Insights about treating newly diagnosed MCL

  • ASH 2020
  • 27 Aug 2020

  • curated by Pavankumar Kamat
  • Univadis Clinical Summaries
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  • Eduardo M. Sotomayor, MD, provided insights into treating newly diagnosed mantle cell lymphoma (MCL) at a session during the recent American Society of Hematology's (ASH) Meeting on Hematological Malignancies. 

Key points

  • Although MCL traditionally has been viewed as quite aggressive with poor outcomes, recent research suggests considerable variation in outcomes.
  • Identification of biomarkers is crucial for determining which patients would do best with a watch-and-wait strategy and who will need an aggressive treatment strategy for MCL.
  • Around 10%-20% of patients with MCL have a clinically indolent lymphoma.
    • The indicative biomarkers for such cases include low or absent expression of the transcription marker SOX11 and a recently identified 16-gene signature called L-MCL16.
  • Patients with indolent disease can have a 5-year survival as high as 100% vs 49% for those with classical MCL.
  • Minimal residual disease (MRD) is a key risk stratification measure in addition to the Mantle Cell Lymphoma International Prognostic Index (MIPI) and the simplified (s)-MIPI.
  • Patients with indolent MCL typically have a leukemic, non-nodal presentation with lymphocytosis and splenomegaly, but no or minimal lymphadenopathy.
  • Sotomayor recommends a watchful waiting approach, with a close follow-up for such patients.
  • Failure of disease progression within a year of diagnosis provides some reasonable assurance about the indolent nature of MCL.
  • However, once there is progression, treatment should proceed according to the type of progression ("classical" or aggressive), says Sotomayor.
  • Although the diagnosis of MCL remains relatively straightforward, identification of patients needing treatment vs watchful waiting is the biggest challenge.
  • According to Sotomayor, multiple factors influence treatment decisions in patients with classical MCL.
  • There should be a balance of tumor characteristics with the intensity of the therapy, patient age, tolerance, and comorbid conditions, and unique features of the disease.
  • Bruton tyrosine kinase (BTK) inhibitors, B-cell lymphoma-2 (BCL-2) inhibitors, and novel immune therapies such as chimeric antigen receptor (CAR) T-cell therapy are among new treatment developments for MCL.
  • The emerging evidence about CAR T cells in MCL is particularly encouraging, says Sotomayor.
  • Brexucabtagene autoleucel (Tecartus) was granted accelerated approval by the US Food and Drug Administration in July 2020, based on the positive findings from the ZUMA-2 phase 2 multicenter trial.