Key clinical point: Artificial intelligence (AI) shows high sensitivity, specificity, and accuracy for the diagnosis of early gastric cancer.

Major finding: The pooled sensitivity and specificity of AI for early gastric cancer diagnosis were 0.86 and 0.90, respectively. The accuracy of AI was 0.94. The pooled sensitivity and specificity of deep learning methods were 0.84 and 0.88, respectively, and those of nondeep learning methods were 0.91 and 0.90, respectively. The accuracy of the nondeep learning methods was higher compared with the deep learning methods (0.96 vs. 0.93).

Study details: This meta-analysis of 12 retrospective case-control studies (n = 11,685) assessed the performance of AI in the endoscopic diagnosis of early gastric cancer.

Disclosures: No funding source was identified for this study. The authors declared no conflicts of interest.

Source: Chen P-C et al. The accuracy of artificial intelligence in the endoscopic diagnosis of early gastric cancer: Pooled Analysis Study. J Med Internet Res. 2022;24(5):e27694 (May 16). Doi: 10.2196/27694

Key clinical point: Artificial intelligence (AI) shows high sensitivity, specificity, and accuracy for the diagnosis of early gastric cancer.

Major finding: The pooled sensitivity and specificity of AI for early gastric cancer diagnosis were 0.86 and 0.90, respectively. The accuracy of AI was 0.94. The pooled sensitivity and specificity of deep learning methods were 0.84 and 0.88, respectively, and those of nondeep learning methods were 0.91 and 0.90, respectively. The accuracy of the nondeep learning methods was higher compared with the deep learning methods (0.96 vs. 0.93).

Study details: This meta-analysis of 12 retrospective case-control studies (n = 11,685) assessed the performance of AI in the endoscopic diagnosis of early gastric cancer.

Disclosures: No funding source was identified for this study. The authors declared no conflicts of interest.

Source: Chen P-C et al. The accuracy of artificial intelligence in the endoscopic diagnosis of early gastric cancer: Pooled Analysis Study. J Med Internet Res. 2022;24(5):e27694 (May 16). Doi: 10.2196/27694

Key clinical point: Artificial intelligence (AI) shows high sensitivity, specificity, and accuracy for the diagnosis of early gastric cancer.

Major finding: The pooled sensitivity and specificity of AI for early gastric cancer diagnosis were 0.86 and 0.90, respectively. The accuracy of AI was 0.94. The pooled sensitivity and specificity of deep learning methods were 0.84 and 0.88, respectively, and those of nondeep learning methods were 0.91 and 0.90, respectively. The accuracy of the nondeep learning methods was higher compared with the deep learning methods (0.96 vs. 0.93).

Study details: This meta-analysis of 12 retrospective case-control studies (n = 11,685) assessed the performance of AI in the endoscopic diagnosis of early gastric cancer.

Disclosures: No funding source was identified for this study. The authors declared no conflicts of interest.

Source: Chen P-C et al. The accuracy of artificial intelligence in the endoscopic diagnosis of early gastric cancer: Pooled Analysis Study. J Med Internet Res. 2022;24(5):e27694 (May 16). Doi: 10.2196/27694

Key clinical point: There is no improvement in survival of patients with nonmetastatic gastric adenocarcinoma in selected European countries. The survival has slightly improved in the US and worsened in Sweden.

Major finding: The overall survival (OS) trend improved in the US (hazard ratio [HR] per year 0.99) and worsened in Sweden (HR per year 1.03). There was no improvement in OS trend in the Netherlands, Belgium, Norway, and Slovenia. After adjusting for resection, the OS trend became insignificant in Sweden and improved in the US, Slovenia, and Norway.

Study details: A real-world observational study of individual-level data of 66,398 patients diagnosed with nonmetastatic gastric adenocarcinoma during 2003-2016 in the US and 5 European countries.

Disclosures: This study was supported by Deutsche Krebshilfe. The authors declared no competing interests.

