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Review article: Biomedical intelligence

Vol. 143 No. 4546 (2013)

Diagnosis and treatment of mantle cell lymphoma

  • Felicitas Hitz
  • Mario Bargetzi
  • Sergio Cogliatti
  • Andreas Lohri
  • Christian Taverna
  • Christoph Renner
  • Ulrich Mey
DOI
https://doi.org/10.4414/smw.2013.13868
Cite this as:
Swiss Med Wkly. 2013;143:w13868
Published
03.11.2013

Summary

Mantle cell lymphoma (MCL) is a relatively rare lymphoma entity accounting for an estimated 3%–6% of all non-Hodgkin’s lymphoma cases. Characterised by both the incurability of indolent lymphomas and the rapid growth of aggressive lymphomas, MCL has a median overall survival of only 4–5 years. Although the disease often shows an encouraging response to first-line treatment, its clinical course is usually marked by recurrent relapses, resulting in a dismal long-term outcome. The choice of therapy for managing the disease is a complex problem that still requires evidence-based guidance. Owing to the rarity of MCL, the bulk of data comes from phase II trials in small numbers of patients. Nevertheless, therapeutic strategies for MCL have evolved in an effort to adapt treatment according to the individual patient’s risk profile, and the overall survival has nearly doubled in the last 30 years. The use of effective immunochemotherapy regimens in first-line therapy, advances in stem cell transplantation, and the development of more active salvage therapy regimens have improved the outcome. This review will summarise the key factors that drive clinical practice with respect to the management of MCL.

