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  1. Kho SS, Tie ST
    Med J Malaysia, 2019 08;74(4):349-351.
    PMID: 31424050
    Solitary pulmonary nodule (SPN) always raises suspicion for early lung cancer, in which accurate and less invasive biopsy is needed. We report a case of transbronchial cryobiopsy of right upper lobe SPN under radial endobronchial ultrasound (R-EBUS) guidance after an inconclusive computed tomography guided transthoracic needle aspiration. A diagnosis of Stage 1B adenocarcinoma of the lung was made. Patient subsequently underwent curative right upper lobectomy after ruling out mediastinal lymph node involvement. To the best of our knowledge, this is the first report of R-EBUS guided transbronchial cryobiopsy case reported from Malaysia.
  2. Nyanti LE, Kho SS, Tie ST
    Med J Malaysia, 2019 02;74(1):79-81.
    PMID: 30846667
    Primary lung malignancy presenting as empyema is rare, with a reported incidence of 0.3%. We report a case of a 60- year-old man presenting with unilateral pleural effusion; diagnostic thoracocentesis confirmed Salmonella empyema. Post-drainage, chest radiograph showed persisting right hemithorax opacity; subsequent computed tomography revealed a right lung mass with right upper lobe bronchus obliteration. Percutaneous biopsy confirmed advanced stage lung adenocarcinoma. We discuss the mechanism of post-obstructive pneumonia in lung cancerassociated empyema and the utility of bedside ultrasound in diagnosis of lung masses. Clinicians are alerted to the possibility of lung malignancy in elderly patients presenting with empyema.
  3. Soo CI, Huan NC, Kho SS
    Med J Malaysia, 2024 Jul;79(4):490-493.
    PMID: 39086350
    Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used to diagnose and stage lung cancer. In clinical practice, cytology specimens from EBUS-TBNA may be low in cellularity, especially with necrotic lesions. Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TBMC) has recently become the preferred method for obtaining histology biopsy. This retrospective cohort study analysed the first 30 patients who have undergone EBUS-TBMC in a tertiary centre in Malaysia. EBUS-TBMC demonstrated a high diagnostic yield and good safety profile. All the samples obtained were adequate for the detection of driver alteration by next-generation sequencing.
  4. Kho SL, Chua KH, George E, Tan JA
    Genet. Mol. Res., 2013;12(3):2409-15.
    PMID: 23479149 DOI: 10.4238/2013.February.28.4
    Beta-thalassemia is a life-threatening inherited blood disorder. Rapid characterization of β-globin gene mutations is necessary because of the high frequency of Malaysian β-thalassemia carriers. A combination real-time polymerase chain reaction genotyping assay using TaqMan probes was developed to confirm β-globin gene mutations. In this study, primers and probes were designed to specifically identify 8 common β-thalassemia mutations in the Malaysian Malay and Chinese ethnic groups using the Primer Express software. "Blind tests" using DNA samples from healthy individuals and β-thalassemia patients with different genotypes were performed to determine the specificity and sensitivity of this newly designed assay. Our results showed 100% sensitivity and specificity for this novel assay. In conclusion, the TaqMan genotyping assay is a straightforward assay that allows detection of β-globin gene mutations in less than 40 min. The simplicity and reproducibility of the TaqMan genotyping assay permit its use in laboratories as a rapid and cost-effective diagnostic tool for confirmation of common β-thalassemia mutations in Malaysia.
  5. Kho SS, Chan SK, Yong MC, Tie ST
    Med J Malaysia, 2020 05;75(3):254-259.
    PMID: 32467541
    INTRODUCTION: Pleural effusion is frequently encountered in respiratory medicine. However, despite thorough assessment including closed pleural biopsy, the cause of around 20% of pleural effusions remains undetermined. Medical thoracoscopy (MT) is the investigation of choice in these circumstances especially if malignancy is suspected. The aim of this study is to evaluate the diagnostic yield of MT in exudative pleural effusions in a single center from East Malaysia.

