Piyarat Limpawittayakul’s research while affiliated with Chulabhorn Royal Academy and other places

PURPOSE Corticosteroids are known to diminish immune response ability, which is generally used in routine premedication for chemotherapy. The intersecting of timeframe between the corticosteroid's duration of action and peak COVID-19 vaccine efficacy could impair vaccine immunogenicity. Thus, inquiring about corticosteroids affecting the efficacy of vaccines to promote effective immunity in this population is needed. METHODS This was a prospective longitudinal observational cohort study that enrolled patients with solid cancer classified into dexamethasone- and nondexamethasone-receiving groups. All participants were immunized with two doses of ChAdOx1 nCoV-19 or CoronaVac vaccines. This study's purpose was to compare corticosteroid's effect on immunogenicity responses to the SARS-CoV-2 S protein in patients with cancer after two doses of COVID-19 vaccine in the dexamethasone and nondexamethasone group. Secondary outcomes included the postimmunization anti–spike (S) immunoglobin G (IgG) seroconversion rate, the association of corticosteroid dosage, time duration, and immunogenicity level. RESULTS Among the 161 enrolled patients with solid cancer, 71 and 90 were in the dexamethasone and nondexamethasone groups, respectively. The median anti–S IgG titer after COVID-19 vaccination in the dexamethasone group was lower than that in the nondexamethasone group with a statistically significant difference (47.22 v 141.09 U/mL, P = .035). The anti–S IgG seroconversion rate was also significantly lower in the dexamethasone group than in the nondexamethasone group (93.83% v 80.95%, P = .023). The lowest median anti–SARS-CoV-2 IgG titer level at 7.89 AU/mL was observed in patients with the highest dose of steroid group (≥37 mg of dexamethasone cumulative dose throughout the course of chemotherapy [per course]) and patients who were injected with COVID-19 vaccines on the same day of receiving dexamethasone, 25.41 AU/mL. CONCLUSION Patients with solid cancer vaccinated against COVID-19 disease while receiving dexamethasone had lower immunogenicity responses than those who got vaccines without dexamethasone. The direct association between the immunogenicity level and steroid dosage, as well as length of duration from vaccination to dexamethasone, was observed.

Background Paclitaxel is a chemotherapeutic drug widely used in breast cancer treatment. While common side effects are possible, paclitaxel-induced pneumonitis is rare, with an estimated incidence of 1%–5% and a high mortality rate. Case presentation A 57-year-old Thai woman diagnosed with stage II right breast cancer. She received adjuvant chemotherapy comprising doxorubicin and cyclophosphamide, followed by weekly paclitaxel. After the ninth paclitaxel cycle, she developed acute respiratory failure. Transbronchial biopsies revealed acute fibrinous and organizing pneumonitis. The patient was placed in prone position. Following the administration of dexamethasone, her symptoms improved. However, while reducing the dexamethasone dosage, she developed new-onset dyspnea as well as Takotsubo cardiomyopathy. Intravenous methylprednisolone 500 mg/day was administered for 3 days followed by transition to intravenous dexamethasone and slow tapering to prednisolone. Prednisolone was gradually tapered and eventually discontinued after 3 months. Conclusions Paclitaxel-induced pneumonitis is a rare complication. The diagnosis should be considered in any patient who develops respiratory symptoms while receiving paclitaxel. Acute fibrinous and organizing pneumonitis is a rare type of interstitial pneumonitis with high recurrence and mortality rates. High-dose steroids are needed to treat this type of pneumonitis.

