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Erschienen in: memo - Magazine of European Medical Oncology 3/2015

01.09.2015 | short review

Changing treatment paradigms in lymphoma: new targets and new drugs

verfasst von: MD Michael Mian, MD Annalisa Chiappella

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 3/2015

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Abstract

The knowledge about biological mechanisms contributing to lymphomagenesis represents the basis for targeted therapies in lymphoproliferative disorders. Herein, we provide a short overview about the novel drugs targeting B-cell non-Hodgkin lymphomas, with a focus on diffuse large B-cell lymphomas. Due to the plethora of new drugs, we present some of the most important new drug developments in lymphoma treatment, namely humanized monoclonal antibodies, monoclonal antibody conjugates, immunomodulatory agents, and tyrosine kinase inhibitors. The use of these agents alone or in combination with chemotherapy showed promising results with a good safety profile in a setting of relapsed/refractory lymphomas. Since many of them demonstrated to be highly active, several clinical trials evaluating their efficacy in first-line treatment are ongoing.
Literatur
1.
Zurück zum Zitat Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. N Engl J Med. 2002;346:235242. CrossRef Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. N Engl J Med. 2002;346:235242. CrossRef
2.
Zurück zum Zitat Niederfellner G, Lammens A, Mundigl O, et al. Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies. Blood. 2011;118:358–67. CrossRefPubMed Niederfellner G, Lammens A, Mundigl O, et al. Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies. Blood. 2011;118:358–67. CrossRefPubMed
3.
Zurück zum Zitat Mössner E, Brünker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010;115(22):4393–402. PubMedCentralCrossRefPubMed Mössner E, Brünker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010;115(22):4393–402. PubMedCentralCrossRefPubMed
4.
Zurück zum Zitat Salles G, Morschhauser F, Lamy T, et al. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012;119(22):5126–32. CrossRefPubMed Salles G, Morschhauser F, Lamy T, et al. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012;119(22):5126–32. CrossRefPubMed
5.
Zurück zum Zitat Morschhauser FA, Cartron G, Thieblemont C, et al. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013;31(23):2912–9. CrossRefPubMed Morschhauser FA, Cartron G, Thieblemont C, et al. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013;31(23):2912–9. CrossRefPubMed
6.
Zurück zum Zitat Robak T, Robak E. Current phase II antibody-drug conjugates for the treatment of lymphoid malignancies. Expert Opin Investig Drugs. 2014;23(7):911–24. CrossRefPubMed Robak T, Robak E. Current phase II antibody-drug conjugates for the treatment of lymphoid malignancies. Expert Opin Investig Drugs. 2014;23(7):911–24. CrossRefPubMed
7.
Zurück zum Zitat Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363:1812–21. CrossRefPubMed Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363:1812–21. CrossRefPubMed
8.
Zurück zum Zitat Pfeifer M, Zheng B, Erdmann T, et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 2015. [Epub ahead of print]. Pfeifer M, Zheng B, Erdmann T, et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 2015. [Epub ahead of print].
9.
Zurück zum Zitat Palanca-Wessels MC, Czuczman M, Salles G, et al. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet Oncol 2015. [Epub ahead of print]. Palanca-Wessels MC, Czuczman M, Salles G, et al. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet Oncol 2015. [Epub ahead of print].
10.
Zurück zum Zitat Lentzsch S, LeBlanc R, Podar K, et al. Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Leukemia. 2003;17:41–4. CrossRefPubMed Lentzsch S, LeBlanc R, Podar K, et al. Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Leukemia. 2003;17:41–4. CrossRefPubMed
11.
Zurück zum Zitat Wu L, Adams M, Carter T, et al. Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20 + tumor cells. Clin Cancer Res. 2008;14:4650–7. CrossRefPubMed Wu L, Adams M, Carter T, et al. Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20 + tumor cells. Clin Cancer Res. 2008;14:4650–7. CrossRefPubMed
12.
Zurück zum Zitat Zhang LH, Kosek J, Wang M, et al. Lenalidomide efficacy in activated B-cell-like subtype diffuse large B-cell lymphoma is dependent upon IRF4 and cereblon expression. Br J Haematol. 2013;160:487–502. CrossRefPubMed Zhang LH, Kosek J, Wang M, et al. Lenalidomide efficacy in activated B-cell-like subtype diffuse large B-cell lymphoma is dependent upon IRF4 and cereblon expression. Br J Haematol. 2013;160:487–502. CrossRefPubMed