Source: Huang L et al. Survival trends of patients with non-metastatic gastric adenocarcinoma in the US and European countries: The impact of decreasing resection rates. Cancer Commun (Lond). 2022 (Jun 6). Doi: 10.1002/cac2.12318

Key clinical point: There is no improvement in survival of patients with nonmetastatic gastric adenocarcinoma in selected European countries. The survival has slightly improved in the US and worsened in Sweden.

Major finding: The overall survival (OS) trend improved in the US (hazard ratio [HR] per year 0.99) and worsened in Sweden (HR per year 1.03). There was no improvement in OS trend in the Netherlands, Belgium, Norway, and Slovenia. After adjusting for resection, the OS trend became insignificant in Sweden and improved in the US, Slovenia, and Norway.

Study details: A real-world observational study of individual-level data of 66,398 patients diagnosed with nonmetastatic gastric adenocarcinoma during 2003-2016 in the US and 5 European countries.

Disclosures: This study was supported by Deutsche Krebshilfe. The authors declared no competing interests.

Source: Huang L et al. Survival trends of patients with non-metastatic gastric adenocarcinoma in the US and European countries: The impact of decreasing resection rates. Cancer Commun (Lond). 2022 (Jun 6). Doi: 10.1002/cac2.12318

Key clinical point: There is no improvement in survival of patients with nonmetastatic gastric adenocarcinoma in selected European countries. The survival has slightly improved in the US and worsened in Sweden.

Major finding: The overall survival (OS) trend improved in the US (hazard ratio [HR] per year 0.99) and worsened in Sweden (HR per year 1.03). There was no improvement in OS trend in the Netherlands, Belgium, Norway, and Slovenia. After adjusting for resection, the OS trend became insignificant in Sweden and improved in the US, Slovenia, and Norway.

Study details: A real-world observational study of individual-level data of 66,398 patients diagnosed with nonmetastatic gastric adenocarcinoma during 2003-2016 in the US and 5 European countries.

Disclosures: This study was supported by Deutsche Krebshilfe. The authors declared no competing interests.

Source: Huang L et al. Survival trends of patients with non-metastatic gastric adenocarcinoma in the US and European countries: The impact of decreasing resection rates. Cancer Commun (Lond). 2022 (Jun 6). Doi: 10.1002/cac2.12318

Takeaway: Laparoscopic vs. open gastrectomy (LG vs. OG) is associated with a lower complication rate and higher survival in elderly patients (age ≥ 80 years) with gastric cancer.

Major finding: Elderly patients who received LG vs. OG had lower blood loss (40 vs. 240 g; P < .01) and incidence of overall postoperative complications (29% vs. 53%; P < .05). The 5-year disease-specific survival rate was significantly higher in the LG vs. OG elderly group (93% vs. 78%; P < .05). Elderly vs. nonelderly patients who received LG had a significantly lower 5-year overall survival rate (67% vs. 87%; P < .01).

Study details: This retrospective study included patients with gastric cancer who received curative gastrectomy between 2003 and 2015 and were divided into three groups, elderly patients who received LG (n = 45) and OG (n = 43) and nonelderly patients who received LG (n = 329).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Ueda Y et al. Technical and oncological safety of laparoscopic gastrectomy for gastric cancer in elderly patients ≥ 80 years old. BMC Geriatr. 2022;22:475 (Jun 2). Doi: 10.1186/s12877-022-03180-7

Takeaway: Laparoscopic vs. open gastrectomy (LG vs. OG) is associated with a lower complication rate and higher survival in elderly patients (age ≥ 80 years) with gastric cancer.

Major finding: Elderly patients who received LG vs. OG had lower blood loss (40 vs. 240 g; P < .01) and incidence of overall postoperative complications (29% vs. 53%; P < .05). The 5-year disease-specific survival rate was significantly higher in the LG vs. OG elderly group (93% vs. 78%; P < .05). Elderly vs. nonelderly patients who received LG had a significantly lower 5-year overall survival rate (67% vs. 87%; P < .01).

