World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Letter to the Editor

Volume 14, Number 4, August 2023, pages 316-320

The Effect of mRNA-Based COVID-19 Vaccination on Anti-Programmed Cell Death Protein 1 Blockade for Nasopharyngeal Cancer May Differ From a Virus-Inactivated Vaccine

**Table 1.** Clinical Characteristics of the NPC Patient Cohort
Tumor type	Study	Administration group	Cases	Median (95% CI) (months)	Hazard ratio (95% CI)
^aThe ONO-4538-11/CA209141 study was also reported as the CHECKMATE-141 study. COVID-19: coronavirus disease 2019; NPC: nasopharyngeal cancer; HPV: human papillomavirus; DOR: duration of response; ORR: overall response rate; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; Vac.: vaccine; CI: confidence interval; NA: not available.
Recurrent/metastatic nasopharyngeal cancer in Japanese	ONO-4538-11/CA209141 study^a	Methotrexate, docetaxel or cetuximab	9 (Japanese)	6.2 (5.2 - 6.8)	0.71 (0.42 - 1.19)
		Nivolumab	18 (Japanese)	8.8 (7.3 - 9.5)
	Our clinical research	In COVID-19 era, January 2021 - November 2022 (%)
		Age, years	Total 106	65.8 (62 - 72)
		Gender		Male 88/female 18
		HPV test-positive		Male 37 (42.0)/female 6 (33.3)
		Treatment method	Result of treatment
			DOR (months)	ORR
		Methotrexate, docetaxel or cetuximab	4	6.7 (6.4 - 7.0)	PD 4 (100)
		Nivolumab	36	8.6 (6.5 - 9.6)	ORR: 11.1% (CR 2 (5.6), PR 2 (5.6), SD 8 (22.2), PD 24 (66.7))
		BNT162b2 mRNA Vac. + methotrexate, docetaxel or cetuximab	6	6.5 (5.2 - 7.6)	SD 2 (33.3), PD 4 (66.7)
		mRNA-1273 Vac. + methotrexate, docetaxel or cetuximab	6	NA	PD 6 (100)
		BNT162b2 mRNA Vac. + nivolumab	54	8.5 (6.8 - 9.4)	ORR: 11.1% (CR 2 (3.7), PR 4 (7.4), SD 8 (14.8), PD 40 (74.1))
		mRNA-1273 Vac + nivolumab	0	NA	NA

Table 1. Clinical Characteristics of the NPC Patient Cohort

Tumor type

Study

Administration group

Cases

Median (95% CI) (months)

Hazard ratio (95% CI)

^aThe ONO-4538-11/CA209141 study was also reported as the CHECKMATE-141 study. COVID-19: coronavirus disease 2019; NPC: nasopharyngeal cancer; HPV: human papillomavirus; DOR: duration of response; ORR: overall response rate; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; Vac.: vaccine; CI: confidence interval; NA: not available.

Recurrent/metastatic nasopharyngeal cancer in Japanese

ONO-4538-11/CA209141 study^a

Methotrexate, docetaxel or cetuximab

9 (Japanese)

6.2 (5.2 - 6.8)

0.71 (0.42 - 1.19)

Nivolumab

18 (Japanese)

8.8 (7.3 - 9.5)

Our clinical research

In COVID-19 era, January 2021 - November 2022 (%)

Age, years

Total 106

65.8 (62 - 72)

Gender

Male 88/female 18

HPV test-positive

Male 37 (42.0)/female 6 (33.3)

Treatment method

Result of treatment

DOR (months)

ORR

Methotrexate, docetaxel or cetuximab

6.7 (6.4 - 7.0)

PD 4 (100)

Nivolumab

8.6 (6.5 - 9.6)

ORR: 11.1% (CR 2 (5.6), PR 2 (5.6), SD 8 (22.2), PD 24 (66.7))

BNT162b2 mRNA Vac. + methotrexate, docetaxel or cetuximab

6.5 (5.2 - 7.6)

SD 2 (33.3), PD 4 (66.7)

mRNA-1273 Vac. + methotrexate, docetaxel or cetuximab

PD 6 (100)

BNT162b2 mRNA Vac. + nivolumab

8.5 (6.8 - 9.4)

ORR: 11.1% (CR 2 (3.7), PR 4 (7.4), SD 8 (14.8), PD 40 (74.1))

mRNA-1273 Vac + nivolumab

**Table 2.** HPV Test Positive Cases in Sub-Cohorts (ONO-4538-11/CA209141 Study)
HPV test	Treatment with nivolumab (n = 240)	Treatment without nivolumab (n = 121)
HPV: human papillomavirus; NA: not available.
Positive	63 (26.3%)	3 (16.7%)	29 (24.0%)	0
Negative	50 (20.8%)	0	36 (29.8%)	0
NA	127 (52.9%)	-	56 (46.3%)	-
No report	-	15 (83.3%)	-	9 (100.0%)

Table 2. HPV Test Positive Cases in Sub-Cohorts (ONO-4538-11/CA209141 Study)

HPV test

Treatment with nivolumab (n = 240)

Treatment without nivolumab (n = 121)

Total 240/Japanese 18 cases

Total 121/Japanese 9 cases

HPV: human papillomavirus; NA: not available.