    METHODS: Retrospective chart review of all adult patients who underwent MT for undiagnosed exudative pleural effusion in a 24-month duration.

    RESULTS: Our cohort comprised of 209 patients with a median age of 61 years old (IQR 48.5-69.5). There were 92 (44%) patients with malignant pleural effusion (MPE) and 117 (56%) benign effusions; which included 85 tuberculous pleural effusion (TBE) and 32 cases of non-tuberculous exudative pleural effusion. Conclusive pathological diagnosis was made in 79.4% of the cases. For diagnosis of MPE, MT had a sensitivity of 89.1% (95% CI 80.4-94.3), specificity of 100% (95% CI 96.0-100.0), and positive predictive value (PPV) of 100% (95% CI 94.4-100) and negative predictive value (NPV) of 92.1% (95% CI 85.6-95.9). For TBE, MT had a sensitivity of 90.5% (95% CI 81.8-95.6), specificity of 100% (95% CI 96.3- 100.0) PPV of 100% (95% CI 94.1-100) and NPV of 93.9% (95% CI 88.0-97.2). Overall complication rate was 3.3%.

    CONCLUSIONS: MT showed excellent sensitivity and specificity in the diagnosis of exudative pleural effusion in this region. It reduces empirical therapy by providing histological evidence of disease when initial non-invasive investigations were inconclusive.

  6. Kho SS, Chan SK, Yong MC, Tie ST
    Med J Malaysia, 2018 02;73(1):49-50.
    PMID: 29531204 MyJurnal
    Tuberculous pleural effusion (TBE) is a common encounter in our region. Up to 50% of patients with TBE will develop residual pleural thickening (RPT) which can lead to functional impairment. However, the need of drainage remains controversial. We report a case of end-stage renal failure patient who presented with right multiloculated tuberculous pleural effusion which was drained via a medical thoracoscope. Patient reports immediate relief of breathlessness post procedure and one month follow up shown significant improvement of RPT. We also discussed the current perspective on the rationale of TBE drainage and the role of medical thoracoscope in TBE management.
  7. Kho SS, Yong MC, Chan SK, Tie ST, Voon PJ
    Med J Malaysia, 2018 12;73(6):403-404.
    PMID: 30647213
    Malignant central airway obstruction (CAO) with ball valve effect (BVE) in the lung is rare. We discuss a case of metastatic colon cancer who presented with asthma like symptoms which thoracic computed tomography and bronchoscopy revealed an intraluminal tumour obstructing the left main bronchus in a ball valve manner. Airway patency was restored urgently with immediate alleviation of symptoms. This illustrates the importance of recognizing subtle features of central airway obstruction to allow expedition of appropriate investigations and therapy.
  8. Anstey NM, Grigg MJ, Rajahram GS, Cooper DJ, William T, Kho S, et al.
    Adv Parasitol, 2021;113:1-43.
    PMID: 34620381 DOI: 10.1016/bs.apar.2021.08.001
    Plasmodium knowlesi is endemic across Southeast Asia, and is the commonest cause of zoonotic malaria. The spectrum of clinical disease from P. knowlesi infection ranges from asymptomatic infection, through to severe malaria and death. Over 90% of clinical disease occurs in adults, mostly living in forest edge areas undergoing intensive land use change. With a 24-h asexual life cycle in humans, high parasite counts are possible, but most clinical cases of knowlesi malaria are uncomplicated with low parasitaemia. In co-endemic areas, median parasitaemia in knowlesi malaria is lower than that seen in vivax and falciparum malaria, suggesting a lower fever threshold. Severe malaria occurs in 6-9% of symptomatic adults. Manifestations of severe malaria from P. knowlesi are similar to those seen with falciparum malaria, with the notable absence of coma. Age, parasitaemia, cardiovascular comorbidities and delayed diagnosis are risk factors for severe disease and death, which are only seen in adults. Thrombocytopenia is near-universal in adults, likely related to platelet-red cell binding and clearance. Mechanisms underlying the microvascular sludging seen in fatal disease in non-natural primate hosts and the microvascular accumulation of parasites in fatal human disease are not clear. Marked reductions in deformability of both infected and uninfected red blood cells are associated with disease severity in both humans and other non-natural primate hosts, likely contributing to impaired microvascular perfusion and organ dysfunction. Endothelial activation, endothelial dysfunction, glycocalyx degradation and haemolysis are also associated with, and likely contribute to, severe disease and organ dysfunction, particularly acute kidney injury.
  9. Ngu NH, Chai CS, Chan SK, Kho SS, Yong MC, Tie ST
    Med J Malaysia, 2022 Nov;77(6):650-654.
    PMID: 36448380
    INTRODUCTION: Corticosteroids, particularly methylprednisolone, are part of the treatment for severe COVID-19 with acute respiratory distress syndrome (ARDS). In this study, we aimed to compare the mortalities of patients treated with higher versus lower doses of methylprednisolone. Secondary outcomes included oxygenation, need for mechanical ventilation, length of stay in intensive care unit (ICU), secondary infection, improvement of PaO2/FiO2 (PF) ratio, and inflammatory response as expressed by C-reactive protein (CRP).