13.
Zurück zum Zitat Yang Y, Shaffer AL 3rd, Emre NC, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21:723–37. PubMedCentralCrossRefPubMed Yang Y, Shaffer AL 3rd, Emre NC, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21:723–37. PubMedCentralCrossRefPubMed
14.
Zurück zum Zitat Kritharis A, Coyle M, Sharma J, et al. Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities. Blood. 2015;125(16):2471–6. CrossRefPubMed Kritharis A, Coyle M, Sharma J, et al. Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities. Blood. 2015;125(16):2471–6. CrossRefPubMed
15.
Zurück zum Zitat Wiernik PH, Lossos IS, Tuscano JM, et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26:4952–7. CrossRefPubMed Wiernik PH, Lossos IS, Tuscano JM, et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26:4952–7. CrossRefPubMed
16.
Zurück zum Zitat Witzig TE, Vose JM, Zinzani PL, et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann Oncol. 2011;22:1622–7. CrossRefPubMed Witzig TE, Vose JM, Zinzani PL, et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann Oncol. 2011;22:1622–7. CrossRefPubMed
17.
Zurück zum Zitat Zinzani PL, Pellegrini C, Gandolfi L, et al. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011;11:462–6. CrossRefPubMed Zinzani PL, Pellegrini C, Gandolfi L, et al. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011;11:462–6. CrossRefPubMed
18.
Zurück zum Zitat Wang M, Fowler N, Wagner-Bartak N, et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013;27:1902–9. CrossRefPubMed Wang M, Fowler N, Wagner-Bartak N, et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013;27:1902–9. CrossRefPubMed
19.
Zurück zum Zitat Feldman T, Mato AR, Chow KF, et al. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014;166:77–83. PubMedCentralCrossRefPubMed Feldman T, Mato AR, Chow KF, et al. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014;166:77–83. PubMedCentralCrossRefPubMed
20.
Zurück zum Zitat Czuczman MS, Davies A, Linton KM, et al. A Phase 2/3 Multicenter, Randomized Study Comparing the Efficacy and Safety of Lenalidomide Versus Investigator’s Choice in Relapsed/Refractory DLBCL. ASH Annual Meeting Abstracts. 2014;124. Czuczman MS, Davies A, Linton KM, et al. A Phase 2/3 Multicenter, Randomized Study Comparing the Efficacy and Safety of Lenalidomide Versus Investigator’s Choice in Relapsed/Refractory DLBCL. ASH Annual Meeting Abstracts. 2014;124.
21.
Zurück zum Zitat Chiappella A, Tucci A, Castellino A, et al. Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. Haematologica. 2013;98:1732–8. PubMedCentralCrossRefPubMed Chiappella A, Tucci A, Castellino A, et al. Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. Haematologica. 2013;98:1732–8. PubMedCentralCrossRefPubMed
22.
Zurück zum Zitat Vitolo U, Chiappella A, Franceschetti S, et al. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014;15:730–7. CrossRefPubMed Vitolo U, Chiappella A, Franceschetti S, et al. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014;15:730–7. CrossRefPubMed
23.
Zurück zum Zitat Nowakowski GS, LaPlant B, Macon WR, et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-Cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J Clin Oncol. 2015;33(3):251–7. CrossRefPubMed Nowakowski GS, LaPlant B, Macon WR, et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-Cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J Clin Oncol. 2015;33(3):251–7. CrossRefPubMed
24.
Zurück zum Zitat Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, et al. Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer. 2011;117(22):5058–66. CrossRefPubMed Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, et al. Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer. 2011;117(22):5058–66. CrossRefPubMed
25.
Zurück zum Zitat Aalipour A, AdvaniRH. Bruton tyrosine kinase inhibitors: a promising novel targeted treatment for B cell lymphomas. Br J Haematol. 2013;163(4):436–43. PubMedCentralCrossRefPubMed Aalipour A, AdvaniRH. Bruton tyrosine kinase inhibitors: a promising novel targeted treatment for B cell lymphomas. Br J Haematol. 2013;163(4):436–43. PubMedCentralCrossRefPubMed
26.
27.
Zurück zum Zitat 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(1):88–94. CrossRefPubMed 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(1):88–94. CrossRefPubMed
28.