Positive

63 (26.3%)

3 (16.7%)

29 (24.0%)

Negative

50 (20.8%)

36 (29.8%)

127 (52.9%)

56 (46.3%)

No report

15 (83.3%)

9 (100.0%)

**Table 3.** HPV Test Positive Cases in Sub-Cohorts (Our Clinical Research)
Tumor type	Treatment method	HPV test-positive cases, n (%)
HPV: human papillomavirus; Vac.: vaccine.
Recurrent/metastatic nasopharyngeal cancer in Japanese	Methotrexate, docetaxel or cetuximab (n = 4)	2 (50)
	Nivolumab (n = 36)	15 (41.67)
	BNT162b2 mRNA Vac. + methotrexate, docetaxel or cetuximab (n = 6)	2 (33.33)
	mRNA-1273 Vac. + methotrexate, docetaxel or cetuximab (n = 6)	2 (33.33)
	BNT162b2 mRNA Vac. + nivolumab (n = 54)	22 (40.74)
	mRNA-1273 Vac + nivolumab (n = 0)	0

Table 3. HPV Test Positive Cases in Sub-Cohorts (Our Clinical Research)

Tumor type

Treatment method

HPV test-positive cases, n (%)

Male 37 (42.0)/female 6 (33.3)

HPV: human papillomavirus; Vac.: vaccine.

Recurrent/metastatic nasopharyngeal cancer in Japanese

Methotrexate, docetaxel or cetuximab (n = 4)

2 (50)

Nivolumab (n = 36)

15 (41.67)

BNT162b2 mRNA Vac. + methotrexate, docetaxel or cetuximab (n = 6)

2 (33.33)

mRNA-1273 Vac. + methotrexate, docetaxel or cetuximab (n = 6)

2 (33.33)

BNT162b2 mRNA Vac. + nivolumab (n = 54)

22 (40.74)

mRNA-1273 Vac + nivolumab (n = 0)

**Table 4.** Clinical Side-Effects of the NPC Patient Cohort (Our Clinical Research)
Items	Nivolumab + vaccinated (n = 54), n (%)	Nivolumab (n = 36), n (%)	P value
ILD: interstitial lung disease; irAE: immune-related adverse event; RCCEP: reactive cutaneous capillary endothelial proliferation.
Side-effect of vaccination
Common side effects
Muscle pain	44 (81.5)	NA
Allergy	4 (7.4)	NA
Fever	6 (11.1)	NA
Nausea	4 (7.4)	NA
Headache	4 (7.4)	NA
Others	6 (11.1)	NA
irAE
Immune-related adverse effects	50 (92.6)	32 (88.9)	< 0.5
ILD	6 (11.1)	4 (11.1)
RCCEP	10 (25.9)	8 (22.2)
Hepatitis	6 (11.1)	2 (5.6)
Ulcerative colitis	8 (14.8)	6 (16.7)
Hypothyroidism	8 (14.8)	4 (11.1)
Others	6 (22.2)	4 (22.2)

Table 4. Clinical Side-Effects of the NPC Patient Cohort (Our Clinical Research)

Items

Nivolumab + vaccinated (n = 54), n (%)

Nivolumab (n = 36), n (%)

P value

ILD: interstitial lung disease; irAE: immune-related adverse event; RCCEP: reactive cutaneous capillary endothelial proliferation.

Side-effect of vaccination

Common side effects

Muscle pain

44 (81.5)

Allergy

4 (7.4)

Fever

6 (11.1)

Nausea

4 (7.4)

Headache

4 (7.4)

Others

6 (11.1)

irAE

Immune-related adverse effects

50 (92.6)

32 (88.9)

< 0.5

ILD

6 (11.1)

4 (11.1)

RCCEP

10 (25.9)

8 (22.2)

Hepatitis

6 (11.1)

2 (5.6)

Ulcerative colitis

8 (14.8)

6 (16.7)

Hypothyroidism

8 (14.8)

4 (11.1)

Others

6 (22.2)

4 (22.2)