Why Current Questionnaires Miss What CAR-T and Bispecific Antibody Patients Really Feel

Revolutionary immunotherapies are transforming survival for people with blood cancers, but the questionnaires designed to capture what those patients actually experience are lagging dangerously behind the treatments themselves. A sweeping multi-stakeholder study published in Frontiers in Hematology has revealed that patient-reported outcome measures, or PROMs, used in trials of CAR-T cell therapy and bispecific antibodies are failing to capture the full spectrum of side effects, emotional strain, and life disruption that these novel treatments inflict. The findings expose a critical blind spot in how the medical community evaluates the world’s most expensive cancer therapies.

The research team, led by Eilidh M. Duncan of Myeloma Patients Europe in Brussels, brought together an unusually diverse group of 38 participants to tackle the problem. Rather than consulting only clinicians or researchers, the investigators recruited patients with direct experience of CAR-T or bispecific antibody treatment, informal family carers, patient advocates from myeloma, lymphoma, and leukaemia communities, academic researchers, trialists, pharmaceutical industry representatives, and officials from regulatory and health technology assessment bodies, including the FDA and EMA. Data came from 14 one-to-one interviews with 16 participants and two online focus groups involving 15 and 19 participants respectively. Transcripts were analysed using a deductive-inductive thematic approach with double coding by independent researchers, a methodological rigor that strengthens the credibility of the resulting themes.

The technical context makes the challenge clear. CAR-T therapy involves engineering a patient’s own T cells to recognise cancer cells, while bispecific antibodies, or BsAbs, are laboratory-made molecules that physically link T cells to malignant cells. Both can trigger cytokine release syndrome, an immune overreaction causing fever, nausea, headache, low blood pressure, and potentially multi-organ failure. They can also cause immune effector cell-associated neurotoxicity syndrome, or ICANS, a neuropsychiatric condition ranging from mild tremor and confusion to haemorrhage, coma, and death. According to the study, CRS occurs in roughly 87 percent of CAR-T patients and 67 percent of those receiving BsAbs, while neurotoxicity affects 40 to 64 percent of CAR-T recipients, with 27 percent requiring intensive care admission. These acute toxicities typically emerge within one to four weeks after treatment, yet longer-term experiences are rarely assessed or reported.

One of the most striking findings concerns the logistical maze surrounding CAR-T treatment. Because the therapy is only available at specialised centres, patients frequently travel more than 100 kilometres for infusion and hospitalisation, then return to local providers for follow-up. This fragmentation across multiple treatment sites complicates PROM data capture and contributes to missing data. Participants also highlighted a sobering measurement paradox: patients experiencing the worst toxicities, such as cognitive impairment from ICANS or severe CRS, are often too unwell to complete questionnaires at all. As one researcher explained, the data dip between pre-lymphodepletion and week two captures only the sick patients who are still fit enough to fill out forms, not the sickest ones, making the reasons for missing data critically important to understand.

Bispecific antibodies present their own distinct measurement headache. Unlike CAR-T, which is a fixed-duration treatment, BsAbs involve continuous administration with a wide variety of side effects occurring over different time periods. Participants described agents such as talquetamab, a GPRC5D-targeting bispecific, which produces gastrointestinal effects, skin toxicity, complete taste loss, falling nails, itchy rashes, and weight loss. Some symptoms resolve over several months while others, like taste changes and weight loss, persist indefinitely. These treatment-specific domains fall outside the scope of generic instruments such as the EORTC QLQ-C30, which was designed for broad applicability rather than therapy-specific sensitivity. A recent review found 15 distinct PROMs used within just 16 CAR-T studies, highlighting the heterogeneity that undermines evidence synthesis across trials.

The timing of assessments emerged as a central controversy. Participants broadly agreed that baseline measurements for CAR-T and BsAbs trials should occur earlier than for older anticancer therapies, yet uncertainty persists about what baseline actually means. Because the CAR-T process spans several weeks, including leukapheresis, bridging therapies, and hospitalisation, a patient’s disease status and quality of life can shift dramatically between initial stages and infusion. Several researchers argued that future analyses should include two baselines, one right before lymphodepletion and one at the time of apheresis. Health technology assessment representatives insisted that baseline should mean study baseline, tied to treatment decision or randomisation, not any later time point.

