Immuno-Oncology and Multiple Myeloma

Multiple myeloma (MM) is at the forefront of immuno-oncology research, with a vast array of novel immunotherapies currently under investigation. Typical targets include plasma cell antigens, such as CD38 and SLAMF7, and immune checkpoints like PD-1, while immunotherapies targeting BCMA are showing promise.

Antibody-based approaches are reshaping the standard of care for MM. The addition of monoclonal antibodies to standard triplet regimens is proving efficacious; the addition of daratumumab to VMP has shown to be superior to VMP alone in the newly diagnosed setting1,2, while the addition of isatuximab, another anti-CD38 antibody, is looking promising in the frontline and relapsed/refractory settings3-5. Antibody-drug conjugates6-8 and bispecifics9,10 are also displaying potential. Other developments in this field include novel formulations, such as subcutaneous daratumumab, yielding improved convenience and safety11. Checkpoint inhibitor antibodies are an exciting therapy for MM, which are being tested in the frontline and relapsed/refractory settings. Pembrolizumab has produced positive results in both the upfront and relapsed settings12-14, while nivolumab, durvalumab and atezolizumab are also in trials15-17.

Another area of interest in immunotherapy for MM is CAR T-cell therapy. Promising agents include a SLAMF7-targeting CAR T-cell therapy18, and bb212119,20, which targets BCMA, and which many hope will follow in the steps of other CAR T-cell agents that have been approved for the treatment of ALL and DLBCL. NK-cell therapy21,22 and personalized vaccines23-25 are also being investigated, which while less established currently, are a promising area.

  1. Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2018 Feb 8; 378(6): 518-528.
  2. VJHemOnc.com [Internet]. Breaking news from the ALCYONE study of VMP plus daratumumab for NDMM; c2017-12; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/j6psevg57v8-breaking-news-from-the-alcyone-study-of-vmp-plus-daratumumab-for-ndmm/
  3. Richardson PG, Attal M, Campana F, et al. Isatuximab plus pomalidomide/dexamethasone versus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma: ICARIA Phase III study design. Future Oncol. 2018 May; 14(11): 1035-1047.
  4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2017 Oct 24. Identifier NCT03319667. Clinical Benefit of SAR650984, Bortezomib, Lenalidomide and Dexamethasone Combination in NDMM Patients Not Eligible for Transplant (IMROZ); [cited 2018 Sep 7]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03319667
  5. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2017 Sep 7. Identifier NCT03275285. Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients (IKEMA); [cited 2018 Sep 7]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03275285
  6. VJHemOnc.com [Internet]. Novel anti-BCMA immunotherapies have unprecedented responses; c2018-06; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/t-303y__zci-novel-anti-bcma-immunotherapies-have-unprecedented-responses/
  7. Lee L, Bounds D, Paterson J, et al. Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma. Br J Haematol. 2016 Sep; 174(6): 911-22.
  8. Sherbenou DW, Aftab BT, Su Y, et al. Antibody-drug conjugate targeting CD46 eliminates multiple myeloma cells. J Clin Invest. 2016 Dec 1; 126(12): 4640-4653.
  9. Seckinger A, Delgado JA, Moser S, et al. Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment. Cancer Cell. 2017 Mar 13; 31(3): 396-410.
  10. Hipp S, Tai YT, Blanset D, et al. A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo. Leukemia. 2017 Aug; 31(8): 1743-1751.
  11. VJHemOnc.com [Internet]. Subcutaneous daratumumab: combining efficacy, safety & convenience; c2018-06; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/qjguq157iek-subcutaneous-daratumumab-combining-efficacy-safety-convenience/
  12. VJHemOnc.com [Internet]. Immuno-oncology agents for MM: checkpoint inhibitors and NK-cells; c2018-06; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/0s_z8gxq3r8-immuno-oncology-agents-for-mm-checkpoint-inhibitors-and-nk-cells/
  13. Palumbo A, Mateos MV, San Miguel J, et al. KEYNOTE-185: a randomized, open-label phase 3 study of pembrolizumab in combination with lenalidomide and low-dose dexamethasone in newly diagnosed and treatment-naive multiple myeloma (MM). J Clin Oncol. 2018 June; 34(15).
  14. Shah JJ, Jagannath S, Mateos MV, et al. KEYNOTE-183: A randomized, open-label phase 3 study of pembrolizumab in combination with pomalidomide and low-dose dexamethasone in refractory or relapsed and refractory multiple myeloma (rrMM). J Clin Oncol. 2018 June; 34(15).
  15. Lonial S, Richardson P, Reece D, et al. CheckMate 602: A Phase 3, Open-Label, Randomized Trial of Combinations of Nivolumab, Elotuzumab, Pomalidomide, and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma. Blood. Sep 2017; 12(2); 330.
  16. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2015 Nov 30. Identifier NCT02616640. A Study to Determine Dose and Regimen of Durvalumab as Monotherapy or in Combination With Pomalidomide With or Without Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma; [cited 2018 Sep 7]. Available from: https://clinicaltrials.gov/ct2/show/NCT02616640
  17. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2015 April 30. Identifier NCT02431208. A Study of Atezolizumab (Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) Alone or in Combination With an Immunomodulatory Drug and/or Daratumumab in Participants With Multiple Myeloma (MM); [cited 2018 Sep 7]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02431208
  18. VJHemOnc.com [Internet]. New CAR T-cell targeting SLAMF7 shows efficacy against multiple myeloma; c2017-12; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/nyrbixeb0wy-new-car-t-cell-targeting-slamf7-shows-efficacy-against-multiple-myeloma/
  19. Berdeja JG, Lin Y, Raje N, et al. Durable Clinical Responses in Heavily Pretreated Patients with Relapsed/Refractory Multiple Myeloma: Updated Results from a Multicenter Study of bb2121 Anti-Bcma CAR T Cell Therapy. Blood. 2017; 130(1); 740.
  20. VJHemOnc.com [Internet]. Update on bb2121 CAR T-cell product for MM from EHA 2018; c2018-06; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/djz-jgug2mw-update-on-bb2121-car-t-cell-product-for-mm-from-eha-2018/
  21. VJHemOnc.com [Internet]. Promising results for MM treatment with natural killer cells; c2018-06; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/qakao7um7xg-promising-results-for-mm-treatment-with-natural-killer-cells/
  22. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2012 Nov 20. Identifier NCT01729091. Study of Umbilical Cord Blood-Derived Natural Killer Cells in Conjunction With Elotuzumab, Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant for Patients With Multiple Myeloma; [cited 2018 Aug 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT01729091
  23. VJHemOnc.com [Internet]. Personalized dendritic cell vaccine for acute leukemia and multiple myeloma; c2018-04; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/9zooz_nhvx8-personalized-dendritic-cell-vaccine-for-acute-leukemia-and-multiple-myeloma/
  24. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 Apr 5. Identifier NCT02728102. Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401); [cited 2018 Aug 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT02728102
  25. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2004 May 21. Identifier NCT00002787. Vaccine Therapy in Treating Patients With Multiple Myeloma Who Have Undergone Stem Cell Transplantation; [cited 2018 Aug 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT00002787
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