors (BTKis; acalabrutinib, ibrutinib) are the current standard of care for CLL, the indefinite length of monotherapy required may result in cumulative clinical or economic toxicity and/or acquired treatment resistance. VAY736 + ibrutinib was well tolerated with an acceptable safety profile enabling dose expansion. Clinical activity was observed including multiple pts attaining uMRD status in blood and BM, allowing 6 to discontinue ibrutinib therapy for an extended period. These data provide clinical evidence of the potent anti-leukemia activity of VAY736 and the potential to safely discontinue ibrutinib or other BTKi by VAY736 add-on therapy.

Preliminary safety data with the 9.7-mo median follow-up suggest that zanubrutinib + venetoclax was generally well tolerated in this high-risk population, with no new safety signals identified and no TLS reported. Enrollment is ongoing; updated safety, efficacy, and biomarker data will be presented.

P2, N=42, Active, not recruiting, Jennifer Woyach | Trial completion date: Dec 2020 --> Dec 2022 | Trial primary completion date: Dec 2020 --> Dec 2021

Although the current WHO classification mainly focuses on morphological criteria for the diagnosis of OED, interobserver discrepancy appears in some instances of the OED diagnosis. Our immunohistochemical analysis supports a more accurate pathological diagnosis for OED in cases of low dysplastic changes or of differential diagnosis with non-dysplastic lesions.

TP53 mutations impacted OS irrespective of VAF. This finding can be used to update the definition of TP53 mutated CLL for clinical purposes.

The results indicate that B-CLL patients experience increased oxidative stress and the relative deficiency of the antioxidant defense system. Increased CD level was independently associated with greater likelihood of harboring CA.

In conclusion, we have shown that an increased percentage of M-MDSC cells producing IL-10 and TGF-β1 in CLL patients may be associated with the suppression of the immune response against CLL. It can be assumed that the increased percentage of M-MDSC with an intracellular expression of IL-10 and TGF-β1 may be used in the future as the factor defining the group of patients with shorter time to onset of treatment.

This updated and extended study further confirms that orelabrutinib is efficacious in treating r/r CLL patients with a higher CR rate, durable response and improved safety profiles. As a highly selective BTK inhibitor with favorable pharmacokinetic and pharmacodynamic properties, orelabrutinib provides a favorable therapeutic choice for patients with r/r CLL/SLL and a potential best candidate for combination therapy.

In conclusion, we identify that RS arises from CLL subclones through distinct mutational trajectories. Further molecular subclassification of RS, including genetic characterization of additional cases, and linking mutational data with clinical outcomes is ongoing and has potential to alter clinical classification and prognostication of RS.

Introduction Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) are treated with standard frontline immunochemotherapy (R-CHOP)...(2008) Leukemia 22:1440-2446). Further investigation and validation of these events and their corresponding targets will provide insight into the biology of rrDLBCL and may reveal novel therapeutic targets.

P2, N=42, Active, not recruiting, Jennifer Woyach | Trial completion date: Nov 2019 --> Dec 2020 | Trial primary completion date: Nov 2019 --> Dec 2020