References

  1. Andersen NS, Jensen MK, de Nully BP, et al. A Danish population-based analysis of 105 mantle cell lymphoma patients: incidences, clinical features, response, survival and prognostic factors. Eur J Cancer. 2002;38:401–8.
  2. The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood. 1997;89:3909–18.
  3. Velders GA, Kluin-Nelemans JC, De Boer CJ, et al. Mantle-cell lymphoma: a population-based clinical study. J Clin Oncol. 1996;14:1269–74.
  4. Argatoff LH, Connors JM, Klasa RJ, et al. Mantle cell lymphoma: a clinicopathologic study of 80 cases. Blood. 1997;89:2067–78.
  5. Herrmann A, Hoster E, Zwingers T, et al. Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol. 2009;27:511–8.
  6. Dreyling M and Hiddemann W. Current treatment standards and emerging strategies in mantle cell lymphoma. Hematology Am Soc Hematol Educ Program. 2009;542–51.
  7. 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.
  8. 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.
  9. Schulz H, Bohlius JF, Trelle S, et al. Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2007;99:706–14.
  10. Ghielmini M, Zucca E. How I treat mantle cell lymphoma. Blood. 2009;114:1469–76.
  11. Vose JM. Mantle cell lymphoma: 2012 update on diagnosis, risk-stratification, and clinical management. Am J Hematol. 2012;87:604–9.
  12. Pileri SA, Falini B. Mantle cell lymphoma. Haematologica. 2009;94:1488–92.
  13. Romaguera JE, Medeiros LJ, Hagemeister FB, et al. Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma. Cancer. 2003;97:586–91.
  14. Salar A, Juanpere N, Bellosillo B, et al. Gastrointestinal involvement in mantle cell lymphoma: a prospective clinic, endoscopic, and pathologic study. Am J Surg Pathol. 2006;30:1274–80.
  15. Ferrer A, Bosch F, Villamor N, et al. Central nervous system involvement in mantle cell lymphoma. Ann Oncol. 2008;19:135–41.
  16. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue (IARC WHO Classification of Tumours). World Health Organization. 2008; 4th edition.
  17. Bertoni F, Ponzoni M. The cellular origin of mantle cell lymphoma. Int J Biochem Cell Biol. 2007;39:1747–53.
  18. Cogliatti SB, Bertoni F, Zimmermann DR, et al. IgV H mutations in blastoid mantle cell lymphoma characterize a subgroup with a tendency to more favourable clinical outcome. J Pathol. 2005;206:320–7.
  19. Chen YH, Gao J, Fan G, et al. Nuclear expression of sox11 is highly associated with mantle cell lymphoma but is independent of t(11;14)(q13;q32) in non-mantle cell B-cell neoplasms. Mod Pathol. 2010;23:105–12.
  20. Mozos A, Royo C, Hartmann E, et al. SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica. 2009;94:1555–62.
  21. Bertoni F, Rinaldi A, Zucca E, et al. Update on the molecular biology of mantle cell lymphoma. Hematol Oncol. 2006;24:22–7.
  22. 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.
  23. Shah BD, Martin P, Sotomayor EM. Mantle cell lymphoma: a clinically heterogeneous disease in need of tailored approaches. Cancer Control. 2012;19:227–35.
  24. Belaud-Rotureau MA, Parrens M, Dubus P, et al. A comparative analysis of FISH, RT-PCR, PCR, and immunohistochemistry for the diagnosis of mantle cell lymphomas. Mod Pathol. 2002;15:517–25.
  25. Mato AR, Svoboda J, Feldman T, et al. Post-treatment (not interim) positron emission tomography-computed tomography scan status is highly predictive of outcome in mantle cell lymphoma patients treated with R-HyperCVAD. Cancer. 2012;118:3565–70.
  26. Gill S, Herbert KE, Prince HM, et al. Mantle cell lymphoma with central nervous system involvement: frequency and clinical features. Br J Haematol. 2009;147:83–8.
  27. 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.
  28. 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.
  29. 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;2:103–11.
  30. 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.
  31. Martin P, Chadburn A, Christos P, et al. Outcome of deferred initial therapy in mantle-cell lymphoma. J Clin Oncol. 2009;27:1209–13.
  32. Martin P and Leonard J. Is there a role for “watch and wait” in patients with mantle cell lymphoma? Semin Hematol. 2011;48:189–93.
  33. Chandran R, Gardiner SK, Simon M, et al. Survival trends in mantle cell lymphoma in the United States over 16 years 1992–2007. Leuk Lymphoma. 2012;53:1488–93.
  34. Leitch HA, Gascoyne RD, Chhanabhai M, et al. Limited-stage mantle-cell lymphoma. Ann Oncol. 2003;14:1555–61.
  35. Bernard M, Tsang RW, Le LW, et al. Limited-stage mantle-cell lymphoma: Treatment outcomes at the Princess Margaret Hospital. Leuk Lymphoma. 2012; epub before print.
  36. Samaha H, Dumontet C, Ketterer N, et al. Mantle cell lymphoma: a retrospective study of 121 cases. Leukemia. 1998;12:1281–7.
  37. Vandenberghe E, De Wolf-Peeters C, Vaughan HG, et al. The clinical outcome of 65 cases of mantle cell lymphoma initially treated with non-intensive therapy by the British National Lymphoma Investigation Group. Br J Haematol. 1997;99:842–7.
  38. Dreyling M, Kluin-Nelemans HC, Bea S, et al. Update on the molecular pathogenesis and clinical treatment of mantle cell lymphoma: report of the 10th annual conference of the European Mantle Cell Lymphoma Network. Leuk Lymphoma. 2011;52:2226–36.
  39. Hoster E, Unterhalt M, Wormann B, et al. The Addition of Rituximab to First-Line Chemotherapy (R-CHOP) Results in Superior Response Rates, Time to Treatment Failure and Response Duration in Patients with Advanced Stage Mantle Cell Lymphoma: Long Term Results of a Randomized GLSG Trial. Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 3049.
  40. 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.
  41. 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.
  42. 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.
  43. 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). Blood (ASH Annual Meeting Abstracts). 2012;120:Abstract 151.
  44. 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.
  45. 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.
  46. 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.
  47. Smith MR, Li H, Gordon L, et al. Phase II Study of Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Immunochemotherapy Followed by Yttrium-90-Ibritumomab Tiuxetan in Untreated Mantle-Cell Lymphoma: Eastern Cooperative Oncology Group Study E1499. J Clin Oncol. 2012;30:3119–26.
  48. 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.
  49. 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;156:346–53.
  50. 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.
  51. Flinn IW, van der Jagt RH, Kahl BS, et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. Blood (ASH Annual Meeting Abstracts). 2012;120:Abstract 902.
  52. Burke JM, van der Jagt RH, Kahl B, et al. Differences in Quality of Life Between Bendamustine Plus Rituximab Compared with Standard First-Line Treatments in Patients with Previously Untreated Advanced Indolent Non-Hodgkin’s Lymphoma or Mantle Cell Lymphoma. Blood (ASH Annual Meeting Abstracts). 2012; 120: Abstract 155.
