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2024 EHA Mantle Cell Lymphoma Updates
Key Updates in Mantle Cell Lymphoma From the 2024 EHA Congress

Released: July 23, 2024

Expiration: July 22, 2025

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Key Takeaways
  • In the phase III ECHO trial, frontline acalabrutinib plus bendamustine and rituximab (BR) significantly prolonged progression-free survival vs placebo plus BR in older patients with mantle cell lymphoma (MCL), although the acalabrutinib arm had higher rates of COVID-19–related adverse events; much of this study was performed before COVID-19 therapies and vaccination were widely available.
  • Updated phase I/II trial data suggest that fixed-duration treatment with glofitamab, a CD3 x CD20 bispecific antibody, is highly active in patients with heavily pretreated MCL and warrants further study.
  • The MCL Biobank observational study reported that among patients newly diagnosed with MCL, approximately half of those assigned to watchful waiting did not need treatment for 2 years.

At the 2024 European Haematology Association (EHA) Congress, important results were reported from multiple clinical trials and epidemiologic studies of mantle cell lymphoma (MCL). In this commentary, I share my thoughts on the main takeaways and clinical implications of the top studies presented.

Notable clinical trial results in frontline MCL include:

  • A late-breaking abstract sharing positive results from the phase III ECHO (ACE-LY-308) trial. ECHO demonstrated that adding acalabrutinib, a second-generation covalent BTK inhibitor, to bendamustine and rituximab (BR), our current standard of care, significantly prolonged progression-free survival (PFS) vs placebo plus BR in older patients with previously untreated MCL. This study was performed in the depths of the COVID-19 pandemic, and we saw more COVID-19–related adverse events (AEs) with acalabrutinib plus BR. It is reasonable to assume that patients would be at much lower risk of COVID-19–related AEs with acalabrutinib plus BR now that vaccination and therapies for COVID-19 are widely available. If this regimen is approved, available, and reimbursed, I could see healthcare professionals considering this triplet for patients who are currently deemed appropriate for BR alone, and potentially for slightly younger patients as well.
  • An updated analysis of a phase II trial evaluating the BOVen (zanubrutinib plus obinutuzumab plus venetoclax) regimen in patients with previously untreated MCL who were ineligible for an autologous stem cell transplant (ASCT) due to age and/or comorbidities. This chemotherapy-free triplet was highly active, and patients can stop treatment after 24 cycles—approximately 2 years—if they have a complete response (CR) and undetectable measurable residual disease. I anticipate the BOVen regimen being developed further in MCL due to these advantages.

Notable clinical trial results in relapsed/refractory (R/R) MCL include:

  • A subgroup analysis of patients with TP53-mutated MCL treated with ibrutinib plus venetoclax in the phase III SYMPATICO trial. This was an interesting analysis, primarily because we lack large datasets of patients with TP53-mutated MCL. Although the median PFS with ibrutinib plus venetoclax was superior to what we see with ibrutinib alone in R/R disease, those with previously untreated disease had relatively modest benefits, suggesting that TP53 mutation is a very important driver of early disease progression. For a patient with previously untreated TP53-mutated MCL, I would currently consider a clinical trial such as OASIS-II (NCT04802590), which is evaluating a chemotherapy-free triplet of ibrutinib, venetoclax, and an anti-CD20 antibody.
  • An updated analysis of a phase I/II trial evaluating fixed-duration treatment with glofitamab, a CD3 x CD20 bispecific antibody, in patients with R/R MCL. These were intriguing data suggesting that glofitamab is highly active in heavily pretreated MCL and that a single dose of obinutuzumab pretreatment mitigates some risk of cytokine-release syndrome. The ongoing phase III GLOBRYTE trial is comparing glofitamab vs investigator’s choice of BR or lenalidomide/rituximab in patients with R/R MCL who had received 1 or more prior systemic therapy—which must include a BTK inhibitor—but had not received CAR T-cell therapy (NCT06084936).

Notable epidemiologic studies in MCL include:

  • The MCL Biobank observational study prospectively analyzed outcomes in UK patients newly diagnosed with MCL deemed eligible for watchful waiting vs immediate treatment. The most important implication is that we now have a clinical database and tissue biobank enabling better characterization and identification of patients with indolent MCL who can be safely observed. This analysis also found that approximately half of patients assigned to watchful waiting did not need treatment for 2 years—suggesting that observation is a very reasonable approach in these patients.
  • An analysis of outcomes and characteristics in a Swedish registry of patients aged 80 years or older at MCL diagnosis. The survival outcomes in this group were very poor, and clearly we must do better in treating older patients with MCL. This is a patient group that could potentially benefit from novel, well-tolerated, chemotherapy-free approaches, such as combining a covalent BTK inhibitor with an anti-CD20 antibody.

Your Thoughts?
Which of these studies do you think is the most exciting? Please answer the polling question and join the conversation by posting a comment in the discussion section.

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