Follow-up timing proved equally contentious. Participants suggested assessments as early as one week after infusion could serve as a crucial anchor point to capture the frequency, intensity, severity, and resolution of side effects. Industry representatives acknowledged the feasibility challenges, noting that patients are often hospitalised and facing severe complications like CRS shortly after infusion. For BsAbs with step-up dosing, where patients receive three doses during week one, some argued quality of life and toxicity should be explored after each individual dose. A regulatory representative called for weekly assessments during the first two months after CAR-T administration, using an item library to select really important symptoms such as headache and fatigue, alongside physical functioning measured on a high-frequency basis.

Perhaps the most emotionally resonant finding concerns what current PROMs systematically miss. Patients described the intense mental strain of waiting for CAR-T, including fear that their health would deteriorate during the manufacturing interval and render them ineligible. One patient recounted that doctors and nurses focused on physical side effects while never asking about the mental part, which was the most difficult aspect, and that her doctor essentially told her the mental part was hers to handle alone. Participants also flagged emerging concepts like time toxicity, meaning the time patients spend managing treatment and its effects, along with the burden on family carers, financial strain, and the psychological weight of living with an immunocompromised state. None of the three commonly used PROMs in trials, the EORTC QLQ-C30, MDASI-CAR, and PRO-CTCAE, capture waiting anxiety, logistical burden, caregiver burden, or treatment-free survival.

The study’s recommendations form a concrete blueprint for reform. The authors propose a dual-baseline strategy appropriate for rapid clinical changes preceding CAR-T infusion, mandated early high-frequency assessments, meaning weekly for the first four weeks, systematic inclusion of patient-important domains currently under-captured such as emotional well-being and time toxicity, continued PRO data collection beyond clinical progression, and transparent, comprehensive reporting of PRO findings. They also endorse interim strategies like combining instruments, adding PRO-CTCAE items to primary measures, and incorporating qualitative interviews or free-text responses. Longer-term, they support developing new treatment-specific PROMs, potentially with a modular core-plus-supplement design, alongside computerised adaptive testing to tailor questionnaires to individuals and reduce respondent burden.

The stakes extend far beyond academic measurement. CAR-T and BsAbs are high-cost therapies whose cost-effectiveness for health systems remains controversial, and PROM data directly informs reimbursement decisions. Under-reporting PRO data, the authors argue, is not just a concern for research validity but an unethical waste of patients’ time and energy, breaking the implicit agreement that patients’ contributions will meaningfully inform knowledge generation. Patients were willing to complete PROMs when they understood how their data would be used and felt confident it would not be wasted. As these immunotherapies continue to expand across haematological malignancies, the gap between what patients endure and what trials record can no longer be ignored. Clearer guidance from regulators and payers on instrument selection, assessment schedules, and reporting would substantially improve the quality and patient-centredness of evidence in this rapidly evolving field.

Subject of Research: Optimisation of patient-reported outcome measures for haematological cancer patients receiving CAR-T and bispecific antibody immunotherapies

Article Title: Optimisation of patient-reported outcome measurement for haematological cancer patients receiving novel immunotherapies: perspectives of multi-stakeholders

Article References: Duncan, E. M., Salviano, J., Kyriakou, C., Nier, S., Oerlemans, S., Salek, S., Morgan, K., & Joyner, K. (2026). Optimisation of patient-reported outcome measurement for haematological cancer patients receiving novel immunotherapies: perspectives of multi-stakeholders. Frontiers in Hematology, 5, Article 1800304. https://doi.org/10.3389/frhem.2026.1800304

Image Credits: AI Generated

DOI: 10.3389/frhem.2026.1800304

Keywords: CAR-T therapy, bispecific antibodies, patient-reported outcomes, PROMs, haematological malignancies, cytokine release syndrome, ICANS, quality of life, clinical trials, time toxicity, regulatory guidance, survivorship