Malaysia is an endemic hot spot for melioidosis; however, a comprehensive picture of the burden of disease, clinical presentations, and challenges faced in diagnosis and treatment of melioidosis is not available. This review provides a nonexhaustive overview of epidemiological data, clinical studies, risk factors, and mortality rates from available literature and case reports. Clinical patterns of melioidosis are generally consistent with those from South and Southeast Asia in terms of common primary presentations with diabetes as a major risk factor. Early diagnosis and appropriate management of Malaysian patients is a key limiting factor, which needs to be addressed to reduce serious complications and high mortality and recurrence rates. Promoting awareness among the local healthcare personnel is crucial to improving diagnostics and early treatment, as well as educating the Malaysian public on disease symptoms and risk factors. A further matter of urgency is the need to make this a notifiable disease and the establishment of a national melioidosis registry. We also highlight local studies on the causative agent, Burkholderia pseudomallei, with regards to bacteriology and identification of virulence factors as well as findings from host–pathogen interaction studies. Collectively, these studies have uncovered new correlations and insights for further understanding of the disease.

Co-infection of melioidosis and leptospirosis is uncommon. We report here four such cases, confirmed by blood culture for melioidosis and blood polymerase-chain reaction for leptospirosis, which occurred among rescuers involved in a search and rescue operation for a young man who was suspected to have drowned in Lubuk Yu, a recreational forest in Pahang, Malaysia. Despite treatment, three of the patients died from the co-infection.

Background: This study aimed to evaluate the efficacy, side-effects and resistance mechanisms of first-line afatinib in a real-world setting. Methods: This is a multicenter observational study of first-line afatinib in Malaysian patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC). Patients’ demographic, clinical and treatment data, as well as resistance mechanisms to afatinib were retrospectively captured. The statistical methods included Chi-squared test and independent t-test for variables, Kaplan-Meier curve and log-rank test for survival, and Cox regression model for multivariate analysis. Results: Eighty-five patients on first-line afatinib from 1st October 2014 to 30th April 2018 were eligible for the study. EGFR mutations detected in tumors included exon 19 deletion in 80.0%, exon 21 L858R point mutation in 12.9%, and rare or complex EGFR mutations in 7.1% of patients. Among these patients, 18.8% had Eastern Cooperative Oncology Group performance status of 2–4, 29.4% had symptomatic brain metastases and 17.6% had abnormal organ function. Afatinib 40 mg or 30 mg once daily were the most common starting and maintenance doses. Only one-tenth of patients experienced severe side-effects with none having grade 4 toxicities. The objective response rate was 76.5% while the disease control rate was 95.3%. At the time of analysis, 56 (65.9%) patients had progression of disease (PD) with a median progression-free survival (mPFS) of 14.2 months (95% CI, 11.85–16.55 months). Only 12.5% of the progressed patients developed new symptomatic brain metastases. The overall survival (OS) data was not mature. Thirty-three (38.8%) patients had died with a median OS of 28.9 months (95% CI, 19.82–37.99 months). The median follow-up period for the survivors was 20.0 months (95% CI, 17.49–22.51 months). Of patients with PD while on afatinib, 55.3% were investigated for resistance mechanisms with exon 20 T790 M mutation detected in 42.0% of them. Conclusions: Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with a good response rate and long survival, even in patients with unfavorable clinical characteristics. The side-effects of afatinib were manageable and T790 M mutation was the most common resistance mechanism causing treatment failure.

In the recent years, increased understanding of the molecular profiles of non-small cell lung cancer (NSCLC) has allowed for targeted treatment of actionable genetic mutations. The management of NSCLC now requires multiple molecular tests to guide the treatment strategy. In the light of this, there is a need to establish a molecular testing consensus statement for advanced NSCLC patients in Malaysia. This Malaysian consensus statement was developed by a panel of experts, chaired by a pathologist and composed of three other pathologists, four respiratory physicians and three oncologists. It reflects currently available scientific data and adaptations of recommendations from international guidelines to the local landscape. Expert recommendations on different aspects of molecular testing agreed upon by the panel are provided as structured discussions. These recommendations address the appropriate patients and samples to be tested, as well as when and how these tests should be performed. The algorithms for molecular testing in metastatic NSCLC, in the first line setting and upon disease progression beyond first line therapy, were developed.

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. 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. 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). 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.