  53. Martin P, Smith M, and Till B. Management of mantle cell lymphoma in the elderly. Best Pract Res Clin Haematol. 2012;25:221–31.
  54. Weidmann E, Neumann A, Fauth F, et al. Phase II study of bendamustine in combination with rituximab as first-line treatment in patients 80 years or older with aggressive B-cell lymphomas. Ann Oncol. 2011;22:1839–44.
  55. Ghielmini M, Schmitz SF, Cogliatti S, et al. Effect of single-agent rituximab given at the standard schedule or as prolonged treatment in patients with mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research (SAKK). J Clin Oncol. 2005;23:705–11.
  56. Reddy N, Greer JP, Goodman S, et al. Consolidative therapy with stem cell transplantation improves survival of patients with mantle cell lymphoma after any induction regimen. Exp Hematol. 2012;40:359–66.
  57. Cassaday RD and Gopal AK. Allogeneic hematopoietic cell transplantation in mantle cell lymphoma. Best Pract Res Clin Haematol. 2012;25:165–74.
  58. Tam CS, Bassett R, Ledesma C, et al. Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood. 2009;113:4144–52.
  59. Ruan J, Coleman M, and Leonard JP. Management of relapsed mantle cell lymphoma: still a treatment challenge. Oncology (Williston Park). 2009;23:683–90.
  60. Forstpointner R, Unterhalt M, Dreyling M, et al. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006;108:4003–8.
  61. Kenkre VP, Long WL, Eickhoff JC, et al. Maintenance rituximab following induction chemo-immunotherapy for mantle cell lymphoma: long-term follow-up of a pilot study from the Wisconsin Oncology Network. Leuk Lymphoma. 2011;52:1675–80.
  62. Moosmann P, Heizmann M, Kotrubczik N, et al. Weekly treatment with a combination of bortezomib and bendamustine in relapsed or refractory indolent non-Hodgkin lymphoma. Leuk Lymphoma. 2010;51:149–52.
  63. Rigacci L, Puccini B, Cortelazzo S, et al. Bendamustine with or without rituximab for the treatment of heavily pretreated non-Hodgkin's lymphoma patients : A multicenter retrospective study on behalf of the Italian Lymphoma Foundation (FIL). Ann Hematol. 2012;91:1013–22.
  64. 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;26:4473–9.
  65. 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.
  66. Thomas DW, Owen RG, Johnson SA, et al. Superior quality and duration of responses among patients with mantle-cell lymphoma treated with fludarabine and cyclophosphamide with or without rituximab compared with prior responses to CHOP. Leuk Lymphoma. 2005;46:549–52.
  67. Forstpointner R, Dreyling M, Repp R, et al. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004;104:3064–71.
  68. 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.
  69. O’Connor OA, Wright J, Moskowitz C, et al. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2005;23:676–84.
  70. 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.
  71. 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.
  72. Lamm W, Kaufmann H, Raderer M, et al. Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma. Haematologica. 2011;96:1008–14.
  73. Kirschey S, Wagner S, and Hess G. Relapsed and/or Refractory Mantle Cell Lymphoma: What Role for Temsirolimus? Clin Med Insights Oncol. 2012;6:153–64.
  74. 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;27:3822–9.
  75. Renner C, Zinzani PL, Gressin R, et al. A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma. Haematologica. 2012;97:1085–91.
  76. Habermann TM, Lossos IS, Justice G, et al. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol. 2009;145:344–9.
  77. 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.
  78. Wang M, Rule SA, Martin P, et al. Interim Results of an International, Multicenter, Phase 2 Study of Bruton’s Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), in Relapsed or Refractory Mantle Cell Lymphoma (MCL): Durable Efficacy and Tolerability with Longer Follow-up. Blood (ASH Annual Meeting Abstracts). 2012;120:Abstract 904.
  79. Perez-Galan P, Dreyling M, Wiestner A. Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era. Blood. 2011;117:26–38.
  80. Witzig TE, Reeder CB, LaPlant BR, et al. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2011;25:341–7.
  81. Rizzieri DA, Feldman E, Dipersio JF, et al. A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2008;14:2756-2762.
  82. Houot R, Le GS, Ojeda UM, 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.
  83. Goy A, Bernstein SH, Kahl BS, et al. Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study. Ann Oncol. 2009;20:520–5.
  84. O’Connor OA, Moskowitz C, Portlock C, et al. Patients with chemotherapy-refractory mantle cell lymphoma experience high response rates and identical progression-free survivals compared with patients with relapsed disease following treatment with single agent bortezomib: results of a multicentre Phase 2 clinical trial. Br J Haematol. 2009;145:34–9.
  85. Ruschak AM, Slassi M, Kay LE, et al. Novel proteasome inhibitors to overcome bortezomib resistance. J Natl Cancer Inst. 2011;103:1007–17.
  86. O’Connor OA, Stewart AK, Vallone M, et al. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin Cancer Res. 2009;15:7085–91.
  87. Kotla V, Goel S, Nischal S, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009;2:36.
  88. Zaja F, De LS, Vitolo U, et al. Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neo-angiogenic biomarkers. Haematologica. 2012;97:416–22.
  89. Eve HE, Carey S, Richardson SJ, et al. Single-agent lenalidomide in relapsed/refractory mantle cell lymphoma: results from a UK phase II study suggest activity and possible gender differences. Br J Haematol. 2012;159:154–63.
  90. Gunnellini M, Falchi L. Therapeutic Activity of Lenalidomide in Mantle Cell Lymphoma and Indolent Non-Hodgkin’s Lymphomas. Adv Hematol. 2012; epub.
  91. Lin TS, Blum KA, Fischer DB, et al. Flavopiridol, fludarabine, and rituximab in mantle cell lymphoma and indolent B-cell lymphoproliferative disorders. J Clin Oncol. 2010;28:418–23.
  92. Lin TS, Ruppert AS, Johnson AJ, et al. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol. 2009;27:6012–8.
  93. Leonard JP, LaCasce AS, Smith MR, et al. Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma. Blood. 2012;119:4597–607.
  94. Herman SE, Gordon AL, Wagner AJ, et al. Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood. 2010;116:2078–88.
  95. Lannutti BJ, Meadows SA, Herman SE, et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011;117:591–4.
  96. Iyengar S, Clear A, Bodor C, et al. P110alpha-mediated constitutive PI3K signaling limits the efficacy of p110delta-selective inhibition in mantle cell lymphoma, particularly with multiple relapse. Blood. 2013;121:2274–84.

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