Effectiveness and safety of COVID-19 vaccines in patients with oncological diseases: State-of-the-art

Table 1 Some of the more significant studies conducted on the efficacy and safety of COVID-19 vaccination with different approved COVID-19 vaccines in oncological patients with solid tumors

Ref.	Type of vaccine	Type of study	Subjects (diagnosis, other specific characteristics)	Data on efficacy	Data on safety (main side effects)
OnCovid study group[5]	NA	A multicenter observational registry-based study	All PTs included n = 2634 (100%); PTs with advanced tumor stage n = 1244 (46%); PTs with receipt of anti-cancer therapy within 4 wk of COVID-19 diagnosis n = 1305 (51.8%); malignancy type: Breast n = 493 (18.9%); gastrointestinal n = 476 (18.2%); gynecologic/genitourinary n = 530 (20.3%); hematologic n = 357 (13.7%)	The difference in the necessity of hospitalization due to COVID-19, oxygen therapy requirement, mechanical ventilation requirement, and 14-d CFR between PTs stratified across time five phases and two major outbreaks of the pandemic; hospitalization requirement: 1st phase-64.7% to 5th phase-42.7% (P < 0.01); proportion to PTs requiring oxygen: therapy, phase 1-62.6%, to phase 5-46.0% (P < 0.001); mechanical ventilation: Phase 1-12.1% to phase 5-11.8% (P = 0.01); CFR: 1st outbreak-25.6% to-2nd outbreak 16.2% (P < 0.001)	N/A
Khoury et al[63], 2021	mRNA and adenoviral vector vaccines			20.2% of subjects had (95%CI) 50% protective neutralization level	N/A
Monin et al[66], 2021	mRNA	Prospective observational study	PTs with oncologic disease n = 151: With solid cancer n = 95; with hematological malignancy n = 56; and HCs n = 54	Surrogate marker of efficiency: Seroconversion after 1st dose: 32 of 34 (94%) HCs, 21 of 56 (38%), PTs with solid cancer, 8 of 44 (18%) PTs with hematologic malignancies; after 2nd dose: 12 of 12 (100%) HCs; 18 of 19 (95%) PTs with solid, 3 of 5 (60%) PTs with hematologic malignancies	AE: Injection site pain within 7 d following the first dose in: 23 of 65 (35%) PTs with cancer; 12 of 25 (48%) HCs; no vaccine-related deaths were reported
Greenberger et al[69], 2021	mRNA and adenoviral vector vaccines	Retrospective cohort study	PTs with hematologic malignancies, n = 3300
Ehmsen et al[71], 2021	mRNA	Prospective cohort study (comparison between groups with different malignancies; no HCs)	PTs with cancer, n = 524, of whom: 201 (38%) with solid cancer; 323 (62%) with hematologic cancer; 524 (100%) had a blood sample drawn at a median of 36 d after the second dose of vaccine; and 247 (47%) had a second blood sample drawn 3 mo after the second dose of the vaccine	Seropositivity rate for anti-S IgG 36 d after vaccination: PTs with solid cancer 187 of 201 (93%); PTs with hematologic cancer 215 of 323 (66%); seropositivity rate for anti-S IgG 3 mo after vaccination: PTs with solid cancer-86%, PTs with hematologic cancer-53%; anti-S IgG titers; between 36-d and 3-mo samples declined from a median of 429 BAU/mL to a median of 139 BAU/mL (P = 0.03, Student’s t-test); T-cell reactivity: PTs with solid cancer-92 (46%), 70 (76%) mounted both CD4+ and CD8+ T-cell responses, 21 (23%) elicited only a CD8+ T-cell response, PTs with hematologic cancer-144 (45%), 81% were positive for both CD4+ and CD8+ T cells, 26 (18%) only elicited a CD8+ T cell response, 76% of the seronegative PTs did not elicit a T-cell response; PTs with solid cancer: only 1 of the 14 (7%) seronegative PTs elicited a T-cell response; PTs with hematologic cancer: 28 of 108 (26%) PTs elicited a T-cell response	N/A
Oosting et al[73], 2021	mRNA	Prospective, multicenter, non-inferiority trial	Cohort A: Individuals without cancer (control cohort); cohort B: PTs with SOTs, regardless of stage and histology, treated with immunotherapy; cohort C: PTs treated with chemotherapy; and cohort D: PTs treated with chemoimmunotherapy	Presence of SARS-CoV-2-binding antibodies after the second vaccination; at 28th d, 6 mo after 12 mo after a spike-specific T-cell response was defined as a two times or more significant increase in the number of spot-forming cells	N/A
Polack et al[84], 2020	mRNA vaccines	Placebo-controlled, observer-blinded, pivotal efficacy trial (randomized 1:1 vaccine vs placebo)	All PTs included n = 43548; PTs with liver disease n = 217 (0.6%)	95% efficacy (9 vaccinated vs 169 controls with COVID-19); 10 cases of severe COVID-19 infection vs 9 in the placebo group; flares: NR	Systemic AEs: (1) Fatigue (34%-51%); (2) headache (25%-39%); (3) fever (11%), injection site reactions; (4) pain (71%-83%); (5) redness and swelling (< 7%); and (6) serious AE < 4%
