Case-Based Review

Mantle Cell Lymphoma

Hospital Physician: Hematology/Oncology. 2017 March;12(2):2-14

References

Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol 1998;16:2780–95.
Zhou Y, Wang H, Fang W, et al. Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer 2008;113:791–8.
Geisler CH. Front-line treatment of mantle cell lymphoma. Haematologica 2010;95:1241–3.
Fernandez V, Salamero O, Espinet B, et al. Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res 2010;70:1408–18.
Martin P, Chadburn A, Christos P, et al. Outcome of deferred initial therapy in mantle-cell lymphoma. J Clin Oncol 2009;27:1209–13.
Bertoni F, Ponzoni M. The cellular origin of mantle cell lymphoma. Int J Biochem Cell Biol 2007;39:1747–53.
de Boer CJ, van Krieken JH, Kluin-Nelemans HC, et al. Cyclin D1 messenger RNA overexpression as a marker for mantle cell lymphoma. Oncogene 1995;10:1833–40.
Jares P, Colomer D, Campo E. Molecular pathogenesis of mantle cell lymphoma. J Clin Invest 2012;122:3416–23.
Rosenwald A, Wright G, Wiestner A, et al. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell 2003;3:185–97.
Determann O, Hoster E, Ott G, et al. Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group. Blood 2008;111:2385–7.
Vegliante MC, Palomero J, Perez-Galan P, et al. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma. Blood 2013;121:2175–85.
Bea S, Valdes-Mas R, Navarro A, et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci U S A 2013;110:18250–5.
Zelenetz AD, Abramson JS, Advani RH, et al. Non- Hodgkin’s lymphomas. J Natl Compr Canc Netw 2011;9: 484–560.
Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32:3059–68.
Zelenetz AD, Abramson JS, Advani RH, et al. NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin’s lymphomas. J Natl Compr Canc Netw 2010;8:288–334.
Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 2008;111:558–65.
Geisler CH, Kolstad A, Laurell A, et al. The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT). Blood 2010;115:1530–3.
Tiemann M, Schrader C, Klapper W, et al. Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network. Br J Haematol 2005;131:29–38.
Raty R, Franssila K, Joensuu H, et al. Ki-67 expression level, histological subtype, and the International Prognostic Index as outcome predictors in mantle cell lymphoma. Eur J Haematol 2002;69:11–20.
Vogt N, Klapper W. Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression. Histopathology 2013;62:334–42.
Geisler CH, Kolstad A, Laurell A, et al. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood 2008;112:2687–93.
Howard OM, Gribben JG, Neuberg DS, et al. Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival. J Clin Oncol 2002;20:1288–94.
Griffiths R, Mikhael J, Gleeson M, et al. Addition of rituximab to chemotherapy alone as first-line therapy improves overall survival in elderly patients with mantle cell lymphoma. Blood 2011;118:4808–16.
Lenz G, Dreyling M, Hoster E, et al. immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 2005;23:1984–92.
Romaguera JE, Fayad L, Rodriguez MA, et al. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol 2005;23:7013–23.
Kluin-Nelemans HC, Hoster E, Hermine O, et al. Treatment of older patients with mantle-cell lymphoma. N Engl J Med 2012;367:520–31.
Robak T, Huang H, Jin J, et al. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med 2015;372:944–53.
Flinn IW, van der Jagt R, Kahl BS, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood 2014;123:2944–52.
Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 2013;381:1203–10.
Houot R, Le Gouill S, Ojeda Uribe M, et al. Combination of rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil (RiPAD+C) as first-line therapy for elderly mantle cell lymphoma patients: results of a phase II trial from the GOELAMS. Ann Oncol 2012;23:1555–61.
Ruan J, Martin P, Furman RR, et al. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol 2011;29:690–7.
Chang JE, Li H, Smith MR, et al. Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405). Blood 2014; 123:1665–73.
Romaguera JE, Fayad LE, Feng L, et al. Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. Br J Haematol 2010;150:200–8.
Bernstein SH, Epner E, Unger JM, et al. A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Ann Oncol 2013;24:1587–93.
LaCasce AS, Vandergrift JL, Rodriguez MA, et al. Comparative outcome of initial therapy for younger patients with mantle cell lymphoma: an analysis from the NCCN NHL Database. Blood 2012;119:2093–9.
Geisler CH, Kolstad A, Laurell A, et al. Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur. Br J Haematol 2012;158:355–62.
Damon LE, Johnson JL, Niedzwiecki D, et al. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol 2009;27:6101–8.