Study details: This retrospective study included patients with gastric cancer who received curative gastrectomy between 2003 and 2015 and were divided into three groups, elderly patients who received LG (n = 45) and OG (n = 43) and nonelderly patients who received LG (n = 329).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Ueda Y et al. Technical and oncological safety of laparoscopic gastrectomy for gastric cancer in elderly patients ≥ 80 years old. BMC Geriatr. 2022;22:475 (Jun 2). Doi: 10.1186/s12877-022-03180-7

Takeaway: Laparoscopic vs. open gastrectomy (LG vs. OG) is associated with a lower complication rate and higher survival in elderly patients (age ≥ 80 years) with gastric cancer.

Major finding: Elderly patients who received LG vs. OG had lower blood loss (40 vs. 240 g; P < .01) and incidence of overall postoperative complications (29% vs. 53%; P < .05). The 5-year disease-specific survival rate was significantly higher in the LG vs. OG elderly group (93% vs. 78%; P < .05). Elderly vs. nonelderly patients who received LG had a significantly lower 5-year overall survival rate (67% vs. 87%; P < .01).

Study details: This retrospective study included patients with gastric cancer who received curative gastrectomy between 2003 and 2015 and were divided into three groups, elderly patients who received LG (n = 45) and OG (n = 43) and nonelderly patients who received LG (n = 329).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Ueda Y et al. Technical and oncological safety of laparoscopic gastrectomy for gastric cancer in elderly patients ≥ 80 years old. BMC Geriatr. 2022;22:475 (Jun 2). Doi: 10.1186/s12877-022-03180-7

Key clinical point: Epstein-Barr virus (EBV) and Helicobacter pylori coinfection is not an independent prognostic factor for gastric cancer. EBV infection was associated with survival, but not in patients with non-gastric carcinoma with lymphoid stroma (non-GCLS).

Major finding: EBV infection alone (hazard ratio 0.362; P = .049) showed an inverse correlation with overall survival (OS). The 5-year OS rate was not significantly different between the EBV and H. pylori coinfection vs. other groups (97.6% vs. 86.8%; P = .144). In patients with non-GCLS, the OS rate was not significantly different between the EBV-positive vs. other groups (96.9% vs. 86.4%; P = .126).

Study details: This retrospective study included 956 patients with gastric cancer who underwent surgery between September 2014 and August 2015 and were subdivided into groups according to the GCLS morphology and EBV and H. pylori infection statuses.

Disclosures: No funding source was identified for this study. Dr. JY Ahn is an editorial board member of the journal. The other authors reported no conflicts of interest.

Source: Noh JH et al. Clinical significance of Epstein-Barr virus and Helicobacter pylori infection in gastric carcinoma. Gut Liver. 2022 (May 25). Doi: 10.5009/gnl210593

Key clinical point: Epstein-Barr virus (EBV) and Helicobacter pylori coinfection is not an independent prognostic factor for gastric cancer. EBV infection was associated with survival, but not in patients with non-gastric carcinoma with lymphoid stroma (non-GCLS).

Major finding: EBV infection alone (hazard ratio 0.362; P = .049) showed an inverse correlation with overall survival (OS). The 5-year OS rate was not significantly different between the EBV and H. pylori coinfection vs. other groups (97.6% vs. 86.8%; P = .144). In patients with non-GCLS, the OS rate was not significantly different between the EBV-positive vs. other groups (96.9% vs. 86.4%; P = .126).

Study details: This retrospective study included 956 patients with gastric cancer who underwent surgery between September 2014 and August 2015 and were subdivided into groups according to the GCLS morphology and EBV and H. pylori infection statuses.

Disclosures: No funding source was identified for this study. Dr. JY Ahn is an editorial board member of the journal. The other authors reported no conflicts of interest.

