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.

Checkpoint inhibitors cause block key immune checkpoints. These checkpoints can be stimulatory or inhibitory; blocking inhibitory checkpoints can restore immune function¹. Many immune checkpoints are stimulated by ligand-receptor interactions, which can be blocked using antibodies^1,2. Current targets of immune checkpoint inhibitor agents include: CTLA-4, which is targeted by ipilimumab³; PD-1, the target of nivolumab⁴ and pembrolizumab⁵; and PD-L1, a target of durvalumab⁶. Many more potential targets are being research, including LAG3⁷, CD137⁸ and CD27⁹.

Immune-related adverse events can be associated with immune checkpoint blockade – these are typically organ-specific, including colitis and nephritis^10,11. However, checkpoint inhibitors avoid many of the side effects of cytotoxic therapies, making them excellent partners for combination regimens¹¹. One promising combination strategy is using PD-1 inhibitors with the hypomethylating agent azacytidine to boost response^2,12-14.

An array of benefits are provided by immune checkpoint inhibitors, with good overall response rates^15,16. However, only a subset of patients respond; therefore, it is crucial to develop predictive markers to determine which patients will respond to this therapy^17,18.

Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Apr; 12(4): 252–264.
VJHemOnc.com [Internet]. Immune checkpoint inhibitors for AML: mechanism, rationale & using azacitidine to boost response; c2018-02; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/hpb1x3518ps-immune-checkpoint-inhibitors-for-aml-mechanism-rationale-using-azacitidine-to-boost-response/
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2012 Dec 31. Identifier NCT01757639. Ipilimumab in Treating Patients With Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT01757639
VJHemOnc.com [Internet]. Checkmate 205 study results: nivolumab in classical Hodgkin Lymphoma; c2018-04; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/2mpqn6k9lyc-checkmate-205-study-results-nivolumab-in-classical-hodgkin-lymphoma/
VJHemOnc.com [Internet]. Immuno-oncology agents for MM: checkpoint inhibitors and NK-cells; c2018-06; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/0s_z8gxq3r8-immuno-oncology-agents-for-mm-checkpoint-inhibitors-and-nk-cells/
VJHemOnc.com [Internet]. Immune checkpoint inhibitors and their role in MM: pembrolizumab and durvalumab; c2017-06; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/b9r09suuob8-immune-checkpoint-inhibitors-and-their-role-in-mm-pembrolizumab-and-durvalumab/
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2014 Feb 13. Identifier NCT02061761. Safety Study of Anti-LAG-3 in Relapsed or Refractory Hematologic Malignancies; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02061761
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2013 Jan 25. Identifier NCT01775631. Combination Study of Urelumab and Rituximab in Patients With B-cell Non-Hodgkins Lymphoma; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT01775631
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2011 Oct 26. Identifier NCT01460134. A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT01775631
Postow MA, Sidlow R & Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018 Jan 11; 378(2): 158-168.
VJHemOnc.com [Internet]. Checkpoint inhibitors: parallel management of the disease and immune-related toxicities; c2018-02; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/r2wev3vzwjy-checkpoint-inhibitors-parallel-management-of-the-disease-and-immune-related-toxicities/
VJHemOnc.com [Internet]. Update on checkpoint inhibitor therapy for AML: salvage, frontline & azacitidine combination; c2018-02; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/ynszmeo0v3e-update-on-checkpoint-inhibitor-therapy-for-aml-salvage-frontline-azacitidine-combination/
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2015 Mar 25. Identifier NCT02397720. An Open-Label Phase II Study of Nivolumab (BMS-936558) in Combination With 5-azacytidine (Vidaza) or Nivolumab With Ipilimumab in Combination With 5-azacytidine for the Treatment of Patients With Refractory/ Relapsed Acute Myeloid Leukemia and Newly Diagnosed Older AML (>65 Years) Patients; [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02397720
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 May 18. Identifier NCT02775903. An Efficacy and Safety Study of Azacitidine Subcutaneous in Combination With Durvalumab (MEDI4736) in Previously Untreated Subjects With Higher-Risk Myelodysplastic Syndromes (MDS) or in Elderly Subjects With Acute Myeloid Leukemia (AML); [cited 2018 Aug 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02775903
Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015 Dec; 372(4): 311–9.
Younes A, Santoro A, Shipp M, et al. Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplant and brentuximab vedotin: a multicentre, single-arm phase 2 trial. Lancet Oncol. 2016 Sep; 17(9): 1283–94.
VJHemOnc.com [Internet]. Predict response to immune checkpoint inhibition in acute myeloid leukemia (AML) using biomarkers; c2017-02; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/a155l6bzadw-predict-response-to-immune-checkpoint-inhibition-in-acute-myeloid-leukemia-aml-using-biomarkers/
VJHemOnc.com [Internet]. Identifying predictive factors of outcome in elderly lymphoma; c2018-06; [cited 2018 Aug 23]. Available from: https://www.vjhemonc.com/video/3huvnlr5do4-identifying-predictive-factors-of-outcome-in-elderly-lymphoma/