Zurück zum Zitat Wilson W, Gerecitano J, Goy A, et al. The bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), has preferential activity in the abc subtype of relapsed/refractory de novo diffuse large b-cell lymphoma (DLBCL): interim results of a multicenter, open-label, phase 2 study. Blood. 2012;120(21):a686. Wilson W, Gerecitano J, Goy A, et al. The bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), has preferential activity in the abc subtype of relapsed/refractory de novo diffuse large b-cell lymphoma (DLBCL): interim results of a multicenter, open-label, phase 2 study. Blood. 2012;120(21):a686.
29.
Zurück zum Zitat Younes A, Thieblemont C, Morschhauser F, et al. Combination of ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment-naive patients with CD20-positive B-cell non-Hodgkin lymphoma: a non-randomised, phase 1b study. Lancet Oncol. 2014;15(9):1019–26. CrossRefPubMed Younes A, Thieblemont C, Morschhauser F, et al. Combination of ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment-naive patients with CD20-positive B-cell non-Hodgkin lymphoma: a non-randomised, phase 1b study. Lancet Oncol. 2014;15(9):1019–26. CrossRefPubMed
30.
Zurück zum Zitat Gelman JS, Sironi J, Berezniuk I, et al. Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib. PLoS One. 2013;8(1):e53263. PubMedCentralCrossRefPubMed Gelman JS, Sironi J, Berezniuk I, et al. Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib. PLoS One. 2013;8(1):e53263. PubMedCentralCrossRefPubMed
31.
Zurück zum Zitat McCormack PL. Bortezomib: a review in mantle cell lymphoma in previously untreated patients unsuitable for stem-cell transplantation. BioDrugs. 2015;29(3):207–14. CrossRefPubMed McCormack PL. Bortezomib: a review in mantle cell lymphoma in previously untreated patients unsuitable for stem-cell transplantation. BioDrugs. 2015;29(3):207–14. CrossRefPubMed
32.
Zurück zum Zitat Awan FT, Flynn JM, Jones JA, et al. Phase I dose escalation trial of the novel proteasome inhibitor carfilzomib in patients with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma. Leuk Lymphoma. 2015;11:1–7. [Epub ahead of print]. CrossRef Awan FT, Flynn JM, Jones JA, et al. Phase I dose escalation trial of the novel proteasome inhibitor carfilzomib in patients with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma. Leuk Lymphoma. 2015;11:1–7. [Epub ahead of print]. CrossRef
33.
Zurück zum Zitat Tsujimoto Y, Finger LR, Yunis J, et al. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984;226(4678):1097–9. CrossRefPubMed Tsujimoto Y, Finger LR, Yunis J, et al. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984;226(4678):1097–9. CrossRefPubMed
34.
Zurück zum Zitat Oki Y, Noorani M, Lin P, et al. Double hit lymphoma: the MD Anderson Cancer Center clinical experience. Br J Haematol. 2014;166(6):891–901. CrossRefPubMed Oki Y, Noorani M, Lin P, et al. Double hit lymphoma: the MD Anderson Cancer Center clinical experience. Br J Haematol. 2014;166(6):891–901. CrossRefPubMed
35.
Zurück zum Zitat Kurtz JE, Ray-Coquard I. PI3 kinase inhibitors in the clinic: an update. Anticancer Res. 2012;32(7):2463–70. PubMed Kurtz JE, Ray-Coquard I. PI3 kinase inhibitors in the clinic: an update. Anticancer Res. 2012;32(7):2463–70. PubMed
36.
Zurück zum Zitat Merli M, Ferrario A, Maffioli M, et al. Everolimus in diffuse large B-cell lymphomas. Future Oncol. 2015;11(3):373–83. CrossRefPubMed Merli M, Ferrario A, Maffioli M, et al. Everolimus in diffuse large B-cell lymphomas. Future Oncol. 2015;11(3):373–83. CrossRefPubMed
37.
Zurück zum Zitat Wang M, Popplewell LL, Collins RH Jr, et al. Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib: multicentre, single-arm, phase 2 study. Br J Haematol. 2014;165(4):510–8. CrossRefPubMed Wang M, Popplewell LL, Collins RH Jr, et al. Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib: multicentre, single-arm, phase 2 study. Br J Haematol. 2014;165(4):510–8. CrossRefPubMed
38.
Zurück zum Zitat Shah A, Mangaonkar A. Idelalisib: A novel PI3Kδ inhibitor for chronic lymphocytic leukemia. Ann Pharmacother. 2015. [Epub ahead of print]. Shah A, Mangaonkar A. Idelalisib: A novel PI3Kδ inhibitor for chronic lymphocytic leukemia. Ann Pharmacother. 2015. [Epub ahead of print].
Metadaten
Titel
Changing treatment paradigms in lymphoma: new targets and new drugs
verfasst von
MD Michael Mian
MD Annalisa Chiappella
Publikationsdatum
01.09.2015
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 3/2015
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-015-0229-1

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