    MATERIALS AND METHODS: A retrospective cohort study conducted at Sarawak General Hospital from 1st June to 30th September 2021. Patients who received intravenous methylprednisolone for severe COVID-19 in the ICU were identified and divided into two groups: higher dose (cumulative dose more than 10 mg per kg) and lower dose (cumulative dose less than 10 mg per kg).

    RESULTS: Out of a total of 165 patients, 40 (24.2%) patients received higher dose methylprednisolone. There was no significant difference in socio-demographic characteristics (age, gender, body mass index), COVID-19 vaccination status, laboratory parameters (lymphocyte count, CRP, lactate dehydrogenase, D-dimer), or usage of immunomodulator therapy between the groups. Overall mortality was 23.6%. Mortality in the higher dose group was twice as high compared to lower dose group (37.5% versus 19.2%) (OR 3.79, 95% CI 1.24-11.59, p<0.05). In addition, the higher dose cohort developed more secondary infections (87.5%) and had longer stays in ICU (median 11 days, IQR 8- 15). No significant difference was found between both cohorts in terms of CRP reduction, improvement of PF ratio, or the need for mechanical ventilation post methylprednisolone.

    CONCLUSION: In this study, the use of higher dose methylprednisolone in COVID-19 with ARDS was not associated with better clinical outcomes. A lower dose of methylprednisolone might be sufficient in treating severe COVID-19 with ARDS.

  10. Kho SS, Lim KC, Muhammad NA, Nasaruddin MZ, Ismail I, Daut UM, et al.
    Med J Malaysia, 2023 Mar;78(2):131-138.
    PMID: 36988520
    INTRODUCTION: COVID-19 patients frequently demonstrate radiological organising pneumonia (OP) pattern. The longterm outcome and treatment options for this group of patients remain uncertain. We aim to describe the clinical and radiological outcomes of patients with COVID-19-related OP and identify possible clinical factors associated with inferior radiological outcome.

    MATERIALS AND METHODS: Post-COVID-19 clinic attendees, consisting of post-COVID-19 patients discharged from major hospitals in the state of Selangor during the third pandemic wave of COVID-19 in Malaysia, were enrolled in this retrospective study for 6 months. Physician-scored Modified Medical Research Council (mMRC), patient self-reported quality of life (EQ-VAS) score and follow-up CT scan were evaluated.

    RESULTS: Our cohort comprised 131 patients, with a median age of 52 (IQR 39-60) years and median BMI of 29.40 (IQR 25.59-34.72). Majority (72.5%) had co-morbidities, and 97.7% had severe disease requiring supplementary oxygen support during the acute COVID-19 episode. 56.5% required intensive care; among which one-third were invasively ventilated. Median equivalent dose of methylprednisolone prescribed was 2.60 (IQR 1.29-5.18) mg/kg during admission, while the median prednisolone dose upon discharge was 0.64 (IQR 0.51-0.78) mg/kg. It was tapered over a median of 8.0 (IQR 5.8-9.0) weeks. Upon follow-up at 11 (IQR 8-15) weeks, one-third of patients remained symptomatic, with cough, fatigue and dyspnoea being the most reported symptoms. mMRC and EQ-VAS scores improved significantly (p<0.001) during follow-up. Repeat CT scans were done in 59.5% of patients, with 94.8% of them demonstrating improvement. In fact, 51.7% had complete radiological resolution. Intensive care admission and mechanical ventilation are among the factors which were associated with poorer radiological outcomes, p<0.05.

