2024 ASCO Direct™ Washington DC: Dr Dunleavy Discusses Two Key Studies in Lymphoma
Presenter
Kieron Dunleavy, MD, Medstar Georgetown University Hospital
Conference:
2024 ASCO Direct™ Washington DC
In his presentation focused on lymphoma updates at the 2024 ASCO Direct™ Washington DC conference, Dr Kieron Dunleavy from Medstar Georgetown University Hospital highlighted two key abstracts from this year’s Annual Meeting of the American Society of Clinical Oncology (ASCO).
GHSG HD21 Trial: BrECADD Versus eBEACOPP For Advanced Hodgkin Lymphoma
The Bottom Line
The GHSG HD21 trial introduced a new chemotherapy regimen, BrECADD, for patients with advanced-stage classical Hodgkin’s lymphoma. This regimen aimed to retain the effectiveness of the standard eBEACOPP regimen, while significantly reducing its associated toxicities. The results were compelling: BrECADD proved to be less toxic and equally effective, offering a 4-year progression-free survival (PFS) rate of 94.3% for patients. Dr. Kieron Dunleavy highlighted, “BrECADD is a game-changer, demonstrating not just non-inferiority but a better quality of life for patients due to reduced side effects.”
Background
Advanced-stage Hodgkin’s lymphoma traditionally requires aggressive chemotherapy regimens such as eBEACOPP, which can carry significant toxicities, including neuropathy, gonadal (sexual) dysfunction, and a requirement for blood transfusions. The GHSG HD21 trial was designed to test whether BrECADD, a modified regimen, could offer comparable efficacy while reducing toxicity. The BrECADD regimen replaces two drugs, bleomycin and vincristine, known for their pulmonary and neurotoxic side effects, with brentuximab vedotin, and incorporates a less gonadotoxic drug, dacarbazine, instead of procarbazine.
Trial Design and Patients
This trial was an international, open-label, phase III study involving 1,500 patients under 60 years of age with previously untreated, advanced-stage classical Hodgkin’s lymphoma. Patients were randomized to receive either BrECADD or eBEACOPP for 4–6 cycles. A PET scan after two cycles of therapy was used to guide the subsequent treatment intensity. Key study objectives were to demonstrate:
Superior tolerability profile for BrECADD, as measured by treatment-related morbidities (TRMB).
A similar (non-inferior) efficacy of BrECADD compared to eBEACOPP, with progression-free survival (PFS) as the primary endpoint.
Dr. Dunleavy noted, “This trial was designed to directly address the trade-off between toxicity and efficacy, focusing on outcomes that matter most to patients.”
Main Trial Results
Results from the HD21 trial reported at ASCO 2024 showed several important findings:
Toxicity: BrECADD showed a significant reduction in acute and severe treatment-related adverse events: Only 42% of BrECADD patients experienced significant TRMB compared to 59% of eBEACOPP patients (relative risk: 0.72, p<0.0001). Specifically, substantive reductions were observed in:
Peripheral neuropathy: Neuropathy of Grade 2 severity was reduced from 14% to 6%.
Blood transfusions: Red blood cell transfusions dropped from 52% to 24%, and the need for platelet transfusions was reduced from 34% to 17%.
Gonadal dysfunction: The recovery rates for patient’s gonadal function were much higher with BrECADD (87% in men and 96% in women) compared to eBEACOPP.
Efficacy: With a hazard ratio of 0.63, BrECADD demonstrated equivalent (non-inferior) efficacy, as assessed by PFS, at the interim analysis. After 48 months of follow-up, BrECADD achieved a 4-year PFS of 94.3%, and most patients (64%) required only four cycles of treatment.
Overall Survival: No significant differences were observed between the two groups, underscoring the equivalent efficacy of the BrECADD regimen, despite reduced toxicity. Dr. Dunleavy suggested, “This is a critical step forward. BrECADD maintains efficacy while addressing long-term survivorship concerns like infertility and neuropathy.”
“For young patients with Hodgkin‘s lymphoma, these findings are incredibly important. The ability to recover gonadal function and minimize neuropathy changes the conversation about survivorship…”
Conclusions and Faculty Insights
Overall, the HD21 trial establishes BrECADD as a safer, equally effective alternative to eBEACOPP, with Dr. Dunleavy predicting, “I think we’ll see a major shift away from eBEACOPP.” He further noted that, while immune checkpoint inhibitors and other novel agents are emerging in the frontline setting, BrECADD offers a promising new standard for chemotherapy in advanced Hodgkin lymphoma.
Rituximab Maintenance After First-Line BR in Mantle Cell Lymphoma
The Bottom Line
The role of rituximab maintenance therapy after first-line (1L) bendamustine-rituximab (BR) treatment in mantle cell lymphoma (MCL) has been a subject of debate. A new observational study demonstrated significant survival benefits for patients who received rituximab maintenance, particularly those achieving complete response (CR) after BR. “This study underscores the importance of maintenance therapy in prolonging outcomes and potentially reshaping MCL treatment strategies,” noted Dr. Dunleavy.
Background
Bendamustine-rituximab (BR) is a standard regimen for patients with MCL, especially for older or less fit patients. Previous studies showed survival benefits with rituximab maintenance following other chemotherapy regimens, such as R-CHOP or high-dose R-DHAP, however, its role after the BR regimen remained uncertain. This large, multicenter cohort study sought to clarify this issue with an analysis of long-term outcomes for patients receiving rituximab maintenance after BR.
Trial Design and Patients
The study analyzed 796 patients with MCL treated with 1L BR, excluding those who underwent an autologous stem cell transplant or who received novel agents like BTK inhibitors. Among the 613 eligible patients in the study, 318 received rituximab maintenance, and 295 did not receive maintenance therapy. Outcomes were assessed using landmark analysis starting three months after BR. Key endpoints included event-free survival (EFS), time to progression or retreatment after second-line therapy (EFS2), and overall survival (OS).
Main Trial Results
Event-Free Survival (EFS):
Patients with a complete response (CR) after BR had a median EFS of 5.1 years with rituximab maintenance versus 2.6 years without (HR: 0.56).
Patients with a partial response showed improvement, but results were less definitive due to the smaller number of patients examined.
Second-Line Survival (EFS2):
Among patients with a CR, 5-year EFS2 was 62% for those receiving maintenance rituximab, as compared to 46% without it.
Overall Survival (OS):
5-year OS rates for CR patients were 64% with maintenance rituximab, versus 46% without (HR: 0.48).
“For patients achieving complete response, rituximab maintenance offers a clear survival advantage, making it an essential part of the treatment paradigm.”
Adverse Events and Toxicities
While not detailed in this study, Dr Dunleavy noted that rituximab maintenance has been generally well-tolerated, with low rates of infusion-related reactions and manageable infections, based on prior studies.
Conclusions and Faculty Insights
Overall, Dr Dunleavy noted this study highlights the potential of rituximab maintenance to extend survival for MCL patients after BR, especially for those who achieve a CR. “It’s a compelling argument for maintenance therapy,” he said, while also acknowledging the need for prospective randomized trials to confirm these findings and clarify benefits for patients who achieve a lesser PR to initial BR treatment.
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Speaker Disclosure Information: Dr Dunleavy reported no relevant disclosures for this presentation.