Yee, Claire

Abstract Background This secondary analysis of a phase I clinical trial illustrates integrated summary and visualization of Common Terminology Criteria for Adverse Events (CTCAE) data and Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE) data at baseline and through the first cycle of treatment for tolerability review during dose-cohort evaluation in a phase I trial. Methods This study uses data from a phase I clinical trial of patients with relapsed or refractory acute myeloid leukemia. Through iterative feedback from clinicians and statisticians, we developed a summary of cycle 1 PRO-CTCAE and CTCAE data for the first dose-level cohort. This summary is intended to demonstrate reporting that would be reviewed to inform a decision about proceeding to the next dose level in a dose escalation trial. Results Cycle 1 CTCAE and PRO-CTCAE data for 4 patients enrolled in the first dose cohort are summarized as narrative and tabular summaries and visualized using swimmer and butterfly plots. In this cohort, 3/4 (75%) patients had at least one CTCAE grade 3 or higher adverse event, and all 4 (100%) patients had at least one PRO-CTCAE composite score of 3 during cycle 1. All 4 (100%) patients had at least one symptom for which PRO-CTCAE suggested greater symptom burden than was reflected in CTCAE. Conclusions In this illustrative summary of a dose cohort, PRO-CTCAE complemented CTCAE reporting by capturing patient-reported symptomatic burden that was not always fully reflected by clinician-graded adverse events. Reviewing PRO-CTCAE and CTCAE data together during dose-cohort evaluation may enrich discussions on safety and tolerability in phase I trials.

TPS2103 Background: Treatment for newly diagnosed IDH-mutant astrocytoma, WHO grade 3, is based on the results of the CATNON study, demonstrating benefit of radiotherapy followed by 12 months of adjuvant temozolomide. While temozolomide and radiotherapy significantly improved survival, the prognosis for these patients remains limited and more effective therapies are required. This trial will evaluate the benefit of the addition of the IDH1 and IDH-2 inhibitor vorasidenib to adjuvant temozolomide versus placebo following standard radiotherapy to evaluate possible improvement in outcomes. Methods: Alliance A072301 (NCT07215910) is a multicenter, double-blinded phase 3 randomized study to determine if the addition of vorasidenib to adjuvant temozolomide significantly improves progression-free survival (PFS), based on blinded central review in patients with newly diagnosed, IDH-mutant astrocytoma, WHO grade 3. Key inclusion criteria include age ≥ 12 years old, histological confirmation of astrocytoma (absence of 1p/19q codeletion), WHO grade 3, presence of any IDH mutation, plan for radiation and chemotherapy and surgery within 6 months. The presence of CDKN2A/B homozygous deletion, spinal or leptomeningeal disease, as well as prior chemotherapy, cranial irradiation or IDH inhibitor therapy, is exclusionary. 408 patients will be randomized 1:1 to receive vorasidenib 40 mg or placebo daily with 12 cycles of temozolomide following radiotherapy and then continued as monotherapy until disease progression or unacceptable toxicity. Stratification factors include age (< 40 years old vs ≥ 40 years old) and residual disease (< 2 cm vs ≥ 2 cm). Tumor assessments with MRI will be every three months for the first two years, every four months for the next two years and then every six months thereafter as per blinded independent central review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Key secondary endpoints include PFS by local review, time to next treatment, safety and tolerability, quality of life measures. Exploratory measures will include seizure frequency. The trial will have 85% power to detect a hazard ratio of 0.625 with one-sided type I error rate of 0.025. Enrollment for the trial commenced February 2026. Support: U10CA180821, U10CA180882, U24CA196171. https://acknowledgments.alliancefound.org.

