Top

Published in:

Open Access 01-12-2019 | Lymphoma | Review

Novel and emerging therapies for B cell lymphoma

Authors: Sabarish Ayyappan, Kami Maddocks

Published in: Journal of Hematology & Oncology | Issue 1/2019

Abstract

Lymphomas are a heterogeneous group of lymphoproliferative disorders, with unique clinical and biological characteristics that exhibit variable response to therapy. Advances in chemo-immunotherapy have improved outcomes in a number of lymphoma subtypes; however, the prognosis for many patients with relapsed and refractory disease remains poor. Novel therapies including several small molecule inhibitors and chimeric antigen receptor T cells have been approved for the treatment of different lymphoma subtypes at relapse, changing the therapy landscape and further improving survival in many of these diseases. This has led to a focus on the development of new cellular therapy, antibody-based therapy, and small molecule inhibitors for relapsed and refractory disease that offer an alternative approach to cytotoxic chemotherapy. We will review these promising novel therapies and discuss their safety and efficacy in first in human studies.

Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.PubMedCrossRef

Gandhi L, Garassino MC. Pembrolizumab plus chemotherapy in lung cancer. N Engl J Med. 2018;379(11):e18.PubMedCrossRef

Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.PubMedPubMedCentralCrossRef

Mittal D, Gubin MM, Schreiber RD, Smyth MJ. New insights into cancer immunoediting and its three component phases--elimination, equilibrium and escape. Curr Opin Immunol. 2014;27:16–25.PubMedPubMedCentralCrossRef

Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science (New York, NY). 2011;331(6024):1565–70.CrossRef

Cohen JE, Merims S, Frank S, Engelstein R, Peretz T, Lotem M. Adoptive cell therapy: past, present and future. Immunotherapy. 2017;9(2):183–96.PubMedCrossRef

FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome [press release]. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm574154.htm, Accessed 3 Mar 2019 2017.

FDA approves tisagenlecleucel for adults with relapsed or refractory large B-cell lymphoma [press release]. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm606540.htm, Accessed 3 Mar 2019 2018.

Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45–56.PubMedCrossRef

10.

FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma [press release]. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm581216.htm, Accessed 30 Mar 2019 2017.

11.

Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44.PubMedPubMedCentralCrossRef

12.

Abramson JS, Gordon LI, Palomba ML, Lunning MA, Arnason JE, Forero-Torres A, 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(15_suppl):7505.CrossRef

13.

Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31–42.PubMedCrossRef

14.

Borchmann P. An updated analysis of JULIET, a global pivotal phase 2 trial of tisagenlecleucel in adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL). HemaSphere. 2018;2(S1):1–1113.

15.

Hopfinger G, Jäger U, Worel N. CAR-T Cell Therapy in diffuse large B cell lymphoma: hype and hope. HemaSphere. 2019;3(2):e185.CrossRefPubMedPubMedCentral

16.

Santomasso BD, Park JH, Salloum D, Riviere I, Flynn J, Mead E, et al. Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov. 2018;8(8):958–71.PubMedCrossRefPubMedCentral

17.

Liu H, Horan LH, Grupp SA, Barrett DM, Liu C. Abstract 1537: Anti-CD19 ARTEMIS™ T cells prevent excessive inflammatory cytokine release, including IL-6, in a co-culture model of CRS. Cancer Res. 2018;78(13 Supplement):1537.

18.

Ying ZT, Long L, Liu H, Zhang M, He P, Rizzieri D, et al. ET190L1-ARTEMIS T cell therapy to induce complete remission of relapsed and refractory (r/r) B-cell lymphoma with no cytokine release syndrome in the first-in-human clinical study. J Clin Oncol. 2018;36(15_suppl):3049.CrossRef

19.

Ying Z, Long L, Liu H, Song Y, Rizzieri DA, Nejadnik B, et al. ET190L1-Artemis T cell therapy results in durable disease remissions with no cytokine release syndrome or neurotoxicity in patients with relapsed and refractory B-cell lymphoma. Blood. 2018;132(Suppl 1):1689.

20.

Shalabi H, Kraft IL, Wang HW, Yuan CM, Yates B, Delbrook C, et al. Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma. Haematologica. 2018;103(5):e215–e8.PubMedPubMedCentralCrossRef

21.

Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2017;24:20.PubMedPubMedCentralCrossRef

22.

Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015;5(12):1282–95.PubMedPubMedCentralCrossRef

23.

