LOS ANGELES AACR IO 2025
At a recent oncology session from AACR Immunotherapy 2025, Melissa G. Lechner, MD, PhD, presented findings on the challenges of cancer immunotherapy. She focused on its autoimmune side effects and a newly identified link to bone health. The discussion highlighted the therapy’s expanding role and the need to address its risks as it reaches more patients.
The Growing Challenge of Immunotherapy Side Effects
Dr. Lechner began by framing the issue: “We had today was talking about immunotherapy and the autoimmune side effects that it can cause unhealthy tissues.” She noted that these effects are common, stating, “Side effects, which happen in about two/3s of patients,” affect roughly two-thirds of those treated. As immunotherapy moves from late-stage cancers like stage IV melanoma to earlier stages, she explained that tolerance for these risks varies. “I think the tolerance form of these side effects was different than the use in maybe earlier stage cancers now.”
Predicting Risk Through T-Cell Signatures
A key focus was identifying at-risk patients. “Can we identify who might be more likely to get these side effects?” Dr. Lechner asked. She pointed to research on T-cell signatures. At MD Anderson, Dr. Demetrio connected IL-17-producing Th17 cells to checkpoint inhibitor colitis. This finding, Dr. Lechner called “a really interesting profile” that might be managed with IL-6 blockers like tocilizumab. Other efforts, from the Crick Center and John Wherry’s group, explore broader immune profiling and tertiary lymphoid structures to predict toxicity.
Bone Density Concerns Linked to Anti-PD-1 Therapy
Dr. Lechner also shared a finding from Dr. Gwendolyn Joseph: “There was actually a decrease in bone mineral density in some animal models where they were treating with anti-PD-1 therapy.” Observed in aged mice, this could signal concerns for certain patients, such as those with breast cancer on checkpoint inhibitors. Options like bisphosphonates or denosumab were discussed. However, some may carry additional risks and benefits.
Emerging Alternatives to Steroid Treatment
On treatment, Dr. Lechner noted a shift beyond steroids. “Janus Kinus inhibitors, so a lot of the work that was presented today did identify T cells and signaling through stats.” These alternatives, already in use for other conditions, are gaining traction in updated guidelines.
A Call for Comprehensive Research and Trials
Looking ahead, Dr. Lechner emphasized comprehensive data collection. “We really have to take a broad look, whether it’s getting a good detailed history on the patient’s autoimmune history, looking at their genetic background, and then also getting blood samples and data sets to look for these specific phenotypes.” She advocated for prospective studies to refine immunotherapy’s safety profile.
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