Hospital Tengku Ampuan Afzan

INTRODUCTION:TIGIT and PD-1 trigger distinct but interconnected immunosuppressive pathways. We investigated first-line domvanalimab (Fc-silent anti-TIGIT) plus zimberelimab (anti-PD-1) in PD-L1-high (≥50%), stage IIIB-IV NSCLC. MATERIALS AND METHODS:This phase 2, multicenter, randomized, open-label study (ARC-10, Part 1) randomized (2:2:1) patients to intravenous domvanalimab 15 mg/kg plus zimberelimab 360 mg (DZ), zimberelimab 360 mg (Z), or platinum-doublet chemotherapy every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), confirmed objective response rate (ORR), and safety. RESULTS:Of 98 randomized patients, 95 received treatment (DZ, n = 38; Z, n = 40; chemotherapy, n = 17). As of May 17, 2024, median follow-up was 24.5 months; 22patients remained on first-line treatment (DZ, n = 11; Z, n = 10; chemotherapy, n = 1). Median (95% CI) PFS was 11.5 (4.0-26.2) months for DZ, 6.2 (2.5-12.3) months for Z, and 9.6 (2.6-16.4) months for chemotherapy. Median (95% CI) OS was not reached (13.7-not evaluable [NE]) for DZ, 24.4(7.8-NE) months for Z, and 11.9(2.7-NE) months for chemotherapy. DZ vs Z hazard ratio (95% CI) was 0.69 (0.40-1.18) for PFS and 0.64 (0.32-1.25) for OS. ORR (95% CI) was 44.7% (28.6-61.7) for DZ, 35.0% (20.6-51.7) for Z, and 35.3% (14.2-61.7) for chemotherapy. Grade ≥ 3 treatment-related adverse events (AEs) were lower for DZ (21.1%) and Z (15.0%) vs chemotherapy (47.1%). Immune-mediated AEs were similar between DZ (23.7%) and Z (20.0%). Infusion-related reactions were low (0%-7.9% across arms). CONCLUSIONS:Adding Fc-silent anti-TIGIT (domvanalimab) to anti-PD-1 (zimberelimab) led to encouraging efficacy and showed no new safety concerns in patients with previously untreated stage IIIB-IV NSCLC.

This case report discusses a 16-year-old male patient with a history of recurrent allergic rhinitis and sinusitis, who initially presented with left eyelid swelling, proptosis, and progressive facial edema extending from the left medial canthus to the nasal bridge. He was treated for nearly a year under the working diagnosis of chronic left dacryocystitis with multiple courses of topical, oral, and intravenous antibiotics. However, the patient developed worsening proptosis, progressive left-sided vision loss, and left submandibular lymphadenopathy, which ultimately guided the diagnostic focus toward ocular adnexal lymphoma (OAL) involving the left orbit. Despite multiple imaging studies and histopathological assessments, it took nearly a year to identify the exact pathology. This case report details the diagnostic journey, treatment strategies, and interventions employed to preserve the patient's vision, ultimately enabling him to resume normal activities. We emphasize that in cases of chronic, unresponsive dacryocystitis, ocular adnexal lymphoma should be considered in the differential diagnosis. Early surgical intervention plays a critical role in optimizing visual outcomes and should be pursued to avoid further morbidity associated with delayed diagnosis.