van ‘t Veer MB, de Jong D, MacKenzie M, et al. High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol 2009;144:524–30.
Delarue R, Haioun C, Ribrag V, et al. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d’Etude des Lymphomes de l’Adulte. Blood 2013;121:48–53.
Hermine O, Hoster E, Walewski J, et al. Alternating courses of 3x CHOP and 3x DHAP plus rituximab followed by a high dose ARA-C containing myeloablative regimen and autologous stem cell transplantation (ASCT) increases overall survival when compared to 6 courses of CHOP plus rituximab followed by myeloablative radiochemotherapy and ASCT in mantle cell lymphoma: final analysis of the MCL Younger Trial of the European Mantle Cell Lymphoma Network (MCL net). In: American Society of Hematology Proceedings. December 8–11, 2012; Atlanta, GA. Abstract 151.
Rummel MJ, Al-Batran SE, Kim SZ, et al. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin’s lymphoma. J Clin Oncol 2005;23:3383–9.
Pham LV, Tamayo AT, Yoshimura LC, et al. Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J Immunol 2003;171:88–95.
Fisher RI, Bernstein SH, Kahl BS, et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 2006;24:4867–74.
Friedberg JW, Vose JM, Kelly JL, et al. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood 2011;117:2807–12.
Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer 2004;4:314–22.
Qian Z, Zhang L, Cai Z, et al. Lenalidomide synergizes with dexamethasone to induce growth arrest and apoptosis of mantle cell lymphoma cells in vitro and in vivo. Leuk Res 2011;35:380–6.
Goy A, Sinha R, Williams ME, et al. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol 2013;31:3688–95.
Wang M, Fayad L, Wagner-Bartak N, et al. Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Lancet Oncol 2012;13:716–23.
Buggy JJ, Elias L. Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Int Rev Immunol 2012;31: 119–32.
Rinaldi A, Kwee I, Taborelli M, et al. Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma. Br J Haematol 2006;132:303–16.
Advani RH, Buggy JJ, Sharman JP, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 2013; 31:88–94.
Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013;369:507–16.
Rudelius M, Pittaluga S, Nishizuka S, et al. Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood 2006;108: 1668–76.
Kahl BS, Spurgeon SE, Furman RR, et al. A phase 1 study of the PI3Kdelta inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL). Blood 2014;123:3398–405.
Davids MS, Seymour JF, Gerecitano JF, et al. Updated results of a phase I first in human study of the BCL-2inhibitor ABT-199 in patients with relapsed/refractory NHL. J Clin Oncol 31, 2013 (suppl; abstr 8520).
Ansell SM, Tang H, Kurtin PJ, et al. Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. Lancet Oncol 2011;12:361–8.
Witzig TE, Geyer SM, Ghobrial I, et al. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 2005;23:5347–56.
Wang M, Oki Y, Pro B, et al. Phase II study of yttrium-90-ibritumomab tiuxetan in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009;27:5213–8.
Kolstad A, Laurell A, Jerkeman M, et al. Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma. Blood 2014;123:2953–9.
Fenske TS, Zhang MJ, Carreras J, et al. Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: analysis of transplantation timing and modality. J Clin Oncol 2014;32:273–81.
Dreyling M, Lenz G, Hoster E, et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood 2005;105:2677–84.
Goy A, Younes A, McLaughlin P, et al. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin’s lymphoma. J Clin Oncol 2005;23:667–75.
Visco C, Finotto S, Zambello R, et al. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol 2013;10;31:1442–9.
Gressin R, Callanan M, Daguindau N, et al. The Ribvd regimen (Rituximab IV, Bendamustine IV, Velcade SC, Dexamethasone IV) offers a high complete response rate In elderly patients with untreated mantle cell lymphoma. Preliminary results of the Lysa trial “Lymphome Du Manteau 2010 SA.” Blood 2013;122:370.
Krishnan A, Nademanee A, Fung HC, et al. Phase II trial of a transplantation regimen of yttrium-90 ibritumomab tiuxetan and high-dose chemotherapy in patients with non-Hodgkin’s lymphoma. J Clin Oncol 2008;26:90–5.
Nademanee A, Forman S, Molina A, et al. A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkinlymphoma. Blood 2005;106:2896–902.
Shimoni A, Avivi I, Rowe JM, et al. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer 2012;118:4706–14.
Arranz R, García-Noblejas A, Grande C, et al. First-line treatment with rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab-tiuxetan in patients with mantle cell lymphoma. Results of a multicenter, phase 2 pilot trial from the GELTAMO group. Haematologica 2013;98:1563-70.