Hossain N, Sahaf B, Abramian M, Spiegel JY, Kong K, Kim S, et al. Phase I experience with a bi-specific CAR targeting CD19 and CD22 in adults with B-cell malignancies. Blood. 2018;132(Suppl 1):490.

24.

Shah NN, Zhu F, Taylor C, Schneider D, Krueger W, Worden A, et al. A phase 1 study with point-of-care manufacturing of dual targeted, tandem anti-CD19, anti-CD20 chimeric antigen receptor modified T (CAR-T) cells for relapsed, refractory, non-Hodgkin lymphoma. Blood. 2018;132(Suppl 1):4193.

25.

Ardeshna K, Marzolini MAV, Osborne W, Al-Hajj M, Thomas S, Faulkner J, et al. Study of AUTO3, the first bicistronic chimeric antigen receptor (CAR) targeting CD19 and CD22, followed by anti-PD1 consolidation in patients with relapsed/refractory (r/r) diffuse large B cell lymphoma (DLBCL): Alexander Study. Blood. 2018;132(Suppl 1):1679.

26.

Park JH, Palomba ML, Batlevi CL, Riviere I, Wang X, Senechal B, et al. A phase I first-in-human clinical trial of CD19-targeted 19-28z/4-1BBL “armored” CAR T cells in patients with relapsed or refractory NHL and CLL including Richter’s transformation. Blood. 2018;132(Suppl 1):224.

27.

Akard LP, Jaglowski S, Devine SM, McKinney MS, Vasconcelles M, Huet H, et al. ACTR087, autologous T lymphocytes expressing antibody coupled T-cell receptors (ACTR), induces complete responses in patients with relapsed or refractory CD20-positive B-cell lymphoma, in combination with rituximab. Blood. 2017;130(Suppl 1):580.

28.

Flinn IW, Cohen JB, Akard LP, Jaglowski S, Vasconcelles M, Ranger A, et al. Preliminary clinical results of a phase 1 study evaluating the safety and anti-tumor activity of ACTR707 in combination with rituximab in subjects with relapsed or refractory CD20+ B-cell lymphoma. Blood. 2018;132(Suppl 1):2966.

29.

Zhao Z, Condomines M, van der Stegen SJC, Perna F, Kloss CC, Gunset G, et al. Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells. Cancer Cell. 2015;28(4):415–28.PubMedPubMedCentralCrossRef

30.

Grupp SA, Maude SL, Shaw PA, Aplenc R, Barrett DM, Callahan C, et al. Durable remissions in children with relapsed/refractory ALL treated with T cells engineered with a CD19-targeted chimeric antigen receptor (CTL019). Blood. 2015;126(23):681.

31.

Huet HA, Judge C, Barnitz RA, Boomer R, McGinness K, Shin J, et al. Targeting CD20+ Relapsed refractory B cell lymphoma with ACTR087, antibody-coupled T-cell receptor (ACTR) engineered autologous T cells, in combination with rituximab. Blood. 2016;128(22):3512.

32.

Kudo K, Imai C, Lorenzini P, Kamiya T, Kono K, Davidoff AM, et al. T Lymphocytes expressing a CD16 signaling receptor exert antibody-dependent cancer cell killing. Cancer Res. 2014;74(1):93–103.PubMedCrossRef

33.

Goebeler M-E, Knop S, Viardot A, Kufer P, Topp MS, Einsele H, et al. Bispecific T-cell engager (BiTE) antibody construct blinatumomab for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma: final results from a phase I study. J Clin Oncol. 2016;34(10):1104–11.PubMedCrossRef

34.

Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, et al. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016;127(11):1410–6.PubMedPubMedCentralCrossRef

35.

Hutchings M, Iacoboni G, Morschhauser F, Offner F, Sureda A, Salles GA, et al. CD20-Tcb (RG6026), a novel “2:1” format T-cell-engaging bispecific antibody, induces complete remissions in relapsed/refractory B-cell non-Hodgkin’s lymphoma: preliminary results from a phase I first in human trial. Blood. 2018;132(Suppl 1):226.

36.

Budde LE, Sehn LH, Assouline S, Flinn IW, Isufi I, Yoon S-S, et al. Mosunetuzumab, a full-length bispecific CD20/CD3 antibody, displays clinical activity in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL): interim safety and efficacy results from a phase 1 study. Blood. 2018;132(Suppl 1):399.

37.