Title: Efficacy of Monoclonal antibody Tixagevimab/Cilgavimab for prevention of SARS-CoV-2 infection among cancer patients : Double blined Randomized placebo Controlled trail (ProvMAB trial) Introduction Immunocompromised patients, particularly those with a Hematological malignancies or Oncologic malignancies, are at higher risk of SARS-Cov-2 infection, severe outcomes and mortality. Tixagevimab/Cilgavimab is a monoclonal antibody combination which binds to the SARS-CoV-2 spike protein. The PROVENT phase III clinical trial reported that Tixagevimab/Cilgavimab prophylaxis significantly reduced the risk of COVID-19 infection in immunocompromised participants who had not been vaccinated prior to enrollment. However, it should be noted that this trial was conducted before the emergence of the Omicron variant. While the approved Tixagevimab/Cilgavimab combination has demonstrated the ability to decrease the rate of symptomatic SARS-CoV-2 infection in patients at higher risk of inadequate response to vaccination. However, Tixagevimab/Cilgavimab was tested in a few studies that included patients with hematologic malignancies and oncologic malignancies, even if this population has shown an increased risk of unfavorable outcomes following infection (with high rates of hospitalization, intensive care unit admission, and mortality) and poor significant immunization following vaccines. Method We performed a randomized clinical trial double blind study to evaluate the rate of SARS-CoV-2 infection following pre-exposure prophylaxis with Tixagevimab/Cilgavimab 150/150 mg versus placebo in Hematologic malignancies and Oncologic malignancies patients who were on active treatment with systemic chemotherapy within 6 months. These patients received at least three doses of vaccination before enrollment, and neutralizing antibody and anti-spike antibody levels were measured at day 0, day 30, day 90 and day 180 after enrollment. The study was started from September 7, 2022, until July 19,2023, with a follow-up period of 180 days for all cases. Result A total of 138 participants were recruited, with 68 patients in the intervention arm and 70 patients in the placebo arm. The mean age in the intervention arm was 58 years old, while it was 59 years old in the placebo arm. The cumulative incidence of Covid-19 infection was 7.4% in intervention arm compared to 7.15% in the placebo arm (HR= 1.04; 95% CI :0.3 to 3.58, p-value=0.956). Covid-19-related-hopitalizations were 5.9% of the intervention arm and 1.4% of the placebo arm. No patients need to admit ICU in both arms. No deaths due to Covid-19 infection were reported during the study. Discussion In this study, we present our findings comparing Tixagevimab/Cilgavimab in immunocompromised patients who received over three doses of vaccination for the prevention of SARS-CoV-2 infection in patients with hematologic malignancies and Oncologic malignancies undergoing chemotherapy during the SARS-CoV-2 omicron surge. Our results suggest that booster vaccinations, beyond the standard three doses, were sufficient to protect against SARS-CoV-2 infection in this particular patient population, considering their ongoing standard of care during the pandemic variant in the future. Keywords: SARS-CoV-2, COVID-19, Tixagevimab/Cilgavimab, Hematological malignances, monoclonal antibodies

Background: Paclitaxel is a chemotherapeutic drug widely used in breast cancer treatment. While common side effects are possible, paclitaxel-induced pneumonitis is rare, with an estimated incidence of 1%–5% and a high mortality rate. Case presentation: A 57-year-old Thai woman was diagnosed with stage II right breast cancer. She received adjuvant chemotherapy comprising doxorubicin and cyclophosphamide, followed by weekly paclitaxel. After the ninth paclitaxel cycle, she developed progressive dyspnea and acute respiratory failure. Empirical antibiotic therapy with meropenem, levofloxacin, oseltamivir, and trimethoprim-sulfamethoxazole was initiated to address potential bacterial/viral pneumonias and Pneumocystis carinii pneumonia. Transbronchial biopsies revealed acute fibrinous and organizing pneumonitis. The patient was placed in the prone position, and a muscle relaxant was administered. Following the administration of dexamethasone, her symptoms improved. However, while reducing the dexamethasone dosage, she developed new-onset dyspnea as well as tachy-brady arrhythmia and hypotension. Echocardiography revealed Takotsubo cardiomyopathy (stress-induced cardiomyopathy). Intravenous methylprednisolone 500 mg/day was administered for 3 days followed by transition to intravenous dexamethasone and slow tapering to prednisolone. Prednisolone was gradually tapered and eventually discontinued after 3 months. Discussion and Conclusions: Paclitaxel-induced pneumonitis is a rare complication. The diagnosis should be considered in any patient who develops respiratory symptoms while receiving paclitaxel. Acute fibrinous and organizing pneumonitis is a rare type of interstitial pneumonitis with high recurrence and mortality rates. High-dose steroids are needed to treat this type of pneumonitis.

