ArticleBlood advances2021
Outcomes of patients with CLL sequentially resistant to both BCL2 and BTK inhibition.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy and Effectiveness Outcomes of Treatments for Double-Exposed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Patients: A Systematic Literature Review.Cancer medicine · 2024Pooled it
- Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study.Lancet (London, England) · 2023Trial
- Adding Umbralisib and Ublituximab (U2) to Ibrutinib in Patients with CLL: A Phase II Study of an MRD-Driven Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- High-risk single-refractory and double-refractory chronic lymphocytic leukemia: feasibility and impact of alloHCT.Blood advances · 2026Article
- Australasian chronic lymphocytic leukaemia consensus statement: 2026 update.Internal medicine journal · 2026Article
- Real-world clinical outcomes in patients with CLL previously treated with covalent BTKi and BCL2i regimens.Blood neoplasia · 2026Article
- Preclinical and clinical efficacy of the HDAC6 inhibitor ricolinostat in combination with BCR pathway inhibitors in relapsed/refractory chronic lymphocytic leukemia.Blood cancer journal · 2026Article
- Existing and emerging strategies for fertility preservation in female patients with leukemia.Frontiers in endocrinology · 2026Review
- An Update on Clinically Advanced PROTAC Degraders and Their Synthesis.Molecules (Basel, Switzerland) · 2025Review
- Management of Relapsed and/or Refractory Chronic Lymphocytic Leukemia.Hematology/oncology clinics of North America · 2025Review
- Characteristics and outcomes of patients with double refractory and double exposed chronic lymphocytic leukemia.Blood advances · 2025Article
- Cholesterol homeostasis and lipid raft dynamics at the basis of tumor-induced immune dysfunction in chronic lymphocytic leukemia.Cellular & molecular immunology · 2025Article
- Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.American journal of hematology · 2025Review
- Review
- Chimeric Antigen Receptor-T Cells in the Modern Era of Chronic Lymphocytic Leukemia Treatment.Cancers · 2025Review
- Clinical Outcomes in Patients With CLL Treated With BTKi at a Large US Cancer Center.Advances in hematology · 2025Article
- Article
- Treatment Sequencing in Chronic Lymphocytic Leukemia in 2024: Where We Are and Where We Are Headed.Cancers · 2024Review
- Venetoclax-rituximab is active in patients with BTKi-exposed CLL, but durable treatment-free remissions are uncommon.Blood advances · 2024Article
- Innovative Combinations, Cellular Therapies and Bispecific Antibodies for Chronic Lymphocytic Leukemia: A Narrative Review.Cancers · 2024Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Covalent Bruton tyrosine kinase inhibitors (BTKi's) and the B-cell lymphoma 2 (BCL2) inhibitor venetoclax have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL), especially those with biologically adverse disease. Patients with CLL resistant to their first targeted agent (TA) can be effectively treated with the alternative class. However, relapses are expected with second-line TA therapy, and the clinical challenge of double class-resistant disease is now emerging with increasing frequency. To define the characteristics and outcomes of patients with double class-resistant disease, we retrospectively analyzed 17 patients who developed progressive disease (PD) on both TA classes for CLL (venetoclax, then BTKi, n=12; BTKi, then venetoclax, n = 5). The cohort was heavily pretreated (median lines of prior therapy, 4) and enriched for adverse disease genetics (complex karyotype, 12 of 12 tested [100%]; del(17p)/TP53 mutations, 15 of 17 [88%]). The median time to progression on prior venetoclax was 24 months (range, 6-94 months) and was 25 months (range, 1-55 months) on prior BTKi. Progression on second-line TA was manifest as progressive CLL in 11 patients and as Richter transformation in 6. The median overall survival after progression on second-line TA was 3.6 months (95% confidence interval, 2-11 months). Patients with double class-resistant CLL have a dismal prognosis, representing a group of high unmet need.
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