Caimi P, Kahl BS, Hamadani M, Carlo-Stella C, He S, Ungar D, et al. Safety and efficacy of Adct-402 (loncastuximab tesirine), a novel antibody drug conjugate, in relapsed/refractory follicular lymphoma and mantle cell lymphoma: interim results from the phase 1 first-in-human study. Blood. 2018;132(Suppl 1):2874.

38.

Collins GP, Horwitz SM, Davies A, Karnad A, Samaniego F, Spira AI, et al. Adct-301 (camidanlumab tesirine), a novel pyrrolobenzodiazepine-based CD25-targeting antibody drug conjugate, in a phase 1 study of relapsed/refractory non-Hodgkin lymphoma shows activity in T-cell lymphoma. Blood. 2018;132(Suppl 1):1658.

39.

Hamadani M, Collins GP, Samaniego F, Spira AI, Davies A, Radford J, et al. Phase 1 study of Adct-301 (camidanlumab tesirine), a novel pyrrolobenzodiazepine-based antibody drug conjugate, in relapsed/refractory classical Hodgkin lymphoma. Blood. 2018;132(Suppl 1):928.

40.

Fanale MA, Hamlin PA, Park SI, Persky DO, Higgins JP, Burnett C, et al. Safety and efficacy of anti-CD20 immunotoxin MT-3724 in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) in a phase I study. J Clin Oncol. 2018;36(15_suppl):7580.CrossRef

41.

Advani R, Flinn I, Popplewell L, Forero A, Bartlett NL, Ghosh N, et al. CD47 Blockade by Hu5F9-G4 and rituximab in non-Hodgkin’s lymphoma. N Engl J Med. 2018;379(18):1711–21.PubMedCrossRefPubMedCentral

42.

Herrera AF, Patel MR, Burke JM, Advani RH, Cheson BD, Sharman JP, et al. A phase I study of the anti-CD79b THIOMAB-drug conjugate DCDS0780A in patients (pts) with relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL). Blood. 2017;130(Suppl 1):4129.

43.

Kolstad A, Madsbu U, Beasley M, Bayne M, Illidge TM, O’Rourke N, et al. 177 Lu-lilotomab satetraxetan, a novel CD37-targeted antibody-radionuclide conjugate in relapsed non-Hodgkin’s lymphoma (NHL): updated results of an ongoing phase I/II study (LYMRIT 37-01). Blood. 2017;130(Suppl 1):2769.

44.

Mossner E, Brunker P, Moser S, Puntener U, Schmidt C, Herter 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.PubMedPubMedCentralCrossRef

45.

Nagorsen D, Kufer P, Baeuerle PA, Bargou R. Blinatumomab: a historical perspective. Pharmacol Ther. 2012;136(3):334–42.PubMedCrossRef

46.

Nagorsen D, Baeuerle PA. Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res. 2011;317(9):1255–60.PubMedCrossRef

47.

Haas C, Krinner E, Brischwein K, Hoffmann P, Lutterbuse R, Schlereth B, et al. Mode of cytotoxic action of T cell-engaging BiTE antibody MT110. Immunobiology. 2009;214(6):441–53.PubMedCrossRef

48.

Löffler A, Kufer P, Lutterbüse R, Zettl F, Daniel PT, Schwenkenbecher JM, et al. A recombinant bispecific single-chain antibody, CD19 × CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood. 2000;95(6):2098–103.PubMed

49.

Schlereth B, Quadt C, Dreier T, Kufer P, Lorenczewski G, Prang N, et al. T-cell activation and B-cell depletion in chimpanzees treated with a bispecific anti-CD19/anti-CD3 single-chain antibody construct. Cancer Immunol Immunother. 2006;55(5):503–14.PubMedCrossRef

50.

Bacac M, Fauti T, Sam J, Colombetti S, Weinzierl T, Ouaret D, et al. A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumors. Clin Cancer Res. 2016;22(13):3286–97.PubMedCrossRef

51.

Bacac M, Klein C, Umana P. CEA TCB: A novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors. Oncoimmunology. 2016;5(8):e1203498.PubMedPubMedCentralCrossRef

52.

Bacac M, Colombetti S, Herter S, Sam J, Perro M, Chen S, et al. CD20-TCB with obinutuzumab pretreatment as next-generation treatment of hematologic malignancies. Clin Cancer Res. 2018;24(19):4785–97.PubMedCrossRef

53.

Sun LL, Ellerman D, Mathieu M, Hristopoulos M, Chen X, Li Y, et al. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015;7(287):287ra70.PubMedCrossRef

54.

