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.

Chronic lymphocytic leukemia (CLL) is known to cause impaired immune responses, which combined with the fact it often effects older patients who are more likely to be unfit for traditional therapies, makes CLL an ideal disease for immunotherapy¹.

The inclusion of the anti-CD20 monoclonal antibody rituximab into chemotherapy regimens was a paradigm-changing move in CLL treatment², while ofatumumab³ and obinutzumab^4-6, which also target CD20, are also valuable additions to the arsenal against CLL. Bispecific antibodies, such as blinatumomab, are another interesting area of investigation⁷.

Combining immune checkpoint inhibitors with other novel agents is proving to be a promising therapeutic strategy for CLL. Exciting response rates were observed with the PD-1 inhibitor pembrolizumab, the anti-CD20 antibody ublituximab and the PI3K-δ inhibitor umbralisib in the relapsed setting⁸. The combination of pembrolizumab with idelalisib or ibrutinib is also under investigation for relapsed CLL⁹. For Richter’s transformation, nivolumab combinations are also proving hopeful^10,11.

CAR T-cell therapy is a hot topic of investigation, with several agents already approved in other hematological malignancies. In CLL this area is not seeing the same responses as ALL and DLBCL yet, but holds promise for the future^12-15.

Freeman CL & Gribben JG. Immunotherapy in Chronic Lymphocytic Leukaemia (CLL). Curr Hematol Malig Rep. 2016; 11: 29-36.
Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010 Oct 2; 376(9747): 1164-74.
Hillmen P, Robak T, Janssens A, et al. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015 May 9; 385(9980): 1873-83.
Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20; 370(12): 1101-10.
VJHemOnc.com [Internet]. Obinutuzumab increases survival in CLL patients with comorbidities; c2018-06; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/hnls7ipero8-obinutuzumab-increases-survival-in-cll-patients-with-comorbidities/
VJHemOnc.com [Internet]. CLL11 trial shows improved OS rates in CLL with obinutuzumab; c2018-06; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/rhbash6dwky-cll11-trial-shows-improved-os-rates-in-cll-with-obinutuzumab/
Robinson HR, Qi J, Cook EM, et al. A CD19/CD3 bispecific antibody for effective immunotherapy of chronic lymphocytic leukemia in the ibrutinib era. Blood. 2018 Aug 2; 132(5): 521-532.
VJHemOnc.com [Internet]. Triple therapy for CLL: pembrolizumab, ublituximab and umbralisib; c2017-12; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/btiembhzimg-triple-therapy-for-cll-pembrolizumab-ublituximab-and-umbralisib/
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2015 Jan 7. Identifier NCT02332980. Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas; [cited 2018 Sep 7]. Available from: https://clinicaltrials.gov/ct2/show/NCT02332980
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2015 Apr 20. Identifier NCT02420912. Nivolumab With Ibrutinib for Relapsed, Refractory or High-Risk Untreated Patients With Chronic Lymphocytic Leukemia (CLL); [cited 2018 Sep 7]. Available from: https://clinicaltrials.gov/ct2/show/NCT02420912
VJHemOnc.com [Internet]. Strategies for treating Richter’s transformation in CLL: checkpoint inhibitors and venetoclax; c2017-12; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/k9armct2ppo-strategies-for-treating-richters-transformation-in-cll-checkpoint-inhibitors-and-venetoclax/
Mato A & Porter DL. A drive through cellular therapy for CLL in 2015: allogeneic cell transplantation and CARs. Blood. 2015 Jul 23; 126(4): 478-85.
VJHemOnc.com [Internet]. CAR T-cells for CLL: ibrutinib pre-treatment, T-cell quality and future predictions; c2017-12; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/mnjp84pyqdc-car-t-cells-for-cll-ibrutinib-pre-treatment-t-cell-quality-and-future-predictions/
VJHemOnc.com [Internet]. Response to CAR T-cell treatment in CLL patients; c2018-04; [cited 2018 Sep 7]. Available from: https://www.vjhemonc.com/video/xx6t4khml0-response-to-car-t-cell-treatment-in-cll-patients/
Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015 Sep 2; 7(303).