Mantle Cell Lymphoma – Cutting‑ edge Diagnostics and Treatment Approaches

Česká verzia

Authors: P. Klener Jr.; M. Trněný
Authors place of work: I. interní klinika – klinika hematologie 1. LF UK a VFN v Praze
Published in the journal: Klin Onkol 2015; 28(Supplementum 3): 80-86
doi: https://doi.org/10.14735/amko20153S80

Summary

Background:
Mantle cell lymphoma represents a specific subtype of B‑ cell non‑Hodgkin lymphoma characterized on the molecular level by translocation t(11;14)(q13;q32) leading to aberrant overexpression of cyclin D₁ and deregulation of the cell cycle. Despite sporadic indolent forms of mantle cell lymphoma, majority of patients present with advanced aggressive disease that requires immediate treatment. Despite chemosensitive nature of mantle cell lymphoma, approximately 10% patients present with a refractory disease, and the vast majority of patients who initially respond to therapy, relapse sooner or later. The course of mantle cell lymphoma thus represents a chronically relapsing malignancy requiring further and further lines of therapies. Prognosis of relapsed or refractory (R/ R) mantle cell lymphoma is dismal.

Aim:
The goal of this article is to provide a cutting‑ edge review of currently used diagnostic and treatment approaches for mantle cell lymphoma.

Results:
Several key modifications of the therapeutic algorithm of mantle cell lymphoma treatment implemented in the past 10 years resulted in significantly improved prognosis of patients. The milestones in the therapy of mantle cell lymphoma include incorporation of anti‑CD20 monoclonal antibody rituximab into induction therapy, intensification of polychemotherapeutic regimen including implementation of high‑dose cytarabine, consolidation of response with high‑dose therapy and autologous stem cell transplantation (HDT‑ ASCT) in younger fit patients, and maintenance therapy with rituximab in the elderly patients. Besides such “optimization” of front‑line therapy, introduction of novel anti‑lymphoma agents into therapy of R/ R mantle cell lymphoma also contributed (and will contribute in the future) to improved prognosis of mantle cell lymphoma. Among these agents, there is a new cytostatic drug bendamustine, Bruton tyrosine‑ kinase inhibitor ibrutinib, immunomodulatory agent lenalidomide, mTOR inhibitor temsirolimus and proteasome inhibitor bortezomib.

Conclusion:
The overall survival of mantle cell lymphoma virtually doubled in the recent 10 years as a result of two key factors: 1. optimization of front‑line therapy with “conventional” anti‑lymphoma agents, and 2. brand new possibilities of therapy for R/ R mantle cell lymphoma thanks to the introduction of novel anti‑lymphoma agents. Combinatorial approaches using most efficacious combinations of novel and conventional anti‑mantle cell lymphoma agents will definitely lead to further improvements of survival parameters in mantle cell lymphoma patients in near future.

Key words:
mantle cell lymphoma – minimal residual disease – autologous transplantation

This study was supported by project PRVOUK-27//LF1/1, IGA-MZ NT/13072-4, IGA-MZ NT 13201-4/2012.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
24. 9. 2015

Accepted:
27. 9. 2015

Zdroje

1. Dreyling M. Mantle cell lymphoma: biology, clinical presentation, and therapeutic approaches. Am Soc Clin Oncol Educ Book 2014: 191– 198. doi: 10.14694/ EdBook_AM.2014.34.191.

2. Zhang J, Jima D, Moffitt AB et al. The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells. Blood 2014; 123(19): 2988– 2996. doi: 10.1182/ blood‑ 2013‑ 07‑ 517177.

3. Hoster E, Dreyling M, Klapper W et al. A new prognostic index (MIPI) for patients with advanced‑stage mantle cell lymphoma. Blood 2008; 111(2): 558– 565.

4. Hoster E, Klapper W, Hermine O et al. Confirmation of the mantle‑ cell lymphoma International Prognostic Index in randomized trials of the European Mantle‑ Cell Lymphoma Network. J Clin Oncol 2014; 32(13): 1338– 1346. doi: 10.1200/ JCO.2013.52.2466.

5. Salek D, Vesela P, Boudova L et al. Retrospective analysis of 235 unselected patients with mantle cell lymphoma confirms prognostic relevance of Mantle Cell Lymphoma International Prognostic Index and Ki‑ 67 in the era of rituximab: long‑term data from the Czech Lymphoma Project Database. Leuk Lymphoma 2014; 55(4): 802– 810. doi: 10.3109/ 10428194.2013.815349.

6. Klapper W, Hoster E, Determann O et al. Ki‑ 67 as a prognostic marker in mantle cell lymphoma‑ consensus guidelines of the pathology panel of the European MCL Network. J Hematop 2009; 2(2): 103– 111. doi: 10.1007/ s12308‑ 009‑ 0036‑ x.