Zammarchi F, Corbett S, Adams L, Tyrer PC, Kiakos K, Janghra N, et al. ADCT-402, a PBD dimer-containing antibody drug conjugate targeting CD19-expressing malignancies. Blood. 2018. https://doi.org/10.1182/blood-2017-10-813493.PubMedCrossRef

55.

Radford J, Kahl BS, Hamadani M, Carlo-Stella C, Caimi P, Ardeshna KM, et al. Interim results from the first-in-human clinical trial of Adct-402 (loncastuximab tesirine), a novel pyrrolobenzodiazepine-based antibody drug conjugate, in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2018;132(Suppl 1):398.

56.

Strauchen JA, Breakstone BA. IL-2 receptor expression in human lymphoid lesions. Immunohistochemical study of 166 cases. Am J Pathol. 1987;126(3):506–12.PubMedPubMedCentral

57.

Flynn MJ, Zammarchi F, Tyrer PC, Akarca AU, Janghra N, Britten CE, et al. ADCT-301, a pyrrolobenzodiazepine (PBD) dimer-containing antibody-drug conjugate (ADC) targeting CD25-expressing hematological malignancies. Mol Cancer Ther. 2016;15(11):2709–21.PubMedCrossRef

58.

Willert EK, Robinson GL, Rajagopalan S, Brieschke B, Erdman J, Neill J, et al. Abstract 2477: Engineered toxin bodies: a next-generation immunotoxin scaffold with novel immuno-oncology functionality. Cancer Res. 2015;75(15 Supplement):2477.

59.

Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S, et al. Anti-CD47 Antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell. 2010;142(5):699–713.PubMedPubMedCentralCrossRef

60.

Liu J, Wang L, Zhao F, Tseng S, Narayanan C, Shura L, et al. pre-clinical development of a humanized anti-CD47 antibody with anti-cancer therapeutic potential. PloS one. 2015;10(9):e0137345-e.PubMedPubMedCentralCrossRef

61.

Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56–61.PubMedCrossRef

62.

Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.PubMedCrossRef

63.

Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T, O’Donnell E, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116(17):3268–77.PubMedPubMedCentralCrossRef

64.

Roemer MG, Advani RH, Ligon AH, Natkunam Y, Redd RA, Homer H, et al. PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol. 2016;34(23):2690–7.PubMedPubMedCentralCrossRef

65.

Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, et al. Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II CheckMate 205 Trial. J Clin Oncol. 2018;36(14):1428–39.PubMedPubMedCentralCrossRef

66.

Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 2017;35(19):2125–32.PubMedPubMedCentralCrossRef

67.

Ansell S, Gutierrez ME, Shipp MA, Gladstone D, Moskowitz A, Borello I, 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.

68.

Herrera AF, Moskowitz AJ, Bartlett NL, Vose JM, Ramchandren R, Feldman TA, et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018;131(11):1183–94.PubMedPubMedCentralCrossRef

69.

Ramchandren R, Fanale MA, Rueda A, Armand P, Trněný M, Feldman TA, et al. Nivolumab for newly diagnosed advanced-stage classical Hodgkin lymphoma (cHL): results from the phase 2 Checkmate 205 Study. Blood. 2017;130(Suppl 1):651.

70.

Chapuy B, Roemer MG, Stewart C, Tan Y, Abo RP, Zhang L, et al. Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood. 2016;127(7):869–81.PubMedPubMedCentralCrossRef

71.

Zinzani PL, Ribrag V, Moskowitz CH, Michot JM, Kuruvilla J, Balakumaran A, et al. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017;130(3):267–70.PubMedPubMedCentralCrossRef

72.

Nayak L, Iwamoto FM, LaCasce A, Mukundan S, Roemer MGM, Chapuy B, et al. PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood. 2017;129(23):3071–3.PubMedPubMedCentralCrossRef

73.

Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG, Xu ML, et al. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013;19(13):3462–73.PubMedPubMedCentralCrossRef

74.

Van Roosbroeck K, Ferreiro JF, Tousseyn T, van der Krogt JA, Michaux L, Pienkowska-Grela B, et al. Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies. Genes Chromosomes Cancer. 2016;55(5):428–41.PubMedCrossRef

75.

Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, 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.PubMedPubMedCentralCrossRef

76.

Andorsky DJ, Yamada RE, Said J, Pinkus GS, Betting DJ, Timmerman JM. Programmed death ligand 1 is expressed by non-Hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res. 2011;17(13):4232–44.PubMedCrossRef

77.