    CONCLUSION: Approximately one-third of patients with SARSCoV- 2-related OP remained symptomatic at 3 months of follow-up. Majority demonstrated favourable radiological outcomes at 5-month reassessment, except those who required intensive care unit admission and mechanical ventilation.

  11. Kho SS, Aziz AA, Sia TLL, Ramarmuty HY, Sirol Aflah SS, Mohamed Gani Y, et al.
    Med J Malaysia, 2023 May;78(3):279-286.
    PMID: 37271836
    INTRODUCTION: Cluster-associated transmission has contributed to the majority of COVID-19 cases in Malaysia. Although widely used, the performance of the World Health Organization (WHO) case definition for suspected COVID19 in environments with high numbers of such cases has not been reported.

    MATERIALS AND METHODS: All suspected cases of COVID-19 that self-presented to hospitals or were cluster screened from 1st April to 31st May 2020 were included. Positive SARS-CoV-2 rRT-PCR was used as the diagnostic reference for COVID-19.

    RESULTS: 540 individuals with suspected COVID-19 were recruited. Two-third of patients were identified through contact screening, while the rest presented sporadically. Overall COVID-19 positivity rate was 59.4% (321/540) which was higher in the cluster screened group (85.6% vs. 11.6%, p<0.001). Overall, cluster-screened COVID-19 cases were significantly younger, had fewer comorbidities and were less likely to be symptomatic than those present sporadically. Mortality was significantly lower in the cluster-screened COVID-19 cases (0.3% vs. 4.5%, p<0.05). A third of all chest radiographs in confirmed COVID-19 cases were abnormal, with consolidation, ground-glass opacities or both predominating in the peripheral lower zones. The WHO suspected case definition for COVID-19 accurately classified 35.4% of all COVID-19 patients, a rate not improved by the addition of baseline radiographic data. Misclassification rate was higher among the cluster-associated cases (80.6%) compared to sporadic cases (35.3%).

    CONCLUSION: COVID-19 cases in Malaysia identified by active tracing of community cluster outbreaks had lower mortality rate. The WHO suspected COVID-19 performed poorly in this setting even when chest radiographic information was available, a finding that has implications for future spikes of the disease in countries with similar transmission characteristics.

