Immuno-Oncology (I-O) Focus

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

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 setting^1,2, while the addition of isatuximab, another anti-CD38 antibody, is looking promising in the frontline and relapsed/refractory settings^3-5. Antibody-drug conjugates^6-8and bispecifics^9,10 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 settings^12-14, while nivolumab, durvalumab and atezolizumab are also in trials^15-17.

Another area of interest in immunotherapy for MM is CAR T-cell therapy. Promising agents include a SLAMF7-targeting CAR T-cell therapy¹⁸, and bb2121^19,20, 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 therapy^21,22 and personalized vaccines^23-25are also being investigated, which while less established currently, are a promising area.

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.
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/
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.
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
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
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/
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.
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.
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.
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.
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/
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/
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).
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).
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.
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
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
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/
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.
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/
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/
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
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/
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
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