For disease staging, bone marrow biopsy and aspiration are required. Radiographic staging using computed tomography (CT) scans and/or positron emission tomography (PET) scans had traditionally followed the Ann Arbor staging system, but recently the Lugano classification has emerged, which delineates only early or advanced stage.¹⁴ Gastrointestinal evaluation of MCL with endoscopy and colonoscopy with blind biopsies has been recommended to evaluate for the presence of lymphomatous polyps, but this is not an absolute requirement.¹⁵

RISK STRATIFICATION

At diagnosis, patients should undergo risk stratification in order to understand prognosis and possibly guide treatment. In MCL, the MCL international prognostic index (MIPI) is used. The MIPI is a prognostic tool developed exclusively for patients with MCL using data from 455 patients with advanced-stage MCL treated within 3 European clinical trials.¹⁶ The MIPI classified patients into risk groups based on age, ECOG performance status, LDH level, and WBC count. Patients were categorized into low-risk (44% of patients, median OS not reached), intermediate-risk (35%, median OS 51 months), and high-risk groups (21%, median OS 29 months). This is done through a logarithmic calculation, which can be accessed through online calculators (a prototype example can be found at www.qxmd.com/calculate-online/hematology/prognosis-mantle-cell-lymphoma-mipi). Cell proliferation using the Ki-67 index was evaluated in an exploratory analysis (the biologic [“B”] MIPI), and also demonstrated strong prognostic relevance.¹⁶ Currently, treatment of MCL patients is not stratified by MIPI outside of a clinical trial, but this useful tool assists in assessing patient prognosis and has been validated for use with both conventional chemoimmunotherapy and in the setting of autologous stem cell transplant (autoSCT).^16,17 At this point in time, the MIPI score is not used to stratify treatment, although some clinical trials are incorporating the use of the MIPI score at diagnosis. Nonetheless, given its prognostic importance, the MIPI should be performed for all MCL patients undergoing staging and evaluation for treatment to establish disease risk.

As noted, the proliferative signature, represented by the Ki-67 protein, is also highly prognostic in MCL. Ki-67 is expressed in the late G1, S, G2, and M phases of the cell cycle. The Ki-67 index is defined by the hematopathologist as the percentage of lymphoma cells staining positive for Ki-67 protein, based on the number of cells per high-power field. There is significant interobserver variability in this process, which can be minimized by assessing Ki-67 quantitatively using computer software. The prognostic significance of Ki-67 at diagnosis was established in large studies of MCL patient cohorts, with survival differing by up to 3 years.^18,19 Determann et al demonstrated the utility of the proliferative index in patients with MCL treated with standard chemoimmunotherapy.¹⁰ In this study, 249 patients with advanced-stage MCL treated within randomized trials conducted by the European MCL Network were analyzed. The Ki-67 index was found to be extremely prognostic of OS, independent of other clinical risk factors, including the MIPI score. As a continuous variable, Ki-67 indices of greater than 10% correlated with poor outcomes. The Ki-67 index has also been confirmed as prognostic in relapsed MCL.²⁰ It is important to note that, as a unique feature, the Ki-67 index has remained an independent prognostic factor, even when incorporated into the “B” MIPI.

