ASH18 Preview: Blood Cancer Immunotherapy Developments at 60th American Society of Hematology Meeting

This Saturday marks the first day of the American Society of Hematology's 60^th Annual Meeting (ASH18), which will take place December 1-4 in San Diego. During the four-day meeting, a variety of advances will be highlighted in blood cancers like leukemia, lymphoma, and myeloma.

In the past several years especially, immunotherapy has taken on a larger role in the treatment of patients with these blood cancers, most notably with the FDA’s approval of two chimeric antigen receptor (CAR) T cell therapies. Basic research has also played an important role in expanding our understanding of what enables these cancers to develop as well as how the immune system interacts with them throughout their development. Ultimately, this research helps to not only make existing treatments better, but also to uncover new avenues through which immunotherapy can be brought to bear against these cancers.

Over the next few days, a number of Cancer Research Institute (CRI) doctors and researchers will be showcasing their latest breakthroughs at ASH18. Among those CRI scientists who are leading work that will be featured in prominent talks at ASH18 are:

• Carl H. June, MD, of the University of Pennsylvania, whose team showed that durable responses in chronic lymphocytic leukemia (CLL) patients treated with CD19-targeting CAR T cell therapy were characterized by highly active CD8⁺ “killer” T cells during the early phase and a small number of persistent CD4⁺ “helper” T cells during the later phase. (Abstract 699)
• Markus Muschen, MD, PhD, of the City of Hope, who led projects that will be the focus of five separate talks: one which identified LGR5 as a biomarker of a crucial B cell receptor (BCR) binding event that initiates B cell acute lymphoblastic leukemia (B-ALL) and other B cell cancers, and may also serve as a promising target (Abstract 547); one which identified the IFITM3 surface receptor as a regulator of oncogenic activity via tyrosine kinase receptor (TRK) and Ras signaling in B cell cancers (Abstract 552); one which revealed that B-ALL clones often evolve to preferentially exploit a single dominant oncogenic pathway while silencing alternative oncogenic signaling pathways  (Abstract 568); one which showed that VpreB and Igll5 act as tumor suppressors in pre B-ALL cells, and that deleting VpreB often marks an early event in the development of B-ALL (Abstract 570); and one which determined that the CD25 receptor serves as a biomarker of oncogenic BCR signaling and a predictor of poor clinical outcome as well as a potential new target for immunotherapy (Abstract 776).
• Stanley R. Riddell, MD, of the Fred Hutchinson Cancer Research Center and the University of Washington, whose team showed that low doses of humanized, BCMA-targeting CAR T cells were safe and powerful in pre-treated patients with high risk multiple myeloma (Abstract 1011).
• Michel Sadelain, MD, PhD, of Memorial Sloan Kettering Cancer Center, whose team demonstrated that “armored” CAR T cells were effective at treating patients with either large cell lymphoma or CLL, without causing any cases of cytokine release syndrome (CRS) (Abstract 224).
• Marcel van den Brink, MD, PhD, of Memorial Sloan Kettering Cancer Center, who led projects that will be the focus of four separate talks: one which reported the novel role of GPR109a on donor T cells in the context of graft-versus-host-disease (GvHD) after bone marrow transplantation (BMT), showing that its deletion eliminated harmful GvHD (Abstract 61); one which demonstrated that high levels of  Enterococcus intestinal bacteria are associated with GvHD, and that a lactose-free diet can prevent their growth (Abstract 358); one which reported intestinal bacteria signatures, both before and after BMT, associated with chronic GvHD (Abstract 359); one which observed a correlation between lower bacterial diversity prior to BMT and a lower progression-free survival rate in multiple myeloma patients (Abstract 608); and one which showed that the prevalence of low diversity bacterial compositions extends across geographical boundaries and predicts poor overall survival  (Abstract 811).

Beyond those that led work being highlighted in ASH18 talks, CRI scientists also contributed to several other talks and either led or contributed to the many posters that will be presented this weekend:

• Iannis Aifantis, PhD, of the New York University School of Medicine, who is involved in work being highlighted in two talks (Abstracts 427 and 810).
• James P. Allison, PhD, and Padmanee Sharma, MD, PhD, both of the University of Texas MD Anderson Cancer Center, are involved in three talks (Abstracts 296, 905, and 906) and one poster (Abstract 4585). Dr. Sharma is also involved in one other talk (Abstract 483).
• Justin Guinney, PhD, of Sage Bionetworks, who led the work being highlighted in one poster (Abstract 2763).
• Carl H. June, MD, of the University of Pennsylvania, who is involved in five additional talks (Abstracts 197, 235, 298, 556, and 698), and involved in five posters (Abstracts 1886, 1973, 1974, 4198, and 4548).
• Markus Muschen, MD, PhD, of the City of Hope, who is involved in two additional talks (Abstracts 892 and 894), is the leader investigator of four posters (Abstracts 1336, 1373, 1587, and 3922), and involved in another two posters (Abstracts 1411 and 2857).
• Stanley R. Riddell, MD, of the Fred Hutchinson Cancer Research Center and the University of Washington, who is involved in two more talks (Abstracts 281 and 299), and is involved in three posters (Abstracts 1415, 1680, and 1681).
• Michel Sadelain, MD, PhD, of Memorial Sloan Kettering Cancer Center, who led one poster (Abstract 1412) and is involved in one additional poster (Abstract 4546).
• Mark John Smyth, PhD, of QIMR Berghofer, and Nicholas David Huntington, PhD, of the Walter and Eliza Hall Institute of Medical Research, are involved in one poster (Abstract 2031).
• Marcel van den Brink, MD, PhD, of Memorial Sloan Kettering Cancer Center, is the lead investigator on one poster (Abstract 3492) and is involved in four other posters (Abstracts 2078, 3167, 3342, and 3470).

Follow developments on Twitter with #ASH18.

Photo credit: Photo by Daniel Guerra on Unsplash.