Lung cancer is the deadliest cancer in America today. While single-agent nivolumab—an anti-PD-1 checkpoint inhibitor—has been approved for non-small cell lung cancer (NSCLC), many patients still do not respond. Furthermore, there are no currently approved immunotherapies for patients with small-cell lung cancer (SCLC). Hopefully, based on new data presented Saturday at ASCO, these realities may improve in the near future.
First, Scott J. Antonia, M.D., Ph.D., of the H. Lee Moffitt Cancer Center, showed how the combination of the Bristol Myers-Squibb’s nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) checkpoint inhibitors was more effective in SCLC, and led to response rates that were nearly double those achieved with nivolumab alone. This work also involved Dung Le, M.D., with whom CRI is collaborating on a Fight Colorectal Cancer project, and importantly showed that these responses were both rapid and durable. Even patients who lacked expression of PD-L1, the counterpart to PD-1, were able to benefit from the combination, although patients with high PD-L1 were more likely to respond.
Antonia and Julie Brahmer, M.D., of the Johns Hopkins University School of Medicine, collaborated on work that revealed the superior effectiveness of this anti-PD-1 and anti-CTLA-4 combination in NSCLC patients, with response rates as high as 80%. As with SCLC, NSCLC patients also showed responses regardless of PD-L1 expression, though higher levels of PD-L1 did correlate with a higher chance of a successful outcome. This combination is also currently being evaluated in a phase 3 trial, the results of which could pave the way for its approval and allow it to be used to treat more patients.
Moving on to blood cancers, with the exception of bone marrow transplant, leukemia patients currently have no immunotherapies available to them outside the experimental setting. Earlier this month, nivolumab became the first and only immunotherapy approved for classical Hodgkin lymphoma (CHL) patients, but patients with non-Hodgkin lymphoma (NHL) still have no immunotherapy options. Fortunately, genetically modified, anti-CD19 CAR (chimeric antigen receptor) T cells, which we highlighted previously during AACR16, have shown an amazing ability to improve outcomes in both adult and child patients. Now, improved CAR T cell strategies show even greater promise for several patient populations.
Work by Stanley Riddell, M.D., of the Fred Hutchinson Cancer Research Center and a member of CRI’s Scientific Advisory Council, showcased a different approach to CAR T cells. While previous efforts have typically involved the use of CD8+ CAR T cells that can directly attack blood cancer cells, Riddell’s team used both killer CD8+ T cells as well helper CD4+ T cells. After first depleting patients’ native immune cells, infusions of this combination of CAR T cells enabled successful outcomes in several types of blood cancers. In this trial, incredibly high response rates of 94%, 91%, and 80% were achieved in patients with acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and NHL, respectively.
Finally, Jae Park, M.D., of Memorial Sloan Kettering Cancer Center, presented updated trial results on the use of another type of anti-CD19 CAR T cell. This CAR T cell has an added co-stimulatory domain, CD28, that promotes stronger anti-tumor activity. In adults with relapsed and refractory ALL, roughly 80% responded to treatment with these CAR T cells. While relapse is still an issue with CD19+ ALL, continued refinement of CAR T cell strategies, including identification and inclusion of the most effective co-stimulatory domains, appear to offer great potential for patients with all types of blood cancers.