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外文期刊>Journal of the advanced practitioner in oncology
>Hematologic Malignancies: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner: The Advanced Practitioner Perspective: Novel BCL2 Inhibitor Shows Activity in CLL in Phase I Trial, By Alice Goodman
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Hematologic Malignancies: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner: The Advanced Practitioner Perspective: Novel BCL2 Inhibitor Shows Activity in CLL in Phase I Trial, By Alice Goodman
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机译：Hematologic Malignancies: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner: The Advanced Practitioner Perspective: Novel BCL2 Inhibitor Shows Activity in CLL in Phase I Trial, By Alice Goodman
The novel, selective BCL2 inhibitor lisaftoclax (APG-2575) has shown activity in the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) in a phase I study reported at the 2021 ASCO Annual Meeting.1 Preliminary data suggest that lisaftoclax stands out for its favorable safety profile and rapid time to response. “APG-2575 is well tolerated in doses up to 1,200 mg/d, with infrequent grade 3 to 4 treatment-related adverse events. No tumor-lysis syndrome or dose-limiting toxicity has been observed in this trial, and the maximal tolerated dose has not been reached. The trial suggests proof of concept in these preliminary data, with an objective response rate of 80% in relapsed or refractory CLL and activity in other hematologic malignancies,” said Sikander Ailawadhi, MD, of the Mayo Clinic, Jacksonville, Florida. “This new drug is a potential alternative for patients with relapsed or refractory CLL and other hematologic malignancies where BCL2 is a driver. It has a shorter daily ramp-up schedule [than venetoclax] that may be more patient-centric and convenient, as well as a preliminary favorable safety profile,” he continued. The Advanced Practitioner Perspective: The efficacy of the BCL2 antagonist venetoclax in both treatment-naive and previously treated CLL is well established. Lisaftoclax represents a novel oral BCL2 antagonist currently in development with no concerning safety signals in this phase I data. The adverse event profile is similar to that of venetoclax, including fatigue, neutropenia, diarrhea, and anemia, but what is perhaps most notable is the absence of any laboratory or clinical tumor lysis syndrome (TLS), despite not only classification of study patients with CLL/SLL as either intermediate or high risk for TLS, but also a dose escalation protocol occurring over 5 days as opposed to 5 weeks (as recommended with venetoclax). Although still in the early stages of study, advanced practitioners should be aware of lisaftoclax, as it may offer an additional choice of BCL2 antagonist with a decreased risk of TLS, which could theoretically translate into decreased need for hospitalization and decreased number of clinic visits and lab draws for TLS monitoring while undergoing dose escalation. While this phase I data is encouraging for another potential tool to treat CLL, longer-term studies with larger numbers of patients, including phase II and phase III trials, are needed before this data impacts how advanced practitioners counsel patients with relapsed CLL on treatment options outside the context of a clinical trial.
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