Source: Noh JH et al. Clinical significance of Epstein-Barr virus and Helicobacter pylori infection in gastric carcinoma. Gut Liver. 2022 (May 25). Doi: 10.5009/gnl210593

Key clinical point: Epstein-Barr virus (EBV) and Helicobacter pylori coinfection is not an independent prognostic factor for gastric cancer. EBV infection was associated with survival, but not in patients with non-gastric carcinoma with lymphoid stroma (non-GCLS).

Major finding: EBV infection alone (hazard ratio 0.362; P = .049) showed an inverse correlation with overall survival (OS). The 5-year OS rate was not significantly different between the EBV and H. pylori coinfection vs. other groups (97.6% vs. 86.8%; P = .144). In patients with non-GCLS, the OS rate was not significantly different between the EBV-positive vs. other groups (96.9% vs. 86.4%; P = .126).

Study details: This retrospective study included 956 patients with gastric cancer who underwent surgery between September 2014 and August 2015 and were subdivided into groups according to the GCLS morphology and EBV and H. pylori infection statuses.

Disclosures: No funding source was identified for this study. Dr. JY Ahn is an editorial board member of the journal. The other authors reported no conflicts of interest.

Source: Noh JH et al. Clinical significance of Epstein-Barr virus and Helicobacter pylori infection in gastric carcinoma. Gut Liver. 2022 (May 25). Doi: 10.5009/gnl210593

Key clinical point: In older patients with potentially resectable gastric cancer, gastrectomy vs. conservative treatment may improve survival. The minimally invasive approach has fewer complications and extended lymphadenectomy may have survival benefit.

Major finding: Gastrectomy vs. conservative treatment improved overall survival in all six studies included in the analysis, but study quality was low and meta-analysis was not feasible. Minimally invasive vs. open gastrectomy was associated with fewer complications (pooled risk ratio 0.71; P = .005) and similar OS (P = .58). Extended vs. limited lymphadenectomy prolonged OS or cancer-specific survival in two cohort studies, with similar complication rates.

Study details: This systematic review of 31 studies included patients aged ≥ 70 years with potentially resectable stage I-III gastric cancer.

Disclosures: This study had no sponsors. The authors declared no conflicts of interest.

Source: Argillander TE et al. Outcomes of surgical treatment of non-metastatic gastric cancer in patients aged 70 and older: A systematic review and meta-analysis. Eur J Surg Oncol. 2022 (May 16). Doi: 10.1016/j.ejso.2022.05.003

Key clinical point: In older patients with potentially resectable gastric cancer, gastrectomy vs. conservative treatment may improve survival. The minimally invasive approach has fewer complications and extended lymphadenectomy may have survival benefit.

Major finding: Gastrectomy vs. conservative treatment improved overall survival in all six studies included in the analysis, but study quality was low and meta-analysis was not feasible. Minimally invasive vs. open gastrectomy was associated with fewer complications (pooled risk ratio 0.71; P = .005) and similar OS (P = .58). Extended vs. limited lymphadenectomy prolonged OS or cancer-specific survival in two cohort studies, with similar complication rates.

Study details: This systematic review of 31 studies included patients aged ≥ 70 years with potentially resectable stage I-III gastric cancer.

Disclosures: This study had no sponsors. The authors declared no conflicts of interest.

Source: Argillander TE et al. Outcomes of surgical treatment of non-metastatic gastric cancer in patients aged 70 and older: A systematic review and meta-analysis. Eur J Surg Oncol. 2022 (May 16). Doi: 10.1016/j.ejso.2022.05.003

Key clinical point: In older patients with potentially resectable gastric cancer, gastrectomy vs. conservative treatment may improve survival. The minimally invasive approach has fewer complications and extended lymphadenectomy may have survival benefit.

Major finding: Gastrectomy vs. conservative treatment improved overall survival in all six studies included in the analysis, but study quality was low and meta-analysis was not feasible. Minimally invasive vs. open gastrectomy was associated with fewer complications (pooled risk ratio 0.71; P = .005) and similar OS (P = .58). Extended vs. limited lymphadenectomy prolonged OS or cancer-specific survival in two cohort studies, with similar complication rates.

