Guideline sources The following summarized guidelines for the evaluation and management of mantle cell lymphoma (MIPI) are prepared by our editorial team based on guidelines from the American Society for Clinical Pathology (ASCP/CAP 2021), the American Society of Blood and Marrow Transplantation (ASBMT/EBMT/CIBMTR 2019), the British Society for Haematology (BSH 2018), and the European Society of Medical Oncology (ESMO 2018; 2017). 1 2 3 4 5 Calculator Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s Modified A Guidelines 1. Classification and risk stratification https://web.pathway.md/diseases/rechtaWT9MJ5INwHA 1/6 6/30/23, 1:00 AM Mantle cell lymphoma Pathway Prognostic scores: use clinical and biological prognostic scores (such as the combined Mantle Cell Lymphoma International Prognostic Index) in clinical routine to estimate the clinical behavior. E 2. Diagnostic procedures Biopsy: perform excisional or core needle biopsy in patients with high suspicion of lymphoma. A Show 3 more Fine needle aspiration: Do not obtain FNA cytomorphology alone without ancillary testing to achieve a definitive diagnosis of lymphoma. D Consider obtaining FISH analysis on specimens obtained by FNA to increase diagnostic yield. C Ancillary testing: As per ASCP 2021 guidelines, obtain immunophenotyping by flow cytometry and/or immunohistochemistry in addition to morphology for the evaluation of specimens for the diagnosis and subclassification of lymphomas. A Show 3 more As per ESMO 2017 guidelines, obtain histomorphological assessment by an expert hematopathologist, immunophenotyping (CD5+, CD19/20+), Ki-67 staining, and mandatory detection of cyclin D1 overexpression or t(11;14)(q13;q32) translocation. E Lumbar puncture: consider obtaining examination of CSF for the evaluation of primary or secondary CNS lymphoma in selected patients. C Show 2 more 3. Medical management General principles: Take into account the following when deciding on the treatment of patients with MIPI: clinical presentation (with recognition of the indolent form) proliferation index clinical risk scores (such as the simplified Mantle Cell Lymphoma International Prognostic Index and combined Mantle Cell Lymphoma International Prognostic Index) performance status. B Induction therapy: As per BSH 2018 guidelines, consider offering a period of observation before initiating definitive therapy in patients presenting with indolent disease. C Show 5 more https://web.pathway.md/diseases/rechtaWT9MJ5INwHA 2/6 6/30/23, 1:00 AM Mantle cell lymphoma Pathway Landmark trials: StiL In patients with advanced indolent and mantle cell lymphomas, bendamustine plus rituximab was superior to R-CHOP with respect to median progression-free survival. Rummel MJ et al. Lancet. 2013 Apr 6. As per ESMO 2017 guidelines, offer conventional chemotherapy followed by radiotherapy (30- 36 Gy) in patients with localized MIPI. E Show 2 more Maintenance therapy: As per ASBMT 2019 guidelines, offer maintenance therapy with rituximab every 2 months for 3 years for upfront ASCT in patients with chemosensitive MIPI after one line of prior rituximab and cytarabine-containing therapy. A Show 8 more As per BSH 2018 guidelines: Offer maintenance rituximab therapy in patients achieving treatment response (complete or partial) following rituximab-containing chemotherapy and not proceeding to ASCT. B Offer maintenance rituximab after ASCT in fit patients treated with intensive induction. A As per ESMO 2017 guidelines: Offer rituximab maintenance after high-dose cytarabine-containing regimens plus rituximab in younger patients with advanced MIPI. E Offer rituximab maintenance after conventional immunochemotherapy in elderly patients with advanced MIPI. E 4. Therapeutic procedures Stem cell transplantation: As per BSH 2018 guidelines, consider offering ASCT as first-line consolidation therapy in all patients deemed fit for intensive therapy. Obtain a thorough assessment for the suitability of this approach in > 60 years old patients. B Show 5 more As per ESMO 2017 guidelines: Offer ASCT after high-dose cytarabine-containing regimens plus rituximab in younger patients with advanced MIPI. E Consider offering allo-SCT in younger patients with relapse. E 5. Specific circumstances Elderly patients (geriatric assessment): https://web.pathway.md/diseases/rechtaWT9MJ5INwHA 3/6 6/30/23, 1:00 AM Mantle cell lymphoma Pathway Obtain a geriatric assessment in the diagnostic process of clinical trials in order to assess patient fitness. B Consider obtaining a geriatric assessment in the diagnostic process to assess patient fitness in routine clinical practice. Consider obtaining geriatric screening (such as the G8 tool) if a geriatric assessment is not possible. C Elderly patients (quality of life