Drug Response Profiling in pediatric ALL yields 68% objective responses and bridges to cellular therapies

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medRxiv Published April 16, 2026 Medically reviewed April 25, 2026 Study authors: Steffen, F. D.; Lissat, A.; Alten, J.; Kriston, A.; Scheidegger, N.; Eckert, C.; Bodmer, N.; Schori,… DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider Drug Response Profiling for individualized therapy in high-risk pediatric ALL, but interpret results cautiously due to observational data.

This prospective, multicenter Drug Response Profiling (DRP) registry enrolled 340 children with relapsed or refractory acute lymphoblastic leukemia across 17 European countries, with a median follow-up of 21 months (IQR: 14.7-26.6 months). The intervention involved DRP with image-based drug screening and functional testing, comparing venetoclax responders to non-responders, and included medications such as venetoclax, tyrosine kinase inhibitors, trametinib, bortezomib, and selinexor. Primary outcomes were objective clinical responses, with secondary outcomes including bridging to cellular therapies and event-survival.

Main results showed that 43 of 63 patients (68%) achieved objective clinical responses, with 42 patients bridged to cellular therapies, of whom 28 (67%) were still alive. For 1-year event-survival, top responders to venetoclax had a rate of 0.57 (95% CI, 0.39-0.85) compared to 0.25 (95% CI, 0.11-0.58), indicating superiority. Safety and tolerability data, including adverse events and discontinuations, were not reported.

Key limitations include the observational, non-randomized design, which precludes causal inferences, and potential lack of generalizability beyond this cohort. Funding and conflicts of interest were not reported. Practice relevance is that DRP may enable individualized therapy selection for enrollment in adaptive precision trials for high-risk pediatric ALL, but clinicians should note the evidence is associative and requires validation in controlled settings.

Study Details

Study typeCohort

Sample sizen = 340

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

Children with relapsed or refractory acute lymphoblastic leukemia (ALL) require more effective and less toxic therapies. We established a prospective, multicenter Drug Response Profiling (DRP) registry (NCT06550102) integrating functional testing into precision-guided treatment. DRP was performed for 340 patients from 17 European countries with a turn-around time of two-weeks. Image-based drug screening with over 135000 unique perturbations revealed a heterogeneous landscape of ex vivo responses to 88 drugs on average. Ranking drug responses across the patient cohort defined individual drug fingerprints, identifying "DRP twins" by similarity in sensitivity and resistance independent of genetic ALL subtypes. Of 239 high-risk patients with follow-up, DRP-informed interventions were reported for 63 patients (26%). Patients received combination therapies based on venetoclax, tyrosine kinase inhibitors, trametinib, bortezomib or selinexor, resulting in objective clinical responses in 43 cases (68%). Precision-guided treatments allowed bridging to cellular therapies in 42 patients among whom 28 (67%) were still alive with a median follow-up of 21 months after DRP (IQR: 14.7-26.6 months). Top responders to venetoclax, ranked within the first tertile of the cohort, had superior 1-year event-survival compared to venetoclax non-responders (0.57 [95% CI, 0.39-0.85] vs. 0.25 [95% CI, 0.11-0.58]). Collectively, these findings demonstrate the feasibility and clinical relevance of functional profiling within an international network. This scalable framework enables individualized therapy selection for enrolment in adaptive precision trials for high-risk pediatric ALL.