Study details: This systematic review of 31 studies included patients aged ≥ 70 years with potentially resectable stage I-III gastric cancer.

Disclosures: This study had no sponsors. The authors declared no conflicts of interest.

Source: Argillander TE et al. Outcomes of surgical treatment of non-metastatic gastric cancer in patients aged 70 and older: A systematic review and meta-analysis. Eur J Surg Oncol. 2022 (May 16). Doi: 10.1016/j.ejso.2022.05.003

Key clinical point: Pretreatment CD163+ macrophage infiltration is a prognostic biomarker in patients with metastatic gastric cancer.

Major finding: The median overall survival (OS) was significantly longer in patients who underwent vs. did not undergo conversion surgery after induction chemotherapy (33.3 vs. 9.0 months; P < .0001). Overall, the median OS in the CD163-low vs. -high group was not reached vs. 16.8 months, respectively (P < .001). In patients who underwent conversion surgery, the median OS in the CD163-low vs. -high group was not reached vs. 24.8 months, respectively (P = .020).

Study details: This retrospective study evaluated the numbers of tumor-infiltrating CD4+, CD8+, and Foxp3+ lymphocytes and CD68+ and CD163+ macrophages in pretreatment endoscopic biopsy samples of 68 patients with metastatic gastric cancer who received induction chemotherapy (docetaxel plus cisplatin plus S-1) with or without conversion surgery between April 2006 and March 2019.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kinoshita J et al. Prognostic value of tumor-infiltrating CD163+macrophage in patients with metastatic gastric cancer undergoing multidisciplinary treatment. BMC Cancer. 2022;22:608 (Jun 3). Doi: 10.1186/s12885-022-09713-y

Key clinical point: Pretreatment CD163+ macrophage infiltration is a prognostic biomarker in patients with metastatic gastric cancer.

Major finding: The median overall survival (OS) was significantly longer in patients who underwent vs. did not undergo conversion surgery after induction chemotherapy (33.3 vs. 9.0 months; P < .0001). Overall, the median OS in the CD163-low vs. -high group was not reached vs. 16.8 months, respectively (P < .001). In patients who underwent conversion surgery, the median OS in the CD163-low vs. -high group was not reached vs. 24.8 months, respectively (P = .020).

Study details: This retrospective study evaluated the numbers of tumor-infiltrating CD4+, CD8+, and Foxp3+ lymphocytes and CD68+ and CD163+ macrophages in pretreatment endoscopic biopsy samples of 68 patients with metastatic gastric cancer who received induction chemotherapy (docetaxel plus cisplatin plus S-1) with or without conversion surgery between April 2006 and March 2019.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kinoshita J et al. Prognostic value of tumor-infiltrating CD163+macrophage in patients with metastatic gastric cancer undergoing multidisciplinary treatment. BMC Cancer. 2022;22:608 (Jun 3). Doi: 10.1186/s12885-022-09713-y

Key clinical point: Pretreatment CD163+ macrophage infiltration is a prognostic biomarker in patients with metastatic gastric cancer.

Major finding: The median overall survival (OS) was significantly longer in patients who underwent vs. did not undergo conversion surgery after induction chemotherapy (33.3 vs. 9.0 months; P < .0001). Overall, the median OS in the CD163-low vs. -high group was not reached vs. 16.8 months, respectively (P < .001). In patients who underwent conversion surgery, the median OS in the CD163-low vs. -high group was not reached vs. 24.8 months, respectively (P = .020).