127 Background: Corticosteroids are known to diminish immune response ability, which is generally used in routine pre-medication for chemotherapy. The intersecting of timeframe between the corticosteroid’s duration of action and peak COVID-19 vaccine efficacy could impair vaccine immunogenicity. Thus, inquiring about corticosteroids affecting the efficacy of vaccines, a dose of corticosteroids, and optimal timing of vaccination to promote effective immunity in this population is needed. Methods: This was a prospective longitudinal observational cohort study that enrolled solid cancer patients classified into dexamethasone and non-dexamethasone receiving groups. All participants were immunized with two doses of ChAdOx1 nCoV-19 or CoronaVac vaccines. This study's purpose was to compare corticosteroid's effect on immunogenicity responses to the SARS-CoV-2 S protein in solid cancer patients following two doses of COVID-19 vaccine in the dexamethasone and non-dexamethasone group. Secondary outcomes included the post-immunization anti-S IgG seroconversion rate, the association of corticosteroid dosage, time duration and immunogenicity level. Results: Among the 161 enrolled solid cancer patients, 71 and 90 were in the dexamethasone and non- dexamethasone groups, respectively. The median anti-S IgG titer after COVID-19 vaccination in the dexamethasone group was lower than non- dexamethasone group with a statistically significant difference (47.22 vs 141.09 U/ml, p = 0.035). The anti-S IgG seroconversion rate was also significantly lower in the dexamethasone group than in the non- dexamethasone group (93.83% vs 80.95% p = 0.023). The lowest median anti-SARS-CoV-2 IgG titer level at 7.89 AU/ml showed in patients with the highest dose of steroid group (37 mg or more of dexamethasone) and patients who were injected with COVID-19 vaccines on the same day of receiving dexamethasone, 25.41 AU/ml. Conclusions: Solid cancer patients vaccinated against COVID-19 while receiving dexamethasone had lower immunogenicity responses than those who got vaccines without dexamethasone, regardless of active cancer treatment types.The direct association between immunogenicity level and steroid dosage, as well as length of duration from vaccination to dexamethasone was observed. Clinical trial information: TCTR20221001004 .

Purpose: The COVID-19 pandemic has affected public health worldwide. The efficacy and safety of COVID-19 vaccines have been evaluated in the general population; however, data on patients with malignancies are limited. Methods: This prospective longitudinal observational cohort study was conducted between June and July 2021. Enrolled adult patients with cancer were divided into chemotherapy and nonchemotherapy groups. All participants were immunized with two doses of the ChAdOx1 nCoV-19 or CoronaVac COVID-19 vaccines. The primary outcome was a comparison of the immunogenicity (as assessed by spike protein [anti-S] immunoglobulin G [IgG] antibody titers) of two doses of COVID-19 vaccine in the chemotherapy and nonchemotherapy groups. The secondary outcomes included the anti-S IgG seroconversion rate and vaccine safety in both groups. Results: Among the 173 enrolled patients with solid cancer, after COVID-19 vaccination, the chemotherapy group had a significantly lower median anti-S IgG titer than the nonchemotherapy group (26 v 237 U/mL, P < .001). A statistically significant difference in anti-S IgG titer was found between groups vaccinated with CoronaVac (7 v 90 U/mL, P < .001), but no difference was found in those vaccinated with ChAdOx1 nCoV-19 (818 v 1061 U/mL, P = .075). The anti-S IgG seroconversion rate was significantly lower in the chemotherapy group than that in the nonchemotherapy group (78.9% v 96.5%, P = .001). No new or serious vaccine-related adverse events were reported. Conclusion: Patients with solid cancer receiving a COVID-19 vaccine while undergoing chemotherapy had lower immunogenicity responses to vaccination than those who were vaccinated while undergoing nonchemotherapy treatment. No statistically significant difference was observed in the COVID-19 vaccine safety profiles between groups.

Introduction Cancer patients are more vulnerable to coronavirus disease 2019 (COVID-19) owing to their compromised immune status. However, data regarding COVID-19 vaccine safety and immune response in cancer patients are scarce. Method This prospective, age- and sex-matched, single-center cohort study included 61 cancer patients and 122 healthy control participants. Seropositivity was defined as anti-S IgG titer >0.8 units/ml. Primary end point was seroconversion rate of immunoglobulin (Ig)G antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein (anti-S IgG) in cancer patients vs. healthy control participants following the second dose of COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results After the second-dose vaccination, there was no difference in seropositivity rate between groups (57 [93.44%] patients with cancer vs. 121 [99.18%] control participants; geometric mean ratio [GMR]: 0.39; 95%CI: 0.01–10.46; p-value = 0.571). In contrast, after the first-dose vaccination, the seropositivity rate was significantly lower in the cancer patients than in the control participants (50/61 [81.97%] vs. 121/122 [99.18%]; GMR: 0.07; 95%CI: 0.01–0.71; p = 0.025). The median anti-S IgG titer after the first-and second dose vaccination were not significantly different between groups. Female sex was significantly associated with a higher anti-S IgG titer. 5FU- and taxane-based chemotherapy regimens were associated with a lower IgG titer. Side effects of vaccination were tolerable. Conclusions The anti-S IgG seropositivity rate after completing the second vaccine dose did not differ between the cancer patients and control participants. However, the anti-S IgG seropositivity rate after the first-dose vaccination was lower in cancer patients.