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BTK inhibitors and anti-CD20 monoclonal antibodies for treatment-naive elderly patients with CLL.

ABSTRACT: Older patients account for the majority of patients with chronic lymphocytic leukemia (CLL), and so strategies for managing CLL in this population is of upmost importance. Inhibition of Bruton's tyrosine kinase (BTK) has been a successful therapeutic strategy in CLL, and the first-generation BTK inhibitor ibrutinib has been shown to be superior to standard chemoimmunotherapy in multiple studies specifically targeting older patients. A second-generation BTK inhibitor, acalabrutinib, has also been studied in CLL, and has recently been granted breakthrough designation by the United States Food and Drug Administration. One ongoing question is whether the addition of anti-CD20 monoclonal antibodies improve response or response durability with BTK inhibitors. In this review, we will discuss clinical trials of ibrutinib and acalabrutinib in older patients with CLL, and the possible contributions of anti-CD20 antibodies to these therapies.

SUBMITTER: Rogers A

PROVIDER: S-EPMC7092382 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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BTK inhibitors and anti-CD20 monoclonal antibodies for treatment-naïve elderly patients with CLL.

Rogers Andrew A Woyach Jennifer A JA

Therapeutic advances in hematology 20200323

Older patients account for the majority of patients with chronic lymphocytic leukemia (CLL), and so strategies for managing CLL in this population is of upmost importance. Inhibition of Bruton's tyrosine kinase (BTK) has been a successful therapeutic strategy in CLL, and the first-generation BTK inhibitor ibrutinib has been shown to be superior to standard chemoimmunotherapy in multiple studies specifically targeting older patients. A second-generation BTK inhibitor, acalabrutinib, has also been ...[more]

PMID: 32231778

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Project description:CD20-negative diffuse large B-cell lymphoma (DLBCL) is a rare type of lymphoproliferative disorder characterized by a high degree of aggressiveness, a tendency for extranodal invasion and chemotherapeutic resistance. CD20-negative DLBCL originating from the nervous system is rarer. In primary central nervous system lymphoma (PCNSL), >90% of cases are histologically classified as DLBCL. The present study reports the case of a 65-year-old female with CD20-negative PCNSL, whose primary clinical symptom was a persistent headache. Serum tests for human immunodeficiency virus, Epstein-Barr virus-DNA, human herpesvirus 8, hepatitis B and hepatitis C were negative. Cranial magnetic resonance imaging suggested multiple intracranial occupancies. The neoplastic cells were found to be positive for CD19, CD79α, Bcl-2 (~92%) and c-Myc (~50%), while showing negative results for CD20, CD138, programmed cell death protein 1 (PD-1) and programmed cell death receptor 1 ligand 1 (PD-L1). The Ki-67 proliferation index was >80%. In the tumor microenvironment, <10% of the tumor-associated macrophages expressed PD-L1. The number of PD-1-positive tumor-infiltrating lymphocytes was 30-40 cells according to high-power field microscopy. The patient's disease progressed during methotrexate-based treatment, leading to a change in the treatment regimen to the Bruton tyrosine kinase inhibitor, zanubrutinib, combined with the anti-PD-1 monoclonal antibody tislelizumab. After two courses of the combined treatment, the patient achieved complete remission (CR) and continued to receive consolidation treatment. In the 20 months of follow-up since CR was achieved, the patient's general condition was good and the disease was in continuous remission. The present case report and literature review show that a combination of drugs targeting different mechanisms may be used to treat PCNSL to prolong patient survival time. The mechanism of the enhanced efficacy of a combination of the two drugs may be related to the enhancement of antitumor T-cell immune responses and reversal of T-cell immune metabolic dysfunctions by the inhibition of glycolysis.

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Dataset Information

BTK inhibitors and anti-CD20 monoclonal antibodies for treatment-naive elderly patients with CLL.

Publications

BTK inhibitors and anti-CD20 monoclonal antibodies for treatment-naïve elderly patients with CLL.

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