CLL-118 A Phase 1 Study With the Novel B-Cell Lymphoma 2 Inhibitor BGB-11417 as Monotherapy or in Combination With Zanubrutinib in Patients With B-Cell Malignancies: Preliminary Data

Article

作者: Hilger, James ; Simpson, David ; Soumerai, Jacob D ; Tam, Constantine S ; Browett, Peter J ; Barca, Eva González ; Lasica, Masa ; Cheah, Chan Y ; Chan, Henry ; Fang, Yiqian ; Verner, Emma ; Opat, Stephen

CONTEXT:

B-cell lymphoma 2 (BCL2) is aberrantly expressed in many hematologic malignancies and promotes tumorigenesis. BGB-11417-101 (NCT04277637) is an ongoing, first-in-human, phase 1/1b dose-escalation/expansion study evaluating the safety, tolerability, maximum tolerated dose (MTD), and recommended phase 2 dose of oral BGB-11417, a potent, highly selective BCL2 inhibitor, alone or in combination with zanubrutinib, a BTK inhibitor, in patients with relapsed/refractory (R/R) B-cell malignancies.

DESIGN:

BGB-11417 (40, 80, 160, 320, or 640 mg once daily [QD]) with weekly or daily ramp-up to target dose was given as monotherapy or combined with zanubrutinib (320 mg QD or 160 mg twice daily) 8-12 weeks before BGB-11417. Dose-limiting toxicity was evaluated by Bayesian logistic regression. Adverse events (AEs) were reported per CTCAE v5.0.

RESULTS:

As of December 17, 2021, 58 patients received BGB-11417 (monotherapy=32; combination=26). Of patients receiving monotherapy, 26 with non-Hodgkin lymphoma (NHL; 17 diffuse large B-cell lymphoma, 6 follicular lymphoma, and 3 marginal zone lymphoma) received ≤640 mg and six with CLL/SLL received ≤160 mg; for those receiving combination treatment, 19 with R/R CLL/SLL received BGB-11417 ≤160 mg and seven with R/R MCL received ≤80 mg. MTD has not been reached. Median follow-up was 3.9 months (range=0.1-20.4). Two grade ≥3 AEs (neutropenia=1, autoimmune hemolytic anemia=1) occurred in combination cohorts. Twenty patients discontinued treatment (disease progression=17; AE=1; other=2). One high-risk patient with CLL (monotherapy) had laboratory tumor lysis syndrome (<2%) that resolved without intervention. Early data show that most patients had a reduction in the sum of products of perpendicular diameters; two patients with NHL (monotherapy) had responses (complete response=1). Patients with CLL/SLL had notable reductions in absolute lymphocyte counts at doses ≥1 mg; two responses (≥ partial response) occurred with monotherapy and 12 with combination treatment (≥ partial response + lymphocytosis).

CONCLUSIONS:

Preliminary findings suggest that BGB-11417 has promising efficacy and is tolerable at ≤640 mg as monotherapy and ≤160 mg combined with zanubrutinib. Dose escalation continues as MTD has not been reached. Enrollment is ongoing; data for Waldenström macroglobulinemia and treatment-naïve CLL/SLL are forthcoming.

2021-01-01·ACTA HAEMATOLOGICA

Current Treatment of Refractory/Relapsed Chronic Lymphocytic Leukemia: A Focus on Novel Drugs.

Review

作者: Smolewski, Piotr ; Robak, Tadeusz

Recently, the use of novel targeted drugs has changed the treatment paradigms in chronic lymphocytic leukemia (CLL). Among the several drugs used for the management of relapsed/refractory (R/R) CLL, Bruton tyrosine kinase inhibitors (ibrutinib and acalabrutinib), phosphatidylinositol 3-kinase inhibitors (idelalisib and duvelisib), B-cell lymphoma 2 inhibitor (venetoclax), and novel CD20 monoclonal antibodies have demonstrated the greatest improvements in survival among R/R CLL patients. However, patients with relapsed but asymptomatic CLL do not need immediate alternative treatment and should be observed until evident sign of progression. Among available approved treatments, venetoclax + rituximab for 24 months or ibrutinib as continuous therapy is recommended. Another, less recommended, option is idelalisib in combination with rituximab. The correct treatment selection depends on the type of prior therapy, response to previous treatment and side effects, presence of comorbidities, and the risk of drug toxicity. Allogeneic hematopoietic stem cell transplantation and investigational therapies such as chimeric antigen receptor-T-cell therapy are promising treatment options for high-risk patients, including those progressing after 1 or more targeted therapies. The present review discusses current treatment strategies for patients with R/R CLL.

Oncology Letters

Newer combination treatments for breast cancer coexisting with acute myeloid leukemia in the novel regimens era: A case report and literature review

Article

作者: Zhang, Jingnan ; Qiao, Shukai ; Guo, Xiaonan ; Xing, Lina ; Li, Yang ; Tian, Tian

The occurrence of acute myeloid leukemia (AML) with a simultaneous diagnosis of breast cancer (BC) is rarely reported in the literature. The present study reports the case of a 50-year-old female patient diagnosed with AML coexisting with metastatic BC. Following one cycle of treatment with azacytidine in combination with oral venetoclax for AML, the patient achieved complete remission with incomplete hematological recovery. In addition, the mass in the left breast was smaller following adjuvant chemotherapy. However, due to a refusal from the patient to accept an allogeneic hematopoietic stem cell transplantation (allo-HSCT), the patient succumbed 3 months after diagnosis due to septic shock from neutropenia following the third cycle of chemotherapy. Altogether, the present case report highlighted the application of venetoclax, an oral selective B-cell lymphoma-2 inhibitor, both in hematologic malignancies and solid neoplasms, as an effective therapeutic regimen. Considering the fatality rate associated with AML, allo-HSCT is the only available strategy that can be used to achieve the long-term survival of patients with AML and BC.

100 项与 B-cell lymphoma(Jenthera) 相关的药物交易

登录后查看更多信息