Study details: This retrospective study evaluated the numbers of tumor-infiltrating CD4+, CD8+, and Foxp3+ lymphocytes and CD68+ and CD163+ macrophages in pretreatment endoscopic biopsy samples of 68 patients with metastatic gastric cancer who received induction chemotherapy (docetaxel plus cisplatin plus S-1) with or without conversion surgery between April 2006 and March 2019.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kinoshita J et al. Prognostic value of tumor-infiltrating CD163+macrophage in patients with metastatic gastric cancer undergoing multidisciplinary treatment. BMC Cancer. 2022;22:608 (Jun 3). Doi: 10.1186/s12885-022-09713-y

Key clinical point: Regular tea consumption shows a weak inverse association with risk for gastric cancer.

Major finding: Regular vs. nonregular tea drinkers had a significantly lower risk for gastric cancer (pooled odds ratio [OR] 0.91; 95% CI 0.85-0.97). Compared with nonregular tea drinkers, there was no difference in risk for gastric cancer in regular tea drinkers who consumed 1 to <2, 2 to <3, ≥3 cups (P_trend = .27). A lower risk was observed in studies from China, Japan, and Iran (OR 0.62; 95% CI 0.48-0.81) and from China and Japan (OR 0.67; 95% CI  0.49-0.91).

Study details: A pooled analysis of 34 studies including 13,121 patients with gastric cancer and 31,420 control individuals from the StoP Project (a consortium of epidemiological studies on gastric cancer) dataset.

Disclosures: This study was supported by Associazione Italiana per la Ricerca sul Cancro and Italian League for the Fight Against Cancer. The authors declared no competing interests.

Source: Martimianaki G et al. Tea consumption and gastric cancer: A pooled analysis from the Stomach cancer Pooling (StoP) Project consortium. Br J Cancer. 2022 (May 24). Doi: 10.1038/s41416-022-01856-w

Key clinical point: Regular tea consumption shows a weak inverse association with risk for gastric cancer.

Major finding: Regular vs. nonregular tea drinkers had a significantly lower risk for gastric cancer (pooled odds ratio [OR] 0.91; 95% CI 0.85-0.97). Compared with nonregular tea drinkers, there was no difference in risk for gastric cancer in regular tea drinkers who consumed 1 to <2, 2 to <3, ≥3 cups (P_trend = .27). A lower risk was observed in studies from China, Japan, and Iran (OR 0.62; 95% CI 0.48-0.81) and from China and Japan (OR 0.67; 95% CI  0.49-0.91).

Study details: A pooled analysis of 34 studies including 13,121 patients with gastric cancer and 31,420 control individuals from the StoP Project (a consortium of epidemiological studies on gastric cancer) dataset.

Disclosures: This study was supported by Associazione Italiana per la Ricerca sul Cancro and Italian League for the Fight Against Cancer. The authors declared no competing interests.

Source: Martimianaki G et al. Tea consumption and gastric cancer: A pooled analysis from the Stomach cancer Pooling (StoP) Project consortium. Br J Cancer. 2022 (May 24). Doi: 10.1038/s41416-022-01856-w

Key clinical point: Regular tea consumption shows a weak inverse association with risk for gastric cancer.

Major finding: Regular vs. nonregular tea drinkers had a significantly lower risk for gastric cancer (pooled odds ratio [OR] 0.91; 95% CI 0.85-0.97). Compared with nonregular tea drinkers, there was no difference in risk for gastric cancer in regular tea drinkers who consumed 1 to <2, 2 to <3, ≥3 cups (P_trend = .27). A lower risk was observed in studies from China, Japan, and Iran (OR 0.62; 95% CI 0.48-0.81) and from China and Japan (OR 0.67; 95% CI  0.49-0.91).

Study details: A pooled analysis of 34 studies including 13,121 patients with gastric cancer and 31,420 control individuals from the StoP Project (a consortium of epidemiological studies on gastric cancer) dataset.

Disclosures: This study was supported by Associazione Italiana per la Ricerca sul Cancro and Italian League for the Fight Against Cancer. The authors declared no competing interests.

