Measurement challenges in immuno-oncology and novel therapies: Harmonising Toxicity and Response Assessment Across Immune Checkpoint Inhibitors, CAR-T, bispecific antibodies, and radioligand therapies

Background Immuno‑oncology therapies—including immune checkpoint inhibitors (ICIs), CAR T and other immune‑effector cell (IEC) therapies, bispecific antibodies (BsAbs), and radioligand therapies (RLTs)—have introduced complex toxicity and response phenomena that exceed traditional oncology measurement systems. Despite multiple society‑led frameworks, application across trials and real‑world care remains inconsistent, impairing comparability and patient safety. Methods We undertook a targeted narrative synthesis of major consensus guidelines and operational frameworks addressing irAEs, CRS/ICANS, BsAb toxicities, RLT monitoring, and immune-adapted response criteria. Content was organised across four domains: irAE measurement; modality-specific toxicity scales; delayed toxicities and data standards; and response interpretation. Expert input informed the practical integration of these frameworks. Results Four dominant measurement challenges emerged. (1) Inconsistent irAE capture: CTCAE remains the universal severity scale, yet application varies widely. Key omissions include diagnostic confirmation, steroid burden, timing, and rechallenge outcomes. Society algorithms (ASCO/ESMO/SITC) are insufficiently integrated into workflows, reducing reproducibility. (2) Inadequate scales for novel toxicities: CRS and ICANS from CAR T/IEC therapies require ASTCT grading, yet many centres still use legacy structures. BsAbs show distinct kinetics—recurrent, lower‑grade, step‑up‑related CRS—poorly captured without BsAb‑specific pathways. RLTs require dosimetry‑aware, procedure‑linked documentation absent from standard AE templates. (3) Under‑capture of delayed and chronic toxicities: Endocrine and cardiac irAEs frequently present late and persist, but most datasets lack survivorship fields, structured follow‑up modules, or multidisciplinary documentation. (4) Misclassification of treatment effect vs progression: Variable use of iRECIST, Lugano immunotherapy refinements, and iRANO/RANO 2.0 leads to premature discontinuation or inappropriate continuation of therapy, especially without mandated confirmation windows and clinical stability checks. A unified cross‑modality “common core” framework—integrating CTCAE‑anchored irAE capture, ASTCT CRS/ICANS grading, RLT procedural fields, and immune‑adapted response criteria—offers a practical solution to standardise measurement across settings. Conclusions A harmonised operational framework is essential to reduce fragmentation and support accurate, comparable immunotherapy assessment.