  12. Tan AF, Sakam SSB, Piera K, Rajahram GS, William T, Barber BE, et al.
    PLoS Negl Trop Dis, 2024 Aug;18(8):e0012424.
    PMID: 39150978 DOI: 10.1371/journal.pntd.0012424
    The risk of severe malaria from the zoonotic parasite Plasmodium knowlesi approximates that from P. falciparum. In severe falciparum malaria, neutrophil activation contributes to inflammatory pathogenesis, including acute lung injury (ALI). The role of neutrophil activation in the pathogenesis of severe knowlesi malaria has not been examined. We evaluated 213 patients with P. knowlesi mono-infection (138 non-severe, 75 severe) and 49 Plasmodium-negative controls from Malaysia. Markers of neutrophil activation (soluble neutrophil elastase [NE], citrullinated histone [CitH3] and circulating neutrophil extracellular traps [NETs]) were quantified in peripheral blood by microscopy and immunoassays. Findings were correlated with malaria severity, ALI clinical criteria, biomarkers of parasite biomass, haemolysis, and endothelial activation. Neutrophil activation increased with disease severity, with median levels higher in severe than non-severe malaria and controls for NE (380[IQR:210-930]ng/mL, 236[139-448]ng/mL, 218[134-307]ng/mL, respectively) and CitH3 (8.72[IQR:3.0-23.1]ng/mL, 4.29[1.46-9.49]ng/mL, 1.53[0.6-2.59]ng/mL, respectively)[all p<0.01]. NETs were higher in severe malaria compared to controls (126/μL[IQR:49-323] vs 51[20-75]/μL, p<0.001). In non-severe malaria, neutrophil activation fell significantly upon discharge from hospital (p<0.03). In severe disease, NETs, NE, and CitH3 were correlated with parasitaemia, cell-free haemoglobin and angiopoietin-2 (all Pearson's r>0.24, p<0.05). Plasma NE and angiopoietin-2 were higher in knowlesi patients with ALI than those without (p<0.008); neutrophilia was associated with an increased risk of ALI (aOR 3.27, p<0.01). In conclusion, neutrophil activation is increased in ALI and in proportion to disease severity in knowlesi malaria, is associated with endothelial activation, and may contribute to disease pathogenesis. Trials of adjunctive therapies to regulate neutrophil activation are warranted in severe knowlesi malaria.
  13. Tan AF, Thota P, Sakam SSB, Lew YL, Rajahram GS, William T, et al.
    Sci Rep, 2023 Mar 23;13(1):4760.
    PMID: 36959462 DOI: 10.1038/s41598-023-31839-7
    Plasmodium knowlesi is the major cause of zoonotic malaria in Southeast Asia. Rapid and accurate diagnosis enables effective clinical management. A novel malaria diagnostic tool, Gazelle (Hemex Health, USA) detects haemozoin, a by-product of haem metabolism found in all Plasmodium infections. A pilot phase refined the Gazelle haemozoin identification algorithm, with the algorithm then tested against reference PCR in a larger cohort of patients with P. knowlesi mono-infections and febrile malaria-negative controls. Limit-of-detection analysis was conducted on a subset of P. knowlesi samples serially diluted with non-infected whole blood. The pilot phase of 40 P. knowlesi samples demonstrated 92.5% test sensitivity. P. knowlesi-infected patients (n = 203) and febrile controls (n = 44) were subsequently enrolled. Sensitivity and specificity of the Gazelle against reference PCR were 94.6% (95% CI 90.5-97.3%) and 100% (95% CI 92.0-100%) respectively. Positive and negative predictive values were 100% and 98.8%, respectively. In those tested before antimalarial treatment (n = 143), test sensitivity was 96.5% (95% CI 92.0-98.9%). Sensitivity for samples with ≤ 200 parasites/µL (n = 26) was 84.6% (95% CI 65.1-95.6%), with the lowest parasitaemia detected at 18/µL. Limit-of-detection (n = 20) was 33 parasites/µL (95% CI 16-65%). The Gazelle device has the potential for rapid, sensitive detection of P. knowlesi infections in endemic areas.
  14. Goh SY, Ang E, Bajpai S, Deerochanawong C, Hong EG, Hussein Z, et al.
    J Diabetes Complications, 2016 08;30(6):973-80.
    PMID: 27288201 DOI: 10.1016/j.jdiacomp.2016.05.019
  15. Tan AF, Sakam SSB, Rajahram GS, William T, Abd Rachman Isnadi MF, Daim S, et al.
    Front Cell Infect Microbiol, 2022;12:1023219.
    PMID: 36325471 DOI: 10.3389/fcimb.2022.1023219
    BACKGROUND: Plasmodium knowlesi causes zoonotic malaria across Southeast Asia. First-line diagnostic microscopy cannot reliably differentiate P. knowlesi from other human malaria species. Rapid diagnostic tests (RDTs) designed for P. falciparum and P. vivax are used routinely in P. knowlesi co-endemic areas despite potential cross-reactivity for species-specific antibody targets.

    METHODS: Ten RDTs were evaluated: nine to detect clinical P. knowlesi infections from Malaysia, and nine assessing limit of detection (LoD) for P. knowlesi (PkA1-H.1) and P. falciparum (Pf3D7) cultures. Targets included Plasmodium-genus parasite lactate dehydrogenase (pan-pLDH) and P. vivax (Pv)-pLDH.

