Megan Melody, MD, shares her thoughts on the important lymphoma abstracts being shared at the meeting
Health-Related Quality of Life of Patients With Advanced-Stage Classic Hodgkin Lymphoma Treated With BrECADD and eBEACOPP: Results From the HD21 Study
This post-hoc analysis of patient-reported outcomes (PROs) from the HD21 trial adds a meaningful survivorship perspective to the previously reported efficacy and safety advantages of BrECADD over eBEACOPP for newly diagnosed advanced-stage classic Hodgkin lymphoma (cHL). In approximately 1000 evaluable participants, health-related quality of life (HRQoL) was assessed longitudinally with the EORTC QLQ-C30
with up to 60 months of follow-up. Both regimens were associated with recovery in global health and quality of life, physical functioning, fatigue, and dyspnea after therapy; however, BrECADD was generally associated with smaller declines in QoL during treatment, particularly in global
health, fatigue, and dyspnea, as well as favorable longer-term functioning.
These findings are clinically relevant in a highly curable disease that frequently affects younger adults. When selecting a treatment regimen for this patient population, it is important to balance durable disease control with preservation of physical function and QoL. Strengths of this analysis include the randomized parent trial, well-balanced treatment groups, repeated longitudinal PRO assessments, adjustment for key baseline covariates, and follow-up extending to three years. Together with the established efficacy of BrECADD, these data support a patient-centered rationale for considering treatment burden alongside progression-free survival (PFS).
The applicability of these data to the US patient population is particularly interesting. Nivolumab-AVD (Nivo-AVD) is now the most common standard frontline approach for advanced-stage cHL in the United States. BrECADD has not been widely adopted as frontline therapy in the United States and is not currently a standard escalation strategy for patients with progression of disease after Nivo-AVD. eBEACOPP remains the more established escalation approach in this setting. Therefore, the direct frontline relevance of a BrECADD-versus-eBEACOPP comparison is limited in US practice, where eBEACOPP is now rarely selected upfront because of advances in novel agent-containing strategies. Nevertheless, the marked efficacy of BrECADD, together with better HRQoL and long-term functioning, raises an important question: should BrECADD be prospectively studied as a potentially less toxic alternative escalation regimen for select patients with cHL who require treatment intensification on Nivo-AVD.
Did Novel Agents Change the Curve? Survival Acceleration in Hodgkin Lymphoma After 2016: SEER Analysis
The therapeutic landscape of cHL has shifted significantly over the past 10 years, and this SEER-based study suggests that those changes are now visible at the population level. Evaluating 27,250 adults diagnosed between 2005 and 2022, the investigators found progressively better survival across successive treatment eras. Relative to 2005 to 2010, mortality was lower during the brentuximab vedotin era, with an adjusted hazard ratio HR) of 0.85, and lower still during the 2018 to 2022 era, with an adjusted HR of 0.76. The pace of HL-specific mortality reduction also accelerated after an estimated 2016 inflection point, increasing from 5.4% annually to 12.0% annually. Importantly, improvements extended across demographic and clinical subgroups, including patients aged 18 to 75 years.
The analysis is notable for its thoughtful effort to distinguish cHL-specific progress from general improvements in oncology care. Follicular lymphoma was used as a negative control, and the significant era-by-disease interaction supports a cHL-specific association between modern treatment eras and improved survival. In a disease that has long been considered highly curable, these findings reinforce that meaningful gains remain possible when effective novel agents are incorporated into treatment algorithms.
The likely drivers are multifactorial. Frontline BV-AVD and Nivo-AVD have expanded options for advanced-stage disease, while brentuximab vedotin- and PD-1 inhibitor-based salvage strategies (including BV-ICE, BV-Nivo, and pembrolizumab-GVD) have improved the ability to achieve disease control in the second-line setting. Although this is meaningful data, SEER lacks granular data on regimen selection, disease response, PFS, relapse timing, transplantation, comorbidity, and late toxicity and cannot determine whether the survival benefit arose primarily from first-line therapy, more effective salvage, improved transplant outcomes, or supportive care advances. Nonetheless, the magnitude and timing of the observed trend are encouraging.
This study also raises important questions regarding whether modern frontline regimens, including BV-AVD, Nivo-AVD, and BrECADD, reduce the proportion of patients who require second-line therapy compared with historical treatment regimens. Long-term follow-up is equally important to assess whether reduced cytotoxic chemotherapy exposure translates into fewer secondary malignancies. Repeating this analysis in five to 10 years, after broader adoption of Nivo-AVD as frontline standard of care for advanced-stage cHL, may provide a clearer view of the full impact of modern therapy.