TREATMENT

CASE CONTINUED

The patient undergoes an excisional biopsy of a cervical lymph node, which demonstrates an abnormal proliferation of small-medium–sized lymphocytes with slightly irregular nuclear contours. Immunohistochemistry shows that the abnormal lymphocytes are positive for CD20 and CD5, negative for CD10 and CD23, and diffusely positive for cyclin D1, consistent with a diagnosis of MCL. The proliferative index, as measured by the Ki-67 immunostain, is 40%. A bone marrow aspirate and biopsy are then obtained, which show a clonal population of B lymphocytes expressing the same immunophenotype as the lymph node (positive for CD20 and CD5, negative for CD10 and CD23, cyclin D1 positive). A CT scan of the neck, chest, abdomen, and pelvis with contrast is obtained, along with a PET scan. These studies identify extensive hypermetabolic lymphadenopathy in the bilateral cervical chains, supraclavicular areas, mediastinum, and hilum. Mesenteric lymph nodes are also enlarged and hypermetabolic, as are retroperitoneal lymph nodes. The spleen is noted to be enlarged with multiple hypermetabolic lesions. Based on the presence of extensive lymphadenopathy as well as bone marrow involvement, the patient is diagnosed with stage IV MCL. He undergoes risk-stratification with the MIPI. His MIPI score is 6.3, high risk.