7. Stefancikova L, Moulis M, Fabian P et al. Loss of the p53 tumor suppressor activity is associated with negative prognosis of mantle cell lymphoma. Int J Oncol 2010; 36(3): 699– 706.

8. Pott C, Hoster E, Delfau‑ Larue MH et al. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood 2010; 115(16): 3215– 3223. doi: 10.1182/ blood‑ 2009‑ 06‑ 230250.

9. van Dongen JJ, Langerak AW, Bruggemann M et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T‑ cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED‑ 2 Concerted Action BMH4-CT98- 3936. Leukemia 2003; 17(12): 2257– 2317.

10. Rogers YH, Venter JC. Genomics: massively parallel sequencing. Nature 2005; 437(7057): 326– 327.

11. Kalinova M, Fronkova E, Klener P et al. The use of formalin‑fixed, paraffin‑embedded lymph node samples for the detection of minimal residual disease in mantle cell lymphoma. Br J Haematol 2015; 169(1): 145– 148. doi: 10.1111/ bjh.13182.

12. Dreyling M, Ferrero S, Hermine O. How to manage mantle cell lymphoma. Leukemia 2014; 28(11): 2117– 2130. doi: 10.1038/ leu.2014.171.

13. Merli F, Luminari S, Ilariucci F et al. Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano Studio Linfomi. Br J Haematol 2012; 156(3): 346– 353. doi: 10.1111/ j.1365‑ 2141.2011.08958.x.

14. 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(2): 200– 208. doi: 10.1111/ j.1365‑ 2141.2010.08228.x.

15. 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(6): 1587– 1593. doi: 10.1093/ annonc/ mdt070.

16. Lefrere F, Delmer A, Suzan F et al. Sequential chemotherapy by CHOP and DHAP regimens followed by high‑dose therapy with stem cell transplantation induces a high rate of complete response and improves event‑free survival in mantle cell lymphoma: a prospective study. Leukemia 2002; 16(4): 587– 593.

17. 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(1): 48– 53. doi: 10.1182/ blood‑ 2011‑ 09‑ 370320.

18. 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(9): 1984– 1992.

19. 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(3): 355– 362. doi: 10.1111/ j.1365‑ 2141.2012.09174.x.

20. Robinson S, Dreger P, Caballero D et al. The EBMT/ EMCL consensus project on the role of autologous and allogeneic stem cell transplantation in mantle cell lymphoma. Leukemia 2015; 29(2): 464– 473. doi: 10.1038/ leu.2014.223.

21. Vaughn JE, Sorror ML, Storer BE et al. Long‑term sustained disease control in patients with mantle cell lymphoma with or without active disease after treatment with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Cancer. In press 2015. doi: 10.1002/ cncr.29498.

22. 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(9873): 1203– 1210. doi: 10.1016/ S0140‑ 6736(12)61763‑ 2.

23. Kluin‑Nelemans HC, Hoster E, Hermine O et al. Treatment of older patients with mantle‑ cell lymphoma. N Engl J Med 2012; 367(6): 520– 531. doi: 10.1056/ NEJMoa1200920.

24. Dreyling M, Geisler C, Hermine O et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow‑up. Ann Oncol 2014; 25 (Suppl 3): 83– 92. doi: 10.1093/ annonc/ mdu264.

25. Hess G, Herbrecht R, Romaguera J et al. Phase III study to evaluate temsirolimus compared with investigator‘s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009; 27(23): 3822– 3829.

26. Robak T. Bortezomib in the treatment of mantle cell lymphoma. Future Oncol. In press 2015.

27. 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(29): 3688– 3695. doi: 10.1200/ JCO.2013.49.2835.

28. Zinzani PL, Vose JM, Czuczman MS et al. Long‑term follow‑up of lenalidomide in relapsed/ refractory mantle cell lymphoma: subset analysis of the NHL‑003 study. Ann Oncol 2013; 24(11): 2892– 2897. doi: 10.1093/ annonc/ mdt366.

29. Robinson KS, Williams ME, van der Jagt RH et al. Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B‑ cell and mantle cell non‑Hodgkin‘s lymphoma. J Clin Oncol 2008; 26(27): 4473– 4479. 10.1200/ JCO.2008.17.0001.

30. 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(6): 507– 516. doi: 10.1056/ NEJMoa1306220.

31. 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; 31(11): 1442– 1449. doi: 10.1200/ JCO.2012.45.9842.

32. 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(7): 716– 723. doi: 10.1016/ S1470‑ 2045(12)70200‑ 0.

33. Hess G, Keller U, Scholz CW et al. Safety and efficacy of temsirolimus in combination with bendamustine and rituximab in relapsed mantle cell and follicular lymphoma. Leukemia 2015; 29(8): 1695– 1701. doi: 10.1038/leu.2015.60.