Adding the BCL2 inhibitor venetoclax (Venclexta) to chemoimmunotherapy was associated with worse outcomes and increased mortality in patients with newly diagnosed double-hit lymphoma, as shown in phase II results from a randomized trial.
Results Overview
Median progression-free survival (PFS) was 28.4 months for patients receiving dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) compared to just 7.7 months for those receiving the chemoimmunotherapy regimen plus venetoclax (HR 1.13, 95% CI 0.53-2.37, P=0.75), reported Dr. Jeremy S. Abramson from the Mass General Brigham Cancer Institute in Boston, along with colleagues.
Median overall survival was not achieved in either group; however, the 24-month overall survival estimates were 72% in the DA-EPOCH-R group versus 52% in the group that received venetoclax (HR 2.49, 95% CI 1.03-6.04, P=0.038), as noted in Lancet Haematology.
Trial Implications
The increased mortality (six deaths versus one in the DA-EPOCH-R group) led to the early termination of the trial. Adverse outcomes were primarily attributed to heightened hematologic toxicities and infections; as stated, “Venetoclax clearly enhances the toxicity of DA-EPOCH-R, and so this combination is not recommended.”
Results from the DA-EPOCH-R group show durable remissions in a significant number of patients and serve as an important reference for future studies.
Understanding Double-Hit Lymphoma
Double-hit lymphoma, characterized by a high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6, constitutes approximately 5% of newly diagnosed diffuse large B-cell lymphoma (DLBCL) cases. This subtype is notably aggressive and tends to have unfavorable outcomes following standard chemoimmunotherapy.
Intensive treatment strategies, such as DA-EPOCH-R, have shown potential in previous trials, although PFS remains below the desired outcomes seen in DLBCL patients without double-hit characteristics, indicating a pressing need for advancement.
Study Details
This cohort from the open-label ALLIANCE A051701 study consisted of 73 patients with new diagnoses of double-hit lymphoma and performance status scores of 0-2. Participants were recruited from 41 hospitals and outpatient clinics across the U.S. from October 2019 to September 2020 and were randomly assigned to receive either DA-EPOCH-R alone or DA-EPOCH-R plus venetoclax.
The median age of participants was 65 years, with 55% male and 89% white. Most patients (89%) had double-hit lymphoma featuring rearrangements of MYC and BCL2, with or without BCL6. The median follow-up period was 34.7 months.
During treatment, one death occurred in the DA-EPOCH-R group possibly related to dyspnea, while six deaths were reported in the DA-EPOCH-R/venetoclax group, predominantly due to sepsis and cardiac issues.
Additionally, four more patients in the DA-EPOCH-R/venetoclax group experienced late adverse event-related deaths, compared to one patient in the DA-EPOCH-R group.
Common grade 3-4 non-hematologic adverse events included febrile neutropenia, affecting 43% of the DA-EPOCH-R/venetoclax group versus 37% in the DA-EPOCH-R group.
In conclusion, given the data from this study, careful consideration should be given in the application of venetoclax in double-hit lymphoma treatment pathways.
Disclaimer: This content is for informational purposes only and does not constitute medical advice. Always consult with a healthcare professional for medical concerns.
Fuente: https://www.medpagetoday.com/hematologyoncology/lymphoma/122957
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