Source: Martimianaki G et al. Tea consumption and gastric cancer: A pooled analysis from the Stomach cancer Pooling (StoP) Project consortium. Br J Cancer. 2022 (May 24). Doi: 10.1038/s41416-022-01856-w

Key clinical point: High tumor mutational burden (TMB) is associated with clinical outcomes with pembrolizumab with or without chemotherapy in patients with gastric/gastroesophageal junction adenocarcinoma.

Major finding: In patients with high TMB, pembrolizumab vs. chemotherapy significantly improved the objective response rate (ORR; 55.6% vs. 41.2%), progression-free survival (PFS; hazard ratio [HR] 0.52), and overall survival (OS; HR 0.34). Similarly, pembrolizumab plus chemotherapy vs. chemotherapy improved ORR (73.3% vs. 41.2%), PFS (HR 0.62), and OS (HR 0.54) in patients with high TMB.

Study details: This prespecified exploratory analysis of phase 3 KEYNOTE-062 study included patients with gastric cancer who were randomly assigned (1:1:1) to receive pembrolizumab, pembrolizumab plus chemotherapy, or placebo plus chemotherapy.

Disclosures: This study was funded by Merck Sharp and Dohme LLC. The authors declared receiving grants, personal or advisory fees, or nonfinancial support. Some authors declared owing stocks or being cofounders or employees in various companies.

Source: Lee K-W et al. Association of tumor mutational burden with efficacy of pembrolizumab ± chemotherapy as first-line therapy for gastric cancer in the phase III KEYNOTE-062 study. Clin Cancer Res. 2022 (Jun 3). Doi: 10.1158/1078-0432.CCR-22-0121

Key clinical point: High tumor mutational burden (TMB) is associated with clinical outcomes with pembrolizumab with or without chemotherapy in patients with gastric/gastroesophageal junction adenocarcinoma.

Major finding: In patients with high TMB, pembrolizumab vs. chemotherapy significantly improved the objective response rate (ORR; 55.6% vs. 41.2%), progression-free survival (PFS; hazard ratio [HR] 0.52), and overall survival (OS; HR 0.34). Similarly, pembrolizumab plus chemotherapy vs. chemotherapy improved ORR (73.3% vs. 41.2%), PFS (HR 0.62), and OS (HR 0.54) in patients with high TMB.

Study details: This prespecified exploratory analysis of phase 3 KEYNOTE-062 study included patients with gastric cancer who were randomly assigned (1:1:1) to receive pembrolizumab, pembrolizumab plus chemotherapy, or placebo plus chemotherapy.

Disclosures: This study was funded by Merck Sharp and Dohme LLC. The authors declared receiving grants, personal or advisory fees, or nonfinancial support. Some authors declared owing stocks or being cofounders or employees in various companies.

Source: Lee K-W et al. Association of tumor mutational burden with efficacy of pembrolizumab ± chemotherapy as first-line therapy for gastric cancer in the phase III KEYNOTE-062 study. Clin Cancer Res. 2022 (Jun 3). Doi: 10.1158/1078-0432.CCR-22-0121

Key clinical point: High tumor mutational burden (TMB) is associated with clinical outcomes with pembrolizumab with or without chemotherapy in patients with gastric/gastroesophageal junction adenocarcinoma.

Major finding: In patients with high TMB, pembrolizumab vs. chemotherapy significantly improved the objective response rate (ORR; 55.6% vs. 41.2%), progression-free survival (PFS; hazard ratio [HR] 0.52), and overall survival (OS; HR 0.34). Similarly, pembrolizumab plus chemotherapy vs. chemotherapy improved ORR (73.3% vs. 41.2%), PFS (HR 0.62), and OS (HR 0.54) in patients with high TMB.

Study details: This prespecified exploratory analysis of phase 3 KEYNOTE-062 study included patients with gastric cancer who were randomly assigned (1:1:1) to receive pembrolizumab, pembrolizumab plus chemotherapy, or placebo plus chemotherapy.

