Efficacy and Safety of Ibrutinib as Monotherapy or Combination Therapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL): A Systematic Review and Meta-analysis.

Yin Li, Chunfan Li, Kebing Lv, Shixuan Wang, Fei Li
Author Information
  1. Yin Li: Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; and.
  2. Chunfan Li: Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; and.
  3. Kebing Lv: Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; and.
  4. Shixuan Wang: Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; and.
  5. Fei Li: Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; and.

Abstract

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease group. Ibrutinib's monotherapy or combination therapy is effective in relapsed/refractory (R/R) DLBCL. However, the treatment response in R/R DLBCL varies from 15% to 90% with different regimens, and the tolerance remains controversial.
AREAS OF UNCERTAINTY: The efficacy and safety of ibrutinib monotherapy or combination therapy in patients with R/R DLBCL remain uncertain.
DATA SOURCES: The PubMed, CBM, MEDLINE, Cochrane Library, and Embase databases were searched from their inception to July 2021.
THERAPEUTIC ADVANCES: The total complete remission rate (CRR) and overall response rate in R/R DLBCL patients treated with ibrutinib were 26% and 49%, respectively. The CRR of ibrutinib combination therapy was significantly higher than the ibrutinib monotherapy (45% vs. 19%). Moreover, the CRR of patients was 40% in double expressing lymphoma, 35% in central nervous system lymphoma, and 33% in nongerminal center B-cell-like (non-GCB) DLBCL, which was higher than the 8% in those with the GCB subtype. The pooled median PFS and overall survival were 5.57 and 10.17 months, respectively. GCB-DLBCL had the worst overall survival (5.1 months). Nevertheless, we found that combination regimens had no survival advantage compared with monotherapy (P > 0.05), indicating that combination therapy was only a transitional treatment and bridge for chimeric antigen receptor T cells or other treatments. Moreover, 12% of patients on ibrutinib combination therapy had ���grade 3 adverse events compared with 9% on ibrutinib monotherapy.
CONCLUSIONS: Ibrutinib monotherapy or combination therapy was safe and effective in treating R/R DLBCL with tolerable adverse reactions.

References

  1. Blood. 2017 Oct 19;130(16):1800-1808 [PMID: 28774879]
  2. Cancer Chemother Pharmacol. 2018 Apr;81(4):783-789 [PMID: 29476222]
  3. Semin Cancer Biol. 2013 Dec;23(6):410-21 [PMID: 24060900]
  4. Eur J Haematol. 2021 Sep;107(3):370-373 [PMID: 34018260]
  5. Br J Haematol. 2018 Sep;182(5):633-643 [PMID: 29808921]
  6. Blood. 2019 Sep 26;134(13):1024-1036 [PMID: 31331917]
  7. Blood. 2015 Jan 8;125(2):242-8 [PMID: 25355819]
  8. J Clin Oncol. 2020 Jan 10;38(2):155-165 [PMID: 31693429]
  9. J Clin Oncol. 2019 May 20;37(15):1285-1295 [PMID: 30901302]
  10. Oncotarget. 2019 May 14;10(35):3285-3293 [PMID: 31143374]
  11. Curr Oncol. 2019 Aug;26(4):253-265 [PMID: 31548805]
  12. Cancer Cell. 2017 Jun 12;31(6):833-843.e5 [PMID: 28552327]
  13. ANZ J Surg. 2003 Sep;73(9):712-6 [PMID: 12956787]
  14. N Engl J Med. 2018 Apr 12;378(15):1396-1407 [PMID: 29641966]
  15. Cancer Med. 2021 May;10(10):3214-3223 [PMID: 33932100]
  16. Neurology. 2017 Jan 3;88(1):101-102 [PMID: 27864520]
  17. N Engl J Med. 2019 Aug 1;381(5):432-443 [PMID: 31365801]
  18. Transl Oncol. 2021 Jan;14(1):100977 [PMID: 33395752]
  19. Cancer Discov. 2017 Sep;7(9):1018-1029 [PMID: 28619981]
  20. Lancet Oncol. 2019 Jan;20(1):31-42 [PMID: 30518502]
  21. Cancer Cell. 2021 Dec 13;39(12):1643-1653.e3 [PMID: 34739844]
  22. Am J Hematol. 2020 Jan;95(1):18-27 [PMID: 31621094]
  23. Nat Med. 2015 Aug;21(8):922-6 [PMID: 26193343]
  24. Am Soc Clin Oncol Educ Book. 2015;:e449-57 [PMID: 25993209]
  25. Blood Adv. 2019 Jan 22;3(2):132-135 [PMID: 30651281]
  26. Clin Lymphoma Myeloma Leuk. 2021 Mar;21(3):176-181 [PMID: 33358575]
  27. Lancet Haematol. 2019 Feb;6(2):e67-e78 [PMID: 30642819]
  28. Eur J Cancer. 2019 Aug;117:121-130 [PMID: 31279304]
  29. Blood Adv. 2019 Jun 11;3(11):1661-1669 [PMID: 31167818]
  30. Blood. 2019 Jan 31;133(5):436-445 [PMID: 30567753]
  31. Crit Rev Oncol Hematol. 2020 Aug;152:103010 [PMID: 32540781]
  32. Hematology Am Soc Hematol Educ Program. 2011;2011:498-505 [PMID: 22160081]
  33. Blood. 2017 Oct 5;130(14):1676-1679 [PMID: 28794071]
  34. Scand J Immunol. 2015 Sep;82(3):208-17 [PMID: 26111359]
  35. Ann Oncol. 2015 Sep;26 Suppl 5:v116-25 [PMID: 26314773]
  36. Blood. 2018 Apr 19;131(16):1805-1808 [PMID: 29386196]
  37. Ann Hematol. 2021 Jun;100(6):1509-1516 [PMID: 33900450]
  38. Pathology. 2018 Jan;50(1):74-87 [PMID: 29167021]

Grants

  1. 20212BCG74001/the Science and Technology Innovation Base Construction Project of Jiangxi Province
  2. 20213BCJ22016/the Program for Academic and Technical Leaders of Jiangxi Province
  3. No. 2024SSY06051/the Jiangxi Provincial Key Laboratory of Hematological Diseases

Word Cloud

Created with Highcharts 10.0.0DLBCLcombinationmonotherapytherapyR/RibrutinibpatientslymphomaCRRoverallsurvivalDiffuseB-celleffectivetreatmentresponseregimensraterespectivelyhigherMoreover5monthscomparedadverseIbrutinibBACKGROUND:largehighlyheterogeneousdiseasegroupIbrutinib'srelapsed/refractoryHowevervaries15%90%differenttoleranceremainscontroversialAREASOFUNCERTAINTY:efficacysafetyremainuncertainDATASOURCES:PubMedCBMMEDLINECochraneLibraryEmbasedatabasessearchedinceptionJuly2021THERAPEUTICADVANCES:totalcompleteremissiontreated26%49%significantly45%vs19%40%doubleexpressing35%centralnervoussystem33%nongerminalcenterB-cell-likenon-GCB8%GCBsubtypepooledmedianPFS571017GCB-DLBCLworst1NeverthelessfoundadvantageP>005indicatingtransitionalbridgechimericantigenreceptorTcellstreatments12%���grade3events9%CONCLUSIONS:safetreatingtolerablereactionsEfficacySafetyMonotherapyCombinationTherapyRelapsed/RefractoryLargeLymphoma:SystematicReviewMeta-analysis

Similar Articles

Cited By

No available data.