e19023 Background: Undetectable measurable residual disease (uMRD) is associated with prolonged progression free survival in patients with chronic lymphocytic leukemia (CLL) (Rios-Olais et al., 2024). Peripheral blood (PB) MRD testing is less invasive and allows more frequent MRD monitoring than bone marrow (BM) MRD testing. As MRD testing and MRD-guided time-limited therapies become more common, there is a need to determine the concordance between rates of uMRD in the PB and BM. Methods: We performed a systematic review and meta-analysis of studies in CLL to determine the concordance between rates of uMRD in the PB and BM. Prospective clinical trials evaluating first-line, time-limited treatment of CLL with targeted agents or anti-CD20 monoclonal antibodies (mAbs) were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception until December 15 th , 2025. Studies were included if they reported rates of BM and PB uMRD at the same timepoint using the same method of MRD testing. Study arms evaluating chemotherapy, single-agent targeted therapy or single-agent anti-CD20 mAbs were excluded. Study sample size, number of patients receiving MRD testing, rates of uMRD in PB and BM, time and method of MRD testing, depth of MRD testing, and treatment arm were extracted. The agreement of uMRD rates between PB and BM was assessed using intraclass correlation coefficients (ICC). Results: 3128 studies were identified on initial search. After study selection criteria were applied, 24 timepoints across 12 prospective clinical trials were analyzed. Across all timepoints, 3121 PB and 2782 BM MRD measurements were included. All timepoints defined uMRD at a depth of under 0.01% CLL cells (10^-4). 20/24 timepoints utilized flow cytometry for MRD testing, 3 utilized allele-specific oligonucleotide PCR (ASO-PCR), and one utilized next-generation sequencing (NGS). 8 timepoints evaluated patients treated with a BTK inhibitor + venetoclax, 10 evaluated patients treated with venetoclax + an anti-CD20 mAb, and 6 evaluated patients treated with triplet therapy. The ICC between rates of uMRD in PB and BM was 0.925 (95% CI: 0.89, 0.95), indicating an excellent degree of agreement between the two methods of testing.(Koo & Li, 2016) The mean uMRD rates in PB and BM were 70.1% and 64.3%, respectively. The mean rate of uMRD in the PB was 5.87% (95% CI: -7.05, 18.80%) higher than in the BM; indicating a consistent slight bias of higher PB uMRD rates compared to BM across timepoints. Conclusions: Overall, we demonstrate that in patients with CLL treated with modern, time-limited therapy, there is high concordance in uMRD rates between PB and BM. Rates of uMRD in the PB are typically slightly higher than in BM.

Abstract Introduction Hypoglossal nerve stimulators (HGNS) are used in patients with moderate-to-severe obstructive sleep apnea (OSA) who are unable to tolerate or do not respond to continuous positive airway pressure (CPAP) therapy. However, a subgroup of patients fail to achieve resolution of OSA with HGNS alone. Previous studies have shown that lower BMI, lower nadir oxygenation, decreased sleep latency, and higher VOTE score on drug-induced sleep endoscopy (DISE) predict better treatment outcome. We hypothesize that baseline diagnostic polysomnography (PSG) may further predict which patients will achieve successful therapeutic outcome with HGNS therapy. Methods We conducted a retrospective analysis of all adult patients who underwent HGNS implantation at Mayo Clinic Arizona between 2019-2025 and had a pre-implantation diagnostic PSG available for review. Treatment success was defined by Sher Criteria: &gt;50% reduction in post-treatment apnea hypopnea index (AHI) to a final AHI of &lt; 20/hr. Responders met Sher criteria and non-responders did not meet Sher criteria. Demographics, sleep questionnaire results, PSG variables, and VOTE score on DISE were collected and analyzed using Spearman’s rank correlation of reduction in AHI. Results Twenty-three patients (11M/12F, median age: 69[IQR:64,75] years) met inclusion criteria. Median baseline AHI was 24[IQR:19,37]/hr. Median post-implant AHI was 8 [IQR:3, 14]/hr. Responders (n=15, 65%) and non-responders (n=8, 35%) demonstrated median post-implant AHI of 4.5[IQR:2.3,7.3]/hr and 15.7[IQR:12.3,28.5]/hr, respectively. Treatment response was associated with less time with SpO2 &lt; 88% (T88%) (21min [IQR:3,64] vs. 73[IQR:36,105mins]; p=0.023) and higher central apnea index (CAI) (1[IQR:0.1,3] vs. 0[IQR:0,1], p=0.03) on pre-implantation PSG. Conclusion In this small cohort of OSA patients, less nocturnal hypoxemia as defined by T88% and higher baseline central apnea index were predictors of better treatment response to HGNS therapy as measured by Sher criteria. We hypothesize that greater nocturnal hypoxemia likely reflects more severe airway obstruction during sleep. Our analysis also showed that responders had higher baseline CAI than non-responders, however we believe this association is not clinically significant and likely driven by one outlier (CAI 13/hr). Further analysis in a larger HGNS cohort is needed to confirm these findings. Data enrichment efforts and more sophisticated analyses are underway. Support (if any)