The Way Ahead: The Convergence of Technology and Cancer Care, May 2024 Edition

Updates on Cellular Therapy and Roles of AI in Clinical Practice

AI in Clinical Practice: A study published last month in The New England Journal of Medicine (NEJM) Artificial Intelligence (AI) evaluated five large language models (LLMs) in clinical oncology, focusing on their ability to handle 2,044 oncology-related questions ranging from radiation oncology to cancer biology. The models tested included LLaMA 1, PaLM 2, Claude-v1, GPT-3.5, and GPT-4.

GPT-4 emerged as the top performer, surpassing the 50th percentile compared to human benchmarks. However, all models displayed variability in performance, struggling the most with clinical oncology subcategories and female-predominant malignancies. Strategies such as model selection, prompt repetition, and self-appraised confidence scoring helped identify high-performing subgroups, with accuracy rates around 81% for Claude-v1 and GPT-4. Despite advancements in LLMs, significant error rates and overconfidence are key challenges, underscoring the need for safe integration of AI into routine clinical practice.

Another LLM study recently published in Lancet Digital Health utilized GPT-4 (in comparison to six radiation oncology attendings) to respond to 100 scenario and symptom questions for patients with cancer. GPT-4’s responses posed severe harm risks in 7.1% of responses and a mortality risk in 0.6%, mainly due to misjudging the acuity of scenarios. LLM-assisted responses improved inter-physician agreement compared to manual responses. While LLM drafts were less likely to include direct clinical actions, they provided more educational content and self-management advice. The average LLM response (169 words) and LLM-assisted response (160 words) was much longer than the manual response (34 words). LLMs can certainly reduce physician workload and enhance response quality, but responses must be carefully monitored for patient safety and to avoid automation bias.

Cellular Therapy Update: The FDA has mandated updated boxed warnings for all approved chimeric antigen receptor (CAR) T-cell therapies to highlight the serious risk of T-cell malignancies. The FDA’s safety labeling changes, initiated in January 2024, followed reports from clinical trials and post-marketing data. Updates to warnings, precautions, post-marketing experience, and patient counseling information are also required. Patients and trial participants receiving CAR T-cell therapy must receive lifelong monitoring for secondary malignancies, and manufacturers should be contacted in the event of new malignancies.

This particularly affects BCMA- and CD19-directed CAR T-cell products, including idecabtagene vicleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel, tisagenlecleucel, brexucabtagene autoleucel, and axicabtagene ciloleucel. In the linked article in Blood Advances, Dr. Rahul Banerjee, Oncology Data Advisor Editor in Chief and Assistant Professor of Medicine at the University of Washington, Fred Hutchinson Cancer Center, notes that this risk can be mitigated if CAR T is used earlier in the treatment course and suggests that the overall benefits outweigh its harms. Despite the FDA’s recent mandate, advancements in the field carry on.

Bristol Myers Squibb’s Breyanzi® (lisocabtagene maraleucel) received accelerated approval to treat relapsed or refractory follicular lymphoma (FL) after at least two prior therapies, joining Gilead Sciences’ Yescarta® (axicabtagene ciloleucel)and Novartis’ Kymriah® (tisagenlecleucel) in the FL landscape. Lisocabtagene maraleucel’s approval was based on impressive results from its phase 2 TRANSCEND FL trial, with a 95.7% tumor response rate and a 73.4% complete response rate. Despite slightly lower complete response rates compared to earlier data, 77.1% of responders are still in remission at 18 months. As lisocabtagene maraleucel expands in its number of indications (including chronic lymphocytic leukemia and small lymphocytic lymphoma), expanding access to community practices and building designated treatment centers will just as pivotal.

About Dr. Haque

Waqas Haque, MD, MPH, is a third-year Internal Medicine Resident at New York University (NYU) in a Clinical Investigator Track. He recently matched to the University of Chicago for fellowship, which he will be beginning later in 2024. As a Clinical Investigator Track Resident, Dr. Haque has balanced his patient care work with a variety of research projects. During his fellowship training at the University of Chicago, he plans to further his work in innovative clinical trial design, value-based care delivery to cancer patients, and clinical investigation.

For More Information

Rydzewski NR, Dinakaran D, Zhao SG, et al (2024). Comparative evaluation of LLMs in clinical oncology. N Engl J Med AI, 1(5). DOI:10.1056/AIoa2300151

Chen S, Guevara M, Moningi S, et al (2024). The effect of using a large language model to respond to patient messages. Lancet Digital Health, 6(6):E379-E381. DOI:10.1016/S2589-7500(24)00060-8

US Food & Drug Administration (2024). FDA requires boxed warning for T cell malignancies following treatment with BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. Available at: https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed

Banerjee R, Poh C, Hirayama AV, et al (2024). Answering the “Doctor, can CAR-T therapy cause cancer?” question in clinic. Blood Adv, 8(4):895-898. DOI:10.1182/bloodadvances.2023012336

US Food & Drug Administration (2024). FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma

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