Disclosures: This study was funded by Merck Sharp and Dohme LLC. The authors declared receiving grants, personal or advisory fees, or nonfinancial support. Some authors declared owing stocks or being cofounders or employees in various companies.

Source: Lee K-W et al. Association of tumor mutational burden with efficacy of pembrolizumab ± chemotherapy as first-line therapy for gastric cancer in the phase III KEYNOTE-062 study. Clin Cancer Res. 2022 (Jun 3). Doi: 10.1158/1078-0432.CCR-22-0121

Key clinical point: Ramucirumab in combination with irinotecan fails to improve the progression-free survival (PFS) rate at 6 months in patients with previously treated advanced gastric cancer.

Major finding: The 6-month PFS rate was 26.5% (P = .1353). The median PFS was 4.2 months, and the median overall survival was 9.6 months. The most common grade ≥3 adverse events were neutropenia (51%), leucopenia (43%), anemia (20%), anorexia (14%), and febrile neutropenia (11%). There were no treatment-related deaths or new safety signals.

Study details: This study was a single-arm, phase 2 multicenter trial of 35 patients (HGCSG 1603)  with previously treated advanced gastric cancer who received the second-line ramucirumab plus irinotecan. The primary endpoint was the 6-month PFS rate.

Disclosures: This study was supported by Eli Lilly Japan K.K.  Several of the authors received honoraria or research funding or declared ownership interests outside this work, including with Eli Lilly Japan.

Source: Kawamoto Y et al. Phase II study of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with advanced gastric cancer: HGCSG1603. Oncologist. 2022 (May 17). Doi: 10.1093/oncolo/oyac086

Key clinical point: Ramucirumab in combination with irinotecan fails to improve the progression-free survival (PFS) rate at 6 months in patients with previously treated advanced gastric cancer.

Major finding: The 6-month PFS rate was 26.5% (P = .1353). The median PFS was 4.2 months, and the median overall survival was 9.6 months. The most common grade ≥3 adverse events were neutropenia (51%), leucopenia (43%), anemia (20%), anorexia (14%), and febrile neutropenia (11%). There were no treatment-related deaths or new safety signals.

Study details: This study was a single-arm, phase 2 multicenter trial of 35 patients (HGCSG 1603)  with previously treated advanced gastric cancer who received the second-line ramucirumab plus irinotecan. The primary endpoint was the 6-month PFS rate.

Disclosures: This study was supported by Eli Lilly Japan K.K.  Several of the authors received honoraria or research funding or declared ownership interests outside this work, including with Eli Lilly Japan.

Source: Kawamoto Y et al. Phase II study of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with advanced gastric cancer: HGCSG1603. Oncologist. 2022 (May 17). Doi: 10.1093/oncolo/oyac086

Key clinical point: Ramucirumab in combination with irinotecan fails to improve the progression-free survival (PFS) rate at 6 months in patients with previously treated advanced gastric cancer.

Major finding: The 6-month PFS rate was 26.5% (P = .1353). The median PFS was 4.2 months, and the median overall survival was 9.6 months. The most common grade ≥3 adverse events were neutropenia (51%), leucopenia (43%), anemia (20%), anorexia (14%), and febrile neutropenia (11%). There were no treatment-related deaths or new safety signals.

Study details: This study was a single-arm, phase 2 multicenter trial of 35 patients (HGCSG 1603)  with previously treated advanced gastric cancer who received the second-line ramucirumab plus irinotecan. The primary endpoint was the 6-month PFS rate.

Disclosures: This study was supported by Eli Lilly Japan K.K.  Several of the authors received honoraria or research funding or declared ownership interests outside this work, including with Eli Lilly Japan.

Source: Kawamoto Y et al. Phase II study of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with advanced gastric cancer: HGCSG1603. Oncologist. 2022 (May 17). Doi: 10.1093/oncolo/oyac086

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

A version of this article first appeared on Medscape.com.

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

A version of this article first appeared on Medscape.com.

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

A version of this article first appeared on Medscape.com.