Pirtobrutinib-First vs Brexucabtagene Autoleucel–First Sequencing Post Covalent BTK Inhibitor Failure in Mantle Cell Lymphoma: A Propensity-Matched Real-World Analysis
This is the largest real-world comparison to date of two key post-covalent BTK inhibitor (cBTKi) treatment strategies for mantle cell lymphoma (MCL): pirtobrutinib and brexucabtagene autoleucel (brexu-cel). Using the TriNetX Research Network, the investigators identified 274 patients across 112 US healthcare organizations, including 200 who received pirtobrutinib and 74 who received brexu-cel after cBTKi therapy. In unadjusted analyses, overall survival (OS) favored brexu-cel, with an HR for death of 2.01 for pirtobrutinib compared with brexu-cel. This difference persisted after propensity score matching, with an HR of 1.82 and median OS of 828 days in the pirtobrutinib group versus not reached in the brexu-cel group.
Although these data raise interesting insights, it is important to note a few limitations. The brexu-cel cohort was small, and TriNetX does not capture key disease- and treatment-specific variables, including MCL biology, prior lines of therapy, TP53 status, disease burden, response to prior therapy, bridging treatment, and manufacturing timelines.
In multivariable analysis adjusting for age, sex, hemoglobin, lactate dehydrogenase, chronic kidney disease, prior sepsis, and other fitness-related characteristics, the survival difference between these two treatment modalities was no longer statistically significant. Suggesting that patients able to proceed to CAR T-cell therapy may have more favorable performance status, disease kinetics, and organ function, as well as sufficient clinical stability to allow for referral to a treatment center, leukapheresis, manufacturing time, and tolerance of treatment-related toxicities. Therefore, the study provides useful comparative data but should not be interpreted as demonstrating a definitive survival advantage for brexu-cel over pirtobrutinib across all patients.
Clinically, both approaches remain important after cBTKi failure. Brexu-cel may provide durable disease control in eligible patients, whereas pirtobrutinib can be initiated rapidly and is more readily delivered in community practice. Prospective studies or carefully curated registries that incorporate disease kinetics, cellular therapy eligibility, PROs, toxicity, and access measures are needed to inform optimal sequencing.
Updated Results From the Phase 3 ECHO Trial of Bendamustine-Rituximab With or Without Acalabrutinib in Patients With Previously Untreated Mantle Cell Lymphoma: 50 Months of Follow-up
The updated ECHO analysis strengthens the evidence supporting incorporation of acalabrutinib into initial therapy for older adults with mantle cell lymphoma (MCL). At a median follow-up of 60.8 months, acalabrutinib plus bendamustine and rituximab (BR) prolonged median progression-free survival (PFS) to 72.5 months, compared with 47.8 months with BR alone, corresponding to a 32% reduction in the risk of progression or death (hazard ratio, 0.68; P=0.002). The analysis also showed delayed time to third-line therapy or death, with the median not reached in the acalabrutinib arm versus 73.8 months with placebo plus BR. This finding is notable because crossover to acalabrutinib was permitted after progression in the placebo group, yet the time-to-third-line endpoint continued to favor upfront acalabrutinib. These results support the concept that earlier BTK inhibition may provide clinical benefit that is not fully recaptured with delayed treatment.
Overall, these mature data demonstrate sustained PFS improvement with the addition of acalabrutinib to a BR backbone, as well as a clinically relevant post hoc assessment of time to third-line treatment. However, the absence of a statistically significant overall survival benefit remains important. Interpretation of time to third-line therapy should also be cautious because this was a post hoc endpoint and may be influenced by physician practice patterns, access to subsequent therapies, and crossover. In addition, the results apply specifically to patients aged 65 years or older receiving BR-based therapy and may not generalize to younger, transplant-eligible patients or to patients treated with emerging chemotherapy-sparing approaches.
Future studies should identify the biologic and clinical subgroups most likely to benefit from this approach, including patients with TP53 aberrations, blastoid or pleomorphic morphology, and high-risk MIPI scores. Comparative studies against other contemporary frontline strategies, together with analyses of minimal residual disease, quality of life, late toxicity, and sequencing after acalabrutinib exposure, will be essential to refine individualized first-line management.
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