    RESULTS: Samples were collected prior to antimalarial treatment from 127 patients with microscopy-positive PCR-confirmed P. knowlesi mono-infections. Median parasitaemia was 788/µL (IQR 247-5,565/µL). Pan-pLDH sensitivities ranged from 50.6% (95% CI 39.6-61.5) (SD BIOLINE) to 87.0% (95% CI 75.1-94.6) (First Response® and CareStart™ PAN) compared to reference PCR. Pv-pLDH RDTs detected P. knowlesi with up to 92.0% (95% CI 84.3-96.7%) sensitivity (Biocredit™). For parasite counts ≥200/µL, pan-pLDH (Standard Q) and Pv-pLDH RDTs exceeded 95% sensitivity. Specificity of RDTs against 26 PCR-confirmed negative controls was 100%. Sensitivity of six highest performing RDTs were not significantly different when comparing samples taken before and after (median 3 hours) antimalarial treatment. Parasite ring stages were present in 30% of pre-treatment samples, with ring stage proportions (mean 1.9%) demonstrating inverse correlation with test positivity of Biocredit™ and two CareStart™ RDTs.For cultured P. knowlesi, CareStart™ PAN demonstrated the lowest LoD at 25 parasites/µL; LoDs of other pan-pLDH ranged from 98 to >2000 parasites/µL. Pv-pLDH LoD for P. knowlesi was 49 parasites/µL. No false-positive results were observed in either P. falciparum-pLDH or histidine-rich-protein-2 channels.

    CONCLUSION: Selected RDTs demonstrate sufficient performance for detection of major human malaria species including P. knowlesi in co-endemic areas where microscopy is not available, particularly for higher parasite counts, although cannot reliably differentiate among non-falciparum malaria.

  16. Kho S, Barber BE, Johar E, Andries B, Poespoprodjo JR, Kenangalem E, et al.
    Blood, 2018 Sep 20;132(12):1332-1344.
    PMID: 30026183 DOI: 10.1182/blood-2018-05-849307
    Platelets are understood to assist host innate immune responses against infection, although direct evidence of this function in any human disease, including malaria, is unknown. Here we characterized platelet-erythrocyte interactions by microscopy and flow cytometry in patients with malaria naturally infected with Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium knowlesi Blood samples from 376 participants were collected from malaria-endemic areas of Papua, Indonesia, and Sabah, Malaysia. Platelets were observed binding directly with and killing intraerythrocytic parasites of each of the Plasmodium species studied, particularly mature stages, and was greatest in P vivax patients. Platelets preferentially bound to the infected more than to the uninfected erythrocytes in the bloodstream. Analysis of intraerythrocytic parasites indicated the frequent occurrence of platelet-associated parasite killing, characterized by the intraerythrocytic accumulation of platelet factor-4 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling of parasite nuclei (PF4+TUNEL+ parasites). These PF4+TUNEL+ parasites were not associated with measures of systemic platelet activation. Importantly, patient platelet counts, infected erythrocyte-platelet complexes, and platelet-associated parasite killing correlated inversely with patient parasite loads. These relationships, taken together with the frequency of platelet-associated parasite killing observed among the different patients and Plasmodium species, suggest that platelets may control the growth of between 5% and 60% of circulating parasites. Platelet-erythrocyte complexes made up a major proportion of the total platelet pool in patients with malaria and may therefore contribute considerably to malarial thrombocytopenia. Parasite killing was demonstrated to be platelet factor-4-mediated in P knowlesi culture. Collectively, our results indicate that platelets directly contribute to innate control of Plasmodium infection in human malaria.
  17. Chan ATC, Lee VHF, Hong RL, Ahn MJ, Chong WQ, Kim SB, et al.
    Ann Oncol, 2023 Mar;34(3):251-261.
    PMID: 36535566 DOI: 10.1016/j.annonc.2022.12.007
    BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented.

    PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population.

    RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage).

    CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

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