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Immuno-Oncology and Antibodies

The Immuno-oncology (I-O) Focus on VJHemOnc is supported by Johnson & Johnson. This supporter has no influence over the production of the content.

Since the first new humanized monoclonal antibody treatments were developed, agents like rituximab have become a mainstay of treatment regimens for a range of hematological pathologies. These are classically directed against single antigens overexpressed on malignant cells, such as CD20. Target antigens for antibody treatments for use in hematological malignancies now include, among others, CD331, CD382, SLAMF73, CTLA-44, PD-L15 and BCMA6.

Next-generation antibody therapies offer the potential of further improving treatment. These novel strategies include bispecific, dual affinity antibodies7-9, immune checkpoint inhibitors5,10,11, and antibody-drug conjugates12,13. In addition to their utility as monotherapies14, these antibodies provide a large number of potential combinations for trials with other immunotherapies, targeted small molecules and chemotherapy15-18.

Biomarkers to predict response to these antibody treatments are an exciting area of research, which could help select responders, thus improving patient outcomes19. In addition, the infusion-related toxicities of certain antibody treatments, such as daratumumab, can be reduced through the development of subcutaneous formulations20,21. Other developments in the field include the release of biosimilar antibodies following the expiry of patents on branded agents; these can greatly reduce the cost of treatment, although strict regulation and data on equivalence is required22-24.

  1. Laszlo GS, Gudgeon CJ, Harrington KH, et al. Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML. Blood. 2014 Jan 23; 123(4): 554-61.
  2. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 Nov 9. Identifier NCT02960555. Trial of Isatuximab (SAR650984) in Patients With High Risk Smoldering Multiple Myeloma; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02960555
  3. FDA.gov [Internet]. FDA approves Empliciti, a new immune-stimulating therapy to treat multiple myeloma; c2015-11 [updated 2015 Nov 30]; [cited 2018 Aug 23]. Available from: https://wayback.archive-it.org/7993/20180125101440/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm474684.htm
  4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2012 Nov 20. Identifier NCT01729806. Ipilimumab and Rituximab in Treating Patients With Relapsed or Refractory B-cell Lymphoma; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT01729806
  5. VJHemOnc.com [Internet]. Immune checkpoint inhibitors and their role in MM: pembrolizumab and durvalumab; c2018-06; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/b9r09suuob8-immune-checkpoint-inhibitors-and-their-role-in-mm-pembrolizumab-and-durvalumab/
  6. VJHemOnc.com [Internet]. Novel anti-BCMA immunotherapies have unprecedented responses; c2018-06; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/t-303y__zci-novel-anti-bcma-immunotherapies-have-unprecedented-responses/
  7. FDA.gov [Internet]. FDA grants regular approval to blinatumomab and expands indication to include Philadelphia chromosome-positive B cell; c2017-07 [updated 2017 Jul 12]; [cited 2018 Aug 23]. Available from: https://wayback.archive-it.org/7993/20170722151121/https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm566708.htm
  8. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2015 Aug 11. Identifier NCT02520427. A Phase 1 Study of AMG 330 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02520427
  9. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2014 June 2. Identifier NCT02152956. Safety Study of MGD006 in Relapsed/Refractory Acute Myeloid Leukemia (AML) or Intermediate-2/High Risk MDS; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02152956
  10. FDA.gov [Internet]. Pembrolizumab (KEYTRUDA) for classical Hodgkin lymphoma; c2017-03 [updated 2017 Mar 15]; [cited 2018 Aug 23]. Available from: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm546893.htm
  11. FDA.gov [Internet]. Nivolumab (Opdivo) for Hodgkin Lymphoma; c2016-05 [updated 2016 May 17]; [cited 2018 Aug 23]. Available from: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm501412.htm
  12. VJHemOnc.com [Internet]. A breakthrough therapy: polatuzumab vedotin plus BR for R/R DLBCL; c2018-06; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/couxpr8urtw-a-breakthrough-therapy-polatuzumab-vedotin-plus-br-for-rr-dlbcl/
  13. VJHemOnc.com [Internet]. Gemtuzumab ozogamicin for AML: challenges and reapproval; c2018-05; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/wbigqrz1rhy-gemtuzumab-ozogamicin-for-aml-challenges-and-reapproval/
  14. VJHemOnc.com [Internet]. CENTAURUS trial: daratumumab monotherapy for smoldering multiple myeloma; c2017-12; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/stpdduqg0yw-centaurus-trial-daratumumab-monotherapy-for-smoldering-multiple-myeloma/
  15. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2015 Jan 7. Identifier NCT02332850. SAR650984 in Combination With Carfilzomib for Treatment of Relapsed or Refractory Multiple Myeloma; [cited 2018 Aug 23]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02332850
  16. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2011 Nov 22. Identifier NCT01476787. Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma (RELEVANCE); [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT01476787
  17. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2014 Oct 6. Identifier NCT02257567. A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02257567
  18. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2013 Dec 3. Identifier NCT01998971. A Study of JNJ-54767414 (HuMax CD38) (Anti-CD38 Monoclonal Antibody) in Combination With Backbone Treatments for the Treatment of Patients With Multiple Myeloma; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT01998971
  19. VJHemOnc.com [Internet]. Advances in predictive biomarkers for immuno-oncology agents; c2018-06; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/yhopksxhpcm-advances-in-predictive-biomarkers-for-immuno-oncology-agents/
  20. VJHemOnc.com [Internet]. Subcutaneous daratumumab: an update on the latest MM clinical trials; c2018-06; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/38kkjimfpba-subcutaneous-daratumumab-an-update-on-the-latest-mm-clinical-trials/
  21. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2015 Aug 11. Identifier NCT02519452. A Study of Daratumumab With the Addition of Recombinant Human Hyaluronidase (rHuPH20) for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02519452
  22. VJHemOnc.com [Internet]. How will biosimilars save us money?; c2017-03; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/_go7gyktaf0-how-will-biosimilars-save-us-money/
  23. VJHemOnc.com [Internet]. Practical intricacies surrounding biosimilar adoption; c2017-10; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/a8rjcngm8sm-practical-intricacies-surrounding-biosimilar-adoption/
  24. Weise M, Kurki P, Wolff-Holz E, et al. Biosimilars: the science of extrapolation. Blood. 2014 Nov 20; 124(22): 3191-6.
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