Fendler et al[67], 2021	BNT162b2 or AZD1222 vaccines (CAPTURE, NCT03226886)	Prospective cohort study	585 PTs, the seroconversion rates after two doses of BNT162b2 or AZD1222 vaccines given over 12 wk were assessed	After two doses of BNT162b2 or AZD1222 vaccines given over 12 wk, seroconversion was 85% and 59% in PTs with solid and hematological malignancies, respectively; vaccine-induced T-cell responses were found in 80% of PTs regardless of the vaccine or type of cancer	N/A
Goshen-Lago et al[75], 2021	BNT162b2 vaccine	Prospective study	154 PTs with SOTs and 135 HCs (health workers)	In PTs with cancer with active intravenous treatment, 79% (n = 122) of the PTs had positive serologic test results, compared with 84% (n = 114) in the control group; analysis by age, sex, or disease stage has no significant differences within the PT cohort; 15% of the seropositive PTs became seronegative after 6 mo, comparable to the control group	N/A
Waldhorn et al[76], 2021	BNT162b2 vaccine	Prospective study	154 PTs with SOTs and 135 controls	6 mo postvaccination, 79% of PTs and 84% of HCs were seropositive (P = 0.32); dramatically decreased serology titer
Shroff et al[78], 2021	BNT162b2	Phase 1 cohort trial	53 PTs with SOTs on active cytotoxic anticancer therapy and 50 healthy cohort	Neutralizing antibodies were detected in 67% of PTs with cancer after the first immunization, followed by a threefold increase in median titers after the second dose	AEs were mild: temperature, fever, headache, redness, and swelling on the injection site
Barrière et al[77], 2021	BNT162b2	VMO for vaccinated PTs under active treatment in the Department of Oncology of the Saint Jean Polyclinic, Nice, France	194 evaluable PTs with SOTs and 31 HCs	58 PTs had neutralizing antibodies, although the median levels were significantly lower than those in the control group; the data demonstrating impaired immunogenicity of the BNT162b2 vaccine in immunocompromised PTs; % of efficacy was not reported	N/A
Thomas et al[81], 2022	BNT162b2 mRNA	Phase 3 randomized clinical trial	3813 participants had a history of neoplasm: Most common malignancies were breast (n = 460), prostate (n = 362), and melanoma (n = 223)	Vaccine efficacy was 94.4% (95%CI) after up to 6 mo of follow-up post-dose 2	N/A
Wagner et al[79], 2022	mRNA-1273 or BNT162b2	Prospective, open-label, phase four trail	263 PTs with SOT, n = 63), MM, n = 70, IBD, n = 130 and 66 controls	1 mo after the two-dose primary vaccination, the highest nonresponder rate was found in MM PTs (17%); 6 mo after the second dose, 18% of PTs with MM, 10% with SOT, and 4% with IBD became seronegative compared to the control group; the vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2; booster vaccination increased antibody levels 8-fold in seropositive individuals and induced responses in those with undetectable pre-booster antibody levels	N/A
Lee et al[82], 2022	BNT162b2, ChAdOx1 nCov-19, or mixed and other	Population-based test-negative case-control study	Cancer cohort comprised 377194 individuals, of whom 42882 had breakthrough SARS-CoV-2 infections; the control population consisted of 28010955 individuals, of whom 5748708 had SARS-CoV-2 breakthrough infections	Overall vaccine effectiveness was 69.8% in the control population and 65.5% in the cancer cohort; vaccine effectiveness at 3-6 mo was lower in the cancer cohort (47.0%) than in the control population (61.4%)	N/A
Reimann et al[80], 2022	Ad26.COV2.S after BNT162b2 mRNA		32 oncological nonresponders to double-dose BNT162b2	The overall response rate was 31%	Mainly mild local and systemic reactions
Thakkar et al[83], 2023	Two doses of mRNA or one dose of AD26.CoV2.S vaccine and administered a third dose of mRNA vaccine	Single-arm prospective clinical trial	cancer PTs	A third dose of the COVID-19 vaccine induces durable immunity in cancer PTs, leading to seroconversion in 57% of PTs who did not respond to primary vaccination; 18 PTs with blood cancer and severe immune suppression had no response after three doses; and the fourth dose boosted the immune response by 2/3 of PTs, with neutralizing activity against the omicron variant	N/A

AE: Adverse event; CI: Confidence interval; CFR: Circulating free RNA; COVID 19: Coronavirus disease 2019; HCs; Healthy controls; IBD: Inflammatory bowel disease; MM: Multiple myeloma; NA: Not available; N/A: Not applicable; PT: Patient; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; SOT: Solid tumor; VMO: Vaccine monitoring observatory.