Skip to main content
Erschienen in:

19.11.2018 | short review

Diffuse large B‑cell lymphoma

verfasst von: David Fuchs

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Summary

Since the introduction of anti-CD20 antibodies and polychemotherapy, diffuse large B‑cell lymphoma (DLBCL) has become a treatable, and, for a high proportion of patients, curable disease. However, a sizeable proportion of patients, especially in poor-prognosis subgroups, will relapse.
The landscape of therapy in DLBCL has seen some exciting changes in the past years, most notably with the introduction of CAR-T-cell therapy. All three major trials were recently updated and showed sustained responses and excellent preliminary survival data.
Other immunotherapies are gaining ground as well, as the antibody–drug conjugate polatuzumab vedotin has shown to be effective in relapsed DLBCL in combination with chemo-immunotherapy (rituximab and bendamustine). Complete remission rates increased from 15 to 40% and overall survival from 4.7 to 11.8 months. Polatuzumab is also being studied in previously untreated patients and results are awaited in 2019.
Checkpoint inhibitors, the mainstay of therapy in a variety of malignancies, are also being studied in DLBCL. Interim results of an ongoing phase I/II study of atezolizumab with R‑CHOP in previously untreated patients show 83% complete remissions in early data.
Other novel substances, like anti-CD47-antibodies and PI3-kinase inhibitors, show promising efficacy in early trials in relapsed patients as well.
Literatur
1.
Zurück zum Zitat Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040–5.CrossRef Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040–5.CrossRef
2.
Zurück zum Zitat Merron B, Davies A. Double hit lymphoma: How do we define it and how do we treat it? Best Pract Res Clin Haematol. 2018;31(3):233–40.CrossRef Merron B, Davies A. Double hit lymphoma: How do we define it and how do we treat it? Best Pract Res Clin Haematol. 2018;31(3):233–40.CrossRef
3.
Zurück zum Zitat Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.CrossRef Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.CrossRef
4.
Zurück zum Zitat Thieblemont C, Bernard S, Meignan M, et al. Optimizing initial therapy in DLBCL. Best Pract Res Clin Haematol. 2018;31(3):199–208.CrossRef Thieblemont C, Bernard S, Meignan M, et al. Optimizing initial therapy in DLBCL. Best Pract Res Clin Haematol. 2018;31(3):199–208.CrossRef
5.
Zurück zum Zitat Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B‑cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–8.CrossRef Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B‑cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–8.CrossRef
6.
Zurück zum Zitat Younes A. Brentuximab vedotin for the treatment of patients with Hodgkin lymphoma. Hematol Oncol Clin North Am. 2014;28:27–32.CrossRef Younes A. Brentuximab vedotin for the treatment of patients with Hodgkin lymphoma. Hematol Oncol Clin North Am. 2014;28:27–32.CrossRef
7.
Zurück zum Zitat EMILIA Study Group, Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.CrossRef EMILIA Study Group, Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.CrossRef
8.
Zurück zum Zitat Dornan D, Bennett F, Chen Y, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009;114:2721–9.CrossRef Dornan D, Bennett F, Chen Y, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009;114:2721–9.CrossRef
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;16:704–15.CrossRef 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;16:704–15.CrossRef
10.
Zurück zum Zitat Morschhauser F, Flinn I, Advani RH, et al. Updated results of a phase II randomized study (ROMULUS) of polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed/refractory non-Hodgkin lymphoma. Blood. 2014;124:4457. Morschhauser F, Flinn I, Advani RH, et al. Updated results of a phase II randomized study (ROMULUS) of polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed/refractory non-Hodgkin lymphoma. Blood. 2014;124:4457.