assessment): consider assessing the quality of life as a prognostic indicator of survival. B Show 2 more Elderly patients (diagnostic work-up): obtain diagnostic work-up in elderly patients generally not differing from patients of a younger age. B Show 3 more Elderly patients, chemoimmunotherapy: As per ESMO 2018 guidelines, offer the following chemoimmunotherapeutic regimens as the preferred first-line treatment options in elderly fit patients with MIPI: Situation Guidance Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone, followed by rituximab maintenance A R-CHOP Rituximab and bendamustine A BR Bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone A VR-CAP Rituximab, bendamustine, and cytarabine. B R-BAC Show 5 more As per ESMO 2017 guidelines, offer conventional chemimmunotherapy (such as R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; VR-CAP: bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone; BR: rituximab and bendamustine, R-BAC: rituximab, bendamustine, and cytarabine) as induction therapy followed by rituximab maintenance in elderly patients with advanced MIPI. E Elderly patients (stem cell transplantation): obtain a thorough assessment for the suitability of ASCT as first-line consolidation therapy in > 60 years old patients. A 6. Follow-up and surveillance Assessment of treatment response: Obtain conventional CT for the assessment of treatment response. B https://web.pathway.md/diseases/rechtaWT9MJ5INwHA 4/6 6/30/23, 1:00 AM Mantle cell lymphoma Pathway Do not obtain 18F-FDG-positron emission tomography or evaluation of minimal residual disease status for the assessment of treatment response outside a clinical trial. D Management of relapse: As per BSH 2018 guidelines, adopt an individualized approach based on age, comorbidities, performance status, and response and toxicity with prior therapy for the treatment of patients with relapse. B Show 6 more As per ESMO 2017 guidelines, consider offering targeted approaches (ibrutinib, lenalidomide) in patients with relapse. Combine temsirolimus and bortezomib with chemotherapy. E Show 2 more Clinical findings Patient demographics Symptoms Elderly age Abdominal discomfort Bloating Past medical history Confusion Early satiety Tumor lysis syndrome Fatigue Ocular exam Fever Headache Lacrimal gland enlargement Night sweats Weight loss Lymphatic exam Neurological exam Axillary lymphadenopathy Cervical lymphadenopathy Altered mental status Inguinal lymphadenopathy Lymphadenopathy Abdominal exam Supraclavicular lymphadenopathy Abdominal distension Splenomegaly Lab findings Integument exam serum LDH Skin nodules serum -2 microglobulin Skin papules Genetic testing Skin plaques Sox11 gene mutation Hematological findings T(11;14)(q13;q32) translocation Anemia Pancytopenia WBC count blood leukocyte count https://web.pathway.md/diseases/rechtaWT9MJ5INwHA 5/6 6/30/23, 1:00 AM Mantle cell lymphoma Pathway blood platelet count Histological findings Cyclin B1 overexpression Sox11 overexpression Studies 2020 TRIST In patients with hematologic malignancies requiring hematopoietic cell transplantation, restrictive strategy was noninferior to liberal strategy with respect to a health-related quality of life measured by Functional Assessment of Cancer Therapy-BMT score at day 100. Jason Tay et al. J Clin Oncol. 2020 May 1. 2013 StiL In patients with advanced indolent and mantle cell lymphomas, bendamustine plus rituximab was superior to R-CHOP with respect to median progression-free survival. Rummel MJ et al. Lancet. 2013 Apr 6. References 1. Steven H Kroft, Cordelia E Sever, Adam Bagg et al. Laboratory Workup of Lymphoma in Adults: Guideline From the American Society for Clinical Pathology and the College of American Pathologists. Arch Pathol Lab Med. 2021 Mar 1;145 3 269 290. Open 2. M Dreyling, E Campo, O Hermine et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv62- iv71. Open 3. Abraham S Kanate, Ambuj Kumar, Peter Dreger et al. Maintenance Therapies for Hodgkin and Non- Hodgkin Lymphomas After Autologous Transplantation: A Consensus Project of ASBMT, CIBMTR, and the Lymphoma Working Party of EBMT. JAMA Oncol. 2019 May 1;5 5 715 722. Open 4. Pamela McKay, Mike Leach, Bob Jackson et al. Guideline for the management of mantle cell lymphoma. Br J Haematol. 2018 Jul;182 1 46 62. Open 5. C Buske, M Hutchings, M Ladetto et al. ESMO Consensus Conference on malignant lymphoma: general perspectives and recommendations for the clinical management of the elderly patient with malignant lymphoma. Ann Oncol. 2018 Mar 1;29 3 544 562. Open 6. M Hutchings, M Ladetto, C Buske et al. ESMO Consensus Conference on malignant lymphoma: management of 'ultra-high-risk' patients. Ann Oncol. 2018 Aug 1;29 8 1687 1700. Open https://web.pathway.md/diseases/rechtaWT9MJ5INwHA 6/6