Shahzad, Moazzam

The therapeutic landscape of adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is undergoing a paradigm shift, driven by the development of immunotherapy-based “chemo-free” and “chemo-light’ regimens. These strategies aim to achieve high efficacy with reduced toxicity, particularly in older adults who may not tolerate intensive chemotherapy. In Philadelphia chromosome-positive (Ph+) BCP-ALL, the incorporation of ABL tyrosine kinase inhibitors (TKIs) with blinatumomab (CD3/CD19 bispecific T-cell engager) has shown remarkable efficacy, with some studies reporting molecular response rates in the range of 90–100% and long-term survival exceeding 80% without the need for intensive chemotherapy or allogeneic hematopoietic cell transplantation (allo-HCT). In Philadelphia-negative (Ph−) BCP- ALL, an immunotherapy-based combination of blinatumomab and inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) has demonstrated high rates of complete remission and measurable residual disease (MRD) negativity, with manageable toxicity. While chimeric antigen receptor (CAR) T-cell therapy remains a transformative option for relapsed/refractory B-ALL, its integration into frontline treatment is still under investigation. Ongoing trials are evaluating the optimal sequencing and combinations of these agents and their potential to obviate the need for chemotherapy and/or allo-HCT in selected patients. As evidence continues to accumulate, chemo-free and chemo-light regimens, incorporating minimal chemotherapy with targeted agents to balance efficacy and reduced toxicity, are poised to redefine the standard of care for adults BCP-ALL, offering the possibility of durable remissions with reduced treatment-related morbidity.

e20593 Background: Tislelizumab, an anti-PD-1 antibody, is emerging as a promising immunotherapy agent and has demonstrated clinical benefit and acceptable tolerability in recent lung cancer trials. This study aims to assess the safety and efficacy of Tislelizumab, as monotherapy or combined with chemotherapy (Group 1), as a superior treatment alternative for lung cancer compared to standard chemotherapy (Group 2) in improving patient outcomes. Methods: Following PRISMA guidelines, a systematic search was conducted through MEDLINE, Embase, Scopus, Science Direct, Cochrane (CENTRAL), and ClinicalTrials.gov from inception to December 2024 to identify Randomized Control Trials (RCTs). Hazards ratio (HRs) and risk ratios (RRs) were generated, by employing a Random-effects model with a 95% confidence interval (CI). Statistical analysis was performed using RevMan 5.4, with statistical significance set at p<0.05. Our outcomes of interest were Progression Free Survival (PFS), Overall Survival (OS), Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of response (DOR), and treatment-related adverse Events. Results: A total of 6 RCTs involving 2107 patients were included for analysis. Pooled analysis demonstrated that Group 1 significantly improved PFS, OS, and DOR with HRs of 1.85 (95% CI: 1.71-1.99; p <0.00001, I² = 0%), 2.01 (95% CI: 1.75-2.29; p <0.00001, I² = 0%) and 2.14 (95% CI: 1.52-3.03; p <0.0001, I² = 39%), respectively. Group 1 has better DCR and ORR compared to Group 2 with RRs of 1.52 (95% CI: 1.12-2.07; p= 0.007, I² = 97%) and 1.50 (95% CI: 1.20-1.86; p= 0.0003, I² = 83%), respectively. The high heterogeneity observed in the pooled analysis of DCR (I² = 97%) and ORR (I² = 83%) likely reflects variability in study populations, treatment protocols, and response assessment criteria across the included RCTs. Subgroup or sensitivity analyses could help identify contributing factors. Despite the heterogeneity, the pooled effect sizes indicate a statistically significant improvement in DCR and ORR with Tislelizumab, with caution warranted when generalizing these findings. Group 1 significantly reduced all-cause mortality compared to Group 2 (RR = 0.89; 95% CI: 0.83–0.95; p = 0.0003), with no heterogeneity (I² = 0%). No significant differences were found in adverse events, except for ALT elevations. (RR = 1.36; 95% CI: 1.14–1.61; p = 0.0006, I² = 25%). Conclusions: Tislelizumab, with or without chemotherapy, demonstrates greater PFS and OS benefits compared to chemotherapy alone in patients with lung cancer. There was a significantly reduced all-cause mortality in the intervention group; however, the observed increase in the risk of ALT elevation underscores the need for vigilant liver function monitoring. When combined with chemotherapy, Tislelizumab presents a promising treatment option for lung cancer.

e13718 Background: Colorectal cancer (CRC) is the third-leading cancer worldwide and racial minorities bear a disproportionate burden of this disease. Methods: We searched the clinicaltrials.gov database for all the completed clinical trials conducted on adult patients until 2023 in the United States. In intervention trials, we manually abstracted data on the racial distribution of enrollees, phases, tumor histology, intervention type, and year of completion. We divided interventions into chemotherapy, radiotherapy, surgery, immunotherapy, behavioral, diagnostic tests, and others. To quantify the racial disparity, we calculated the enrolment ratio (ER) as the observed ratios of racial participation in the study compared to the prevalence in colorectal cancer per the 2009-2019 Surveillance, Epidemiology and End Results (SEER) database. We also conducted subgroup racial enrollment based on clinical trial and type of intervention. Results: We identified 394 studies, of which 252 studies (64%) had racial distribution published, including 138814 participants. Most studies were phase 2 trials (168), followed by phase 1/2 trials (49) and phase 3 studies (43). The racial breakdown included 88677 White participants (63.9%), 23230 were African Americans (16.7%), 9963 were Asians (7.1%), 4398 were of other races (3.2%), and 12546 were of unknown race (9.0%). The frequency of including racial data was 100% in Phase 1 studies, 56.5% in Phase 2, 58.1% in Phase 3, and only 16% in Phase 4. A total of 185 were immunotherapy trials, out of which 63 studied chemotherapies, radiotherapy and/ or surgery along with immunotherapy. Racial enrolment data was reported in 68.6 %, 58% and 59.3% in immunotherapy, chemotherapy, and radiotherapy interventions respectively. The ERs of whites, blacks, and Asians were 0.8, 1.3, and 0.9, respectively (Table). However, ER in subgroups with specific interventions, such as chemotherapy, immunotherapy, and radiotherapy, were 0.5, 0.4, and 0.6, respectively. Conclusions: African Americans are underrepresented in CRC intervention trials. Equal access and tailored strategies for cultural and linguistic differences are needed for fair participation. [Table: see text]