11.
Zurück zum Zitat Sehn LH. Randomized phase 2 trial of polatuzumab vedotin (pola) with bendamustine and rituximab (BR) in relapsed/refractory (r/r) FL and DLBCL. J Clin Oncol. 2018;36(suppl):7507.CrossRef Sehn LH. Randomized phase 2 trial of polatuzumab vedotin (pola) with bendamustine and rituximab (BR) in relapsed/refractory (r/r) FL and DLBCL. J Clin Oncol. 2018;36(suppl):7507.CrossRef
12.
Zurück zum Zitat Tilly H, Sharman J, Bartlett N, et al. Pola-R-CHP: polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, prednisone for patients with previously untreated diffuse large B‑cell lymphoma. Hematol Oncol. 2017;35:90–1.CrossRef Tilly H, Sharman J, Bartlett N, et al. Pola-R-CHP: polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, prednisone for patients with previously untreated diffuse large B‑cell lymphoma. Hematol Oncol. 2017;35:90–1.CrossRef
13.
Zurück zum Zitat Tilly H, et al. A phase 3 study comparing polatuzumab vedotin plus R‑CHP versus R‑CHOP in patients with DLBCL (POLARIX). J Clin Oncol. 2018;36(suppl):TPS7589.CrossRef Tilly H, et al. A phase 3 study comparing polatuzumab vedotin plus R‑CHP versus R‑CHOP in patients with DLBCL (POLARIX). J Clin Oncol. 2018;36(suppl):TPS7589.CrossRef
14.
Zurück zum Zitat Juarez-Salcedoa LM, Sandoval-Susb JJ, Sokol L. The role of anti-PD-1 and anti-PD-L1 agents in the treatment of diffuse large B‑cell lymphoma: the future is now. Crit Rev Oncol Hematol. 2017;113:52–62.CrossRef Juarez-Salcedoa LM, Sandoval-Susb JJ, Sokol L. The role of anti-PD-1 and anti-PD-L1 agents in the treatment of diffuse large B‑cell lymphoma: the future is now. Crit Rev Oncol Hematol. 2017;113:52–62.CrossRef
15.
Zurück zum Zitat Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase ib study. J Clin Oncol. 2016;34(23):2698–704.CrossRef Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase ib study. J Clin Oncol. 2016;34(23):2698–704.CrossRef
16.
Zurück zum Zitat Till BG, Park SI, Popplewell LL, et al. Safety and clinical activity of Atezolizumab (anti-PDL1) in combination with obinutuzumab in patients with relapsed or refractory Non-Hodgkin Lymphoma. Blood. 2015;126(23):5104. Till BG, Park SI, Popplewell LL, et al. Safety and clinical activity of Atezolizumab (anti-PDL1) in combination with obinutuzumab in patients with relapsed or refractory Non-Hodgkin Lymphoma. Blood. 2015;126(23):5104.
17.
Zurück zum Zitat Ansell S, Gutierrez ME, Shipp MA, et al. A phase 1 study of nivolumab in combination with Ipilimumab for relapsed or refractory hematologic malignancies (checkmate 039). Blood. 2016;128(22):183. Ansell S, Gutierrez ME, Shipp MA, et al. A phase 1 study of nivolumab in combination with Ipilimumab for relapsed or refractory hematologic malignancies (checkmate 039). Blood. 2016;128(22):183.
18.
Zurück zum Zitat Younes A, Burke JM, Diefenbach C, et al. Atezolizumab plus R‑CHOP shows ecouraging activity and acceptable toxicity in untreated patients with diffuse large B‑cell lymphoma (DLBCL): an interim analysis of a phase I/II study. EHA Learning Center. 2018. p. 214450. Younes A, Burke JM, Diefenbach C, et al. Atezolizumab plus R‑CHOP shows ecouraging activity and acceptable toxicity in untreated patients with diffuse large B‑cell lymphoma (DLBCL): an interim analysis of a phase I/II study. EHA Learning Center. 2018. p. 214450.
19.
Zurück zum Zitat Nair R, Neelapu SS. The promise of CAR T‑cell therapy in aggressive B‑cell lymphoma. Best Pract Res Clin Haematol. 2018;31(3):293–8.CrossRef Nair R, Neelapu SS. The promise of CAR T‑cell therapy in aggressive B‑cell lymphoma. Best Pract Res Clin Haematol. 2018;31(3):293–8.CrossRef
20.
Zurück zum Zitat Locke FL, Ghobadi A, Jacobson CA, et al. Durability of response in ZUMA-1, the pivotal phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients (Pts) with refractory large B‑cell lymphoma. J Clin Oncol. 2018;36(suppl):3003.CrossRef Locke FL, Ghobadi A, Jacobson CA, et al. Durability of response in ZUMA-1, the pivotal phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients (Pts) with refractory large B‑cell lymphoma. J Clin Oncol. 2018;36(suppl):3003.CrossRef