Smeltzer JP, Jones JM, Ziesmer SC, Grote DM, Xiu B, Ristow KM, et al. Pattern of CD14+ follicular dendritic cells and PD1+ T cells independently predicts time to transformation in follicular lymphoma. Clin Cancer Res. 2014;20(11):2862–72.PubMedPubMedCentralCrossRef

78.

Yang ZZ, Grote DM, Ziesmer SC, Xiu B, Novak AJ, Ansell SM. PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer J. 2015;5:e281.PubMedPubMedCentralCrossRef

79.

Palomba ML, Till BG, Park SI, Morschhauser F, Cartron G, Marks R, et al. A phase Ib study evaluating the safety and clinical activity of atezolizumab combined with obinutuzumab in patients with relapsed or refractory non-Hodgkin lymphoma (NHL). Hematol Oncol. 2017;35(S2):137–8.CrossRef

80.

Jurczak W, Rule S, Townsend W, Tucker D, Sarholz B, Scheele J, et al. A phase I/II, first in human trial of the Bruton’s tyrosine kinase inhibitor M7583 in patients with B-cell malignancies. Blood. 2018;132(Suppl 1):4161.

81.

Soumerai JD, Pagel JM, Jagadeesh D, Salman HS, Kenkre VP, Asch AS, et al. Initial results of a dose escalation study of a selective and structurally differentiated PI3Kδ inhibitor, ME-401, in relapsed/refractory (R/R) follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). J Clin Oncol. 2018;36(15_suppl):7519.CrossRef

82.

Harb WA, Diefenbach CS, Lakhani N, Rutherford SC, Schreeder MT, Ansell SM, et al. Phase 1 clinical safety, pharmacokinetics (PK), and activity of apilimod dimesylate (LAM-002A), a first-in-class inhibitor of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve), in patients with relapsed or refractory B-cell malignancies. Blood. 2017;130(Suppl 1):4119.

83.

Forero-Torres A, Rosen S, Smith DC, Lesser G, Peguero J, Gupta S, et al. Preliminary results from an ongoing phase 1/2 study of INCB057643, a bromodomain and extraterminal (BET) protein inhibitor, in patients (pts) with advanced malignancies. Blood. 2017;130(Suppl 1):4048.

84.

Querfeld C, Foss FM, Kim YH, Pinter-Brown L, William BM, Porcu P, et al. Phase 1 trial of cobomarsen, an inhibitor of Mir-155, in cutaneous T cell lymphoma. Blood. 2018;132(Suppl 1):2903.

85.

Maruyama D, Tobinai K, Makita S, Ishida T, Kusumoto S, Ishitsuka K, et al. First-in-human study of the EZH1/2 dual inhibitor DS-3201b in patients with relapsed or refractory non-Hodgkin lymphomas — preliminary results. Blood. 2017;130(Suppl 1):4070.

86.

Li L, Xiao S, Young KH, Zhang L, Li X, Fu X, et al. Efficacy and safety of novel targeted drug’ apatinib in relapse or refractory non-Hodgkin lymphoma: an open label, single-armed, exploratory study. Blood. 2017;130(Suppl 1):1548.

87.

Goodstal SM, Ma J, Lin J, Crandall T, Crowley L, Bender A, et al. M7583 is a highly selective and potent second generation BTK inhibitor for treatment of B-cell malignancies. Blood. 2017;130(Suppl 1):3845.

88.

Zelenetz AD, Soumerai JD, Jagadeesh D, Reddy N, Stathis A, Asch AS, et al. Preliminary safety and efficacy results with an intermittent schedule of the PI3kδ inhibitor ME-401 alone or in combination with rituximab for B-cell malignancies. Blood. 2018;132(Suppl 1):2893.

89.

Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017;129(13):1768–78.PubMedPubMedCentralCrossRef

Title: Novel and emerging therapies for B cell lymphoma
Authors: Sabarish Ayyappan
Kami Maddocks
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Lymphoma
Non-Hodgkin Lymphoma
Mantle Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Published in: Journal of Hematology & Oncology / Issue 1/2019
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-019-0752-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2019

Downregulation of CD73 associates with T cell exhaustion in AML patients

Incidence and death in 29 cancer groups in 2017 and trend analysis from 1990 to 2017 from the Global Burden of Disease Study

Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies

Burden of lymphoma in China, 2006–2016: an analysis of the Global Burden of Disease Study 2016

Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway

Strategies of adoptive T -cell transfer to treat refractory viral infections post allogeneic stem cell transplantation

Keynote webinar | Spotlight on antibody–drug conjugates in cancer