References

Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol 1998;16:2780–95.
Zhou Y, Wang H, Fang W, et al. Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer 2008;113:791–8.
Geisler CH. Front-line treatment of mantle cell lymphoma. Haematologica 2010;95:1241–3.
Fernandez V, Salamero O, Espinet B, et al. Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res 2010;70:1408–18.
Martin P, Chadburn A, Christos P, et al. Outcome of deferred initial therapy in mantle-cell lymphoma. J Clin Oncol 2009;27:1209–13.
Bertoni F, Ponzoni M. The cellular origin of mantle cell lymphoma. Int J Biochem Cell Biol 2007;39:1747–53.
de Boer CJ, van Krieken JH, Kluin-Nelemans HC, et al. Cyclin D1 messenger RNA overexpression as a marker for mantle cell lymphoma. Oncogene 1995;10:1833–40.
Jares P, Colomer D, Campo E. Molecular pathogenesis of mantle cell lymphoma. J Clin Invest 2012;122:3416–23.
Rosenwald A, Wright G, Wiestner A, et al. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell 2003;3:185–97.
Determann O, Hoster E, Ott G, et al. Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group. Blood 2008;111:2385–7.
Vegliante MC, Palomero J, Perez-Galan P, et al. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma. Blood 2013;121:2175–85.
Bea S, Valdes-Mas R, Navarro A, et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci U S A 2013;110:18250–5.
Zelenetz AD, Abramson JS, Advani RH, et al. Non- Hodgkin’s lymphomas. J Natl Compr Canc Netw 2011;9: 484–560.
Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32:3059–68.
Zelenetz AD, Abramson JS, Advani RH, et al. NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin’s lymphomas. J Natl Compr Canc Netw 2010;8:288–334.
Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 2008;111:558–65.
Geisler CH, Kolstad A, Laurell A, et al. The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT). Blood 2010;115:1530–3.
Tiemann M, Schrader C, Klapper W, et al. Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network. Br J Haematol 2005;131:29–38.
Raty R, Franssila K, Joensuu H, et al. Ki-67 expression level, histological subtype, and the International Prognostic Index as outcome predictors in mantle cell lymphoma. Eur J Haematol 2002;69:11–20.
Vogt N, Klapper W. Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression. Histopathology 2013;62:334–42.
Geisler CH, Kolstad A, Laurell A, et al. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood 2008;112:2687–93.
Howard OM, Gribben JG, Neuberg DS, et al. Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival. J Clin Oncol 2002;20:1288–94.
Griffiths R, Mikhael J, Gleeson M, et al. Addition of rituximab to chemotherapy alone as first-line therapy improves overall survival in elderly patients with mantle cell lymphoma. Blood 2011;118:4808–16.
Lenz G, Dreyling M, Hoster E, et al. immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 2005;23:1984–92.
Romaguera JE, Fayad L, Rodriguez MA, et al. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol 2005;23:7013–23.
Kluin-Nelemans HC, Hoster E, Hermine O, et al. Treatment of older patients with mantle-cell lymphoma. N Engl J Med 2012;367:520–31.
Robak T, Huang H, Jin J, et al. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med 2015;372:944–53.
Flinn IW, van der Jagt R, Kahl BS, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood 2014;123:2944–52.
Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 2013;381:1203–10.
Houot R, Le Gouill S, Ojeda Uribe M, et al. Combination of rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil (RiPAD+C) as first-line therapy for elderly mantle cell lymphoma patients: results of a phase II trial from the GOELAMS. Ann Oncol 2012;23:1555–61.
Ruan J, Martin P, Furman RR, et al. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol 2011;29:690–7.
Chang JE, Li H, Smith MR, et al. Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405). Blood 2014; 123:1665–73.
Romaguera JE, Fayad LE, Feng L, et al. Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. Br J Haematol 2010;150:200–8.
Bernstein SH, Epner E, Unger JM, et al. A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Ann Oncol 2013;24:1587–93.
LaCasce AS, Vandergrift JL, Rodriguez MA, et al. Comparative outcome of initial therapy for younger patients with mantle cell lymphoma: an analysis from the NCCN NHL Database. Blood 2012;119:2093–9.
Geisler CH, Kolstad A, Laurell A, et al. Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur. Br J Haematol 2012;158:355–62.
Damon LE, Johnson JL, Niedzwiecki D, et al. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol 2009;27:6101–8.
van ‘t Veer MB, de Jong D, MacKenzie M, et al. High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol 2009;144:524–30.
Delarue R, Haioun C, Ribrag V, et al. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d’Etude des Lymphomes de l’Adulte. Blood 2013;121:48–53.
Hermine O, Hoster E, Walewski J, et al. Alternating courses of 3x CHOP and 3x DHAP plus rituximab followed by a high dose ARA-C containing myeloablative regimen and autologous stem cell transplantation (ASCT) increases overall survival when compared to 6 courses of CHOP plus rituximab followed by myeloablative radiochemotherapy and ASCT in mantle cell lymphoma: final analysis of the MCL Younger Trial of the European Mantle Cell Lymphoma Network (MCL net). In: American Society of Hematology Proceedings. December 8–11, 2012; Atlanta, GA. Abstract 151.
Rummel MJ, Al-Batran SE, Kim SZ, et al. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin’s lymphoma. J Clin Oncol 2005;23:3383–9.
Pham LV, Tamayo AT, Yoshimura LC, et al. Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J Immunol 2003;171:88–95.
Fisher RI, Bernstein SH, Kahl BS, et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 2006;24:4867–74.
Friedberg JW, Vose JM, Kelly JL, et al. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood 2011;117:2807–12.
Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer 2004;4:314–22.
Qian Z, Zhang L, Cai Z, et al. Lenalidomide synergizes with dexamethasone to induce growth arrest and apoptosis of mantle cell lymphoma cells in vitro and in vivo. Leuk Res 2011;35:380–6.
Goy A, Sinha R, Williams ME, et al. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol 2013;31:3688–95.
Wang M, Fayad L, Wagner-Bartak N, et al. Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Lancet Oncol 2012;13:716–23.
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Mantle Cell Lymphoma

References

RISK STRATIFICATION

TREATMENT

CASE CONTINUED

Pages

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