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Updated ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of newly diagnosed and R/R Mantle Cell Lymphoma

Jul 26, 2017

On 13 thJuly 2017, on behalf of the European Society for Medical Oncology ( ESMO) Guidelines Committee, M. Dreylingfrom the Hospital of the Ludwig-Maximilians-University, Munich, Germany, et al. publishedupdated clinical practice guidelines for newly diagnosed and Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) in the Annals of Oncology. 1

This article highlights the key recommendations given by the ESMO Guidelines Committee in terms of diagnosis, staging, treatment, response evaluation, and follow-up.

Diagnosis and pathology/molecular biology

  • Surgical specimens, preferably lymph node biopsy, should be used for diagnosis
  • Core biopsies should only be undertaken in patients without easily accessible lymph nodes
  • Bone Marrow (BM) biopsy may be relevant only in rare patients with leukemic manifestations
  • Besides histomorphology, additional diagnostic measures include immunophenotype (CD5+, CD19/20+), presence of t(11;14)(q13;q32), and cyclin D1 overexpression
  • The histological report should state the diagnosis in accordance with the WHO classification; Ki67 is the most established histomorphological risk factor
  • Most cases display classic morphology of small-median sized cells containing irregular nuclei
  • Few cases of leukemic non-nodal subtype are diagnosed correctly based on histology alone, therefore review by an expert hematopathologist is advised and additional immunohistochemical detection of cyclin D1 overexpression is mandatory
  • Identification of SOX11 may assist in making a diagnosis in rare cyclin D1-negative cases

Staging and risk assessment

  • Initial work-up: CT scan of neck, thorax, abdomen, and pelvis, and BM aspirate and biopsy
  • PET-CT is recommended for patients with rare limited stages I/II before localized radiotherapy
  • In these rare cases, gastrointestinal endoscopy is recommended to detect asymptomatic involvement but otherwise is only required in symptomatic patients; most patients will have gastrointestinal involvement
  • A lumbar puncture to detect CNS involvement may be considered in high-risk cases that have 2 or more of the following risk factors: blastoid variant, elevated LDH, impaired performance status, or neurological symptoms
  • Also required is full blood count, bloody chemistry (LDH and uric acid), and screening for HIV, Hepatitis B, and Hepatitis C viruses
  • The Lugano classification system is referred to for staging; it is important to mention bulky disease >5cm as appropriate
  • Evaluation of Ki67 has been found to vary between pathologists in terms of reproducibility; a standardized method has been proposed 2
  • A combined MCL International Prognostic Index (MIPI-c) has been established (web-based calculator: and should be applied in routine practice to estimate the clinical behavior
  • No markers have thus far been defined to predict indolent disease course


  • Indolent: Short period of ‘watch and wait’ under close observation; if therapy is needed then the recommendations for classical MCL apply
  • Localized stages (I–II): discuss conventional chemotherapy followed by radiotherapy (30–36 Gy)
  • Advanced stages (III–IV):
    • Younger patients (≤65 years): high dose-AraC containing regimens plus rituximab followed by Autologous Stem Cell Transplant (ASCT) and rituximab maintenance
    • Elderly patients (>65 years): conventional immunochemotherapy (e.g. R-CHOP, VR-CAP, BR, R-BAC) followed by rituximab maintenance
  • Relapse:
    • Targeted approaches (ibrutinib, lenalidomide) should be considered; temsirolimus and bortezomib should be considered preferably combined with chemotherapy
    • For younger patients, an Allogeneic Stem Cell Transplant (allo-SCT) should be considered
    • Consider enrollment in clinical trials

Response evaluation

  • PET-CT according to the Lugano classification system is optional
  • Radiological tests should be undertaken mid- and post-chemotherapy
  • Assessment of Minimal Residual Disease (MRD) is advised for clinical trials but not in routine practice, except in the setting of donor lymphocyte infusion post-allograft
Table 1. Follow-up



Year 1–2

Year 3–5

Year >5


B symptoms

Every 3 months

Twice annually


Physical examination

Peripheral lymph nodes, liver, spleen

Every 3 months

Twice annually


Laboratory work-up

Blood and differential count; LDH

Every 3 months

Twice annually



Abdominal ultrasound;

CT neck, chest, abdomen, pelvis

Optional: every 3–6 months

Optional: every 3–6 months

If progress suspected


Thyroid-stimulating hormone if irradiated




Personalized medicine

  • Currently, more research is required to determine molecular markers that could potentially become targets for more personalized approaches
  • Novel agents, in particular those that target the BCR pathway, BCL-2, or cyclin dependent kinases, are presently being explored

  1. Dreyling M. et al.Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology.2017 Jul 13; 28(supplement 4):iv62–iv71. DOI:10.1093/annonc/mdx223.
  2. Klapper W. et al.Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network. Journal of Hematopathology. 2009 Jul; 2(2):103–11. DOI:10.1007/s12308-009-0036-x. [Epub 2009 Jun 16].