21.
Zurück zum Zitat Locke FL, Ghobadi A, Lekakis LJ, et al. Axicabtagene ciloleucel (Axi-Cel) in patients with refractory large B cell lymphoma: outcomes by prior lines of therapy in ZUMA-1. EHA Learning Center. 2018. p. 214449. Locke FL, Ghobadi A, Lekakis LJ, et al. Axicabtagene ciloleucel (Axi-Cel) in patients with refractory large B cell lymphoma: outcomes by prior lines of therapy in ZUMA-1. EHA Learning Center. 2018. p. 214449.
22.
Zurück zum Zitat Borchmann P, Tam CS, Jäger U, et al. An updated analysis of JULIET, a global pivotal phase II trial of tisagenlecleucel in adult patients with relapsed or refractory (r/r) diffuse large B cell lymphoma (DLBCL). EHA Learning Center. 2018. p. 214521. Borchmann P, Tam CS, Jäger U, et al. An updated analysis of JULIET, a global pivotal phase II trial of tisagenlecleucel in adult patients with relapsed or refractory (r/r) diffuse large B cell lymphoma (DLBCL). EHA Learning Center. 2018. p. 214521.
23.
Zurück zum Zitat Abramson JS, Gordon LI, Palomba ML, et al. Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL. J Clin Oncol. 2018;36(suppl):7505.CrossRef Abramson JS, Gordon LI, Palomba ML, et al. Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL. J Clin Oncol. 2018;36(suppl):7505.CrossRef
24.
Zurück zum Zitat Advani RH, Flinn I, Popplewell L, et al. Activity and tolerabilty of the first-in-class anti-CD47 antibody Hu5F9-G4 with rituximab tolerated in relapsed/refractory non-Hodgkin lymphoma: Initial phase 1b/2 results. J Clin Oncol. 2018;36(suppl):7504.CrossRef Advani RH, Flinn I, Popplewell L, et al. Activity and tolerabilty of the first-in-class anti-CD47 antibody Hu5F9-G4 with rituximab tolerated in relapsed/refractory non-Hodgkin lymphoma: Initial phase 1b/2 results. J Clin Oncol. 2018;36(suppl):7504.CrossRef
25.
Zurück zum Zitat Jurczak W, Zinzani PL, Gaidano G, et al. Single-agent MOR208 in relapsed or refractory (R-R) non-Hodgkin’s Lymphoma (NHL): results from diffuse large B‑cell lymphoma (DLBCL) and indolent NHL subgroups of a phase IIa study. Blood. 2016;128(22):623. Jurczak W, Zinzani PL, Gaidano G, et al. Single-agent MOR208 in relapsed or refractory (R-R) non-Hodgkin’s Lymphoma (NHL): results from diffuse large B‑cell lymphoma (DLBCL) and indolent NHL subgroups of a phase IIa study. Blood. 2016;128(22):623.
26.
Zurück zum Zitat Salles GA, Duell J, González-Barca E, et al. Single-arm phase II study of MOR208 combined with Lenalidomide in patients with relapsed or refractory diffuse large B‑cell lymphoma: L‑mind. Blood. 2017;130(Suppl 1):4123. Salles GA, Duell J, González-Barca E, et al. Single-arm phase II study of MOR208 combined with Lenalidomide in patients with relapsed or refractory diffuse large B‑cell lymphoma: L‑mind. Blood. 2017;130(Suppl 1):4123.
27.
Zurück zum Zitat Barr PM, Smith SD, Roschewski MJ, et al. Acalabrutinib combined with PI3Kδ inhibitor ACP-319 in patients (pts) with relapsed/refractory (R/R) B‑cell malignancies. J Clin Oncol. 2018;36(suppl):7518.CrossRef Barr PM, Smith SD, Roschewski MJ, et al. Acalabrutinib combined with PI3Kδ inhibitor ACP-319 in patients (pts) with relapsed/refractory (R/R) B‑cell malignancies. J Clin Oncol. 2018;36(suppl):7518.CrossRef
28.
Zurück zum Zitat Batlevi CL, De Frank S, Stewart C, et al. Phase I/II clinical trial of ibrutinib and buparlisib in relapsed/refractory diffuse large B‑cell lymphoma, mantle cell lymphoma, and follicular lymphoma. J Clin Oncol. 2018;36(suppl):7520.CrossRef Batlevi CL, De Frank S, Stewart C, et al. Phase I/II clinical trial of ibrutinib and buparlisib in relapsed/refractory diffuse large B‑cell lymphoma, mantle cell lymphoma, and follicular lymphoma. J Clin Oncol. 2018;36(suppl):7520.CrossRef
Metadaten
Titel
Diffuse large B‑cell lymphoma
verfasst von
David Fuchs
Publikationsdatum
19.11.2018
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 1/2019
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-018-0457-2