Vaccines in Cancer Care: Evidence, Guidelines & Clinical Considerations

Patients with cancer face a heightened risk of serious infections across the care continuum due to various factors, including chronic inflammation, impaired and/or decreased function of elements of the hematopoietic lineage and treatments that compromise immune function.^1,2 Infections in this population are associated with significant morbidity and mortality, and antimicrobial therapy is often less effective in these individuals than in people who are not immunocompromised. Preventive strategies, therefore, are central to supportive oncology care.¹

Immunization remains the most effective approach to preventing vaccine-preventable infections in the general population, yet its benefits are attenuated in immunocompromised patients. The ability to mount an adequate immune response is directly related to a patient’s net state of immunosuppression or severity of disease. As the degree of immunosuppression increases, the likelihood of an effective response to immunization decreases.¹

Patients with hematologic malignancies typically experience profound immune impairment, but those with solid tumors are also vulnerable due to factors such as debility, malnutrition and anatomic complications. Notably, the timing of vaccination is critical, as immunizations administered during chemotherapy or other periods of profound immunosuppression may be ineffective, and live vaccines may even cause vaccine-derived infections.¹

Despite these challenges, vaccination is a vital, if underutilized, component of supportive cancer care.³ As cancer therapies extend survival and enhance quality of life, preventive measures such as immunization should become integral to patient management.³ Clinical guidelines from the Infectious Diseases Society of America, the American Society of Clinical Oncology (ASCO) and the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) consistently recommend immunization of patients with cancer whenever possible and prioritize nonlive formulations, as live virus vaccines are typically contraindicated.¹ Notably, although nonlive vaccines are generally considered safe, their ability to produce immune responses may differ depending on the net state of immunosuppression of the patient.² For example, primary vaccinations against COVID-19 for patients with cancer have been found to generally produce lower antibody titers than in healthy individuals; however, booster doses can restore antibody titers in most patients to levels similar to those of healthy individuals, except in those undergoing B-cell-depleting therapy or cytotoxic chemotherapy. Importantly, even seronegative patients may generate T-cell responses to booster doses against COVID-19, which have appeared more durable than antibody responses.⁴

A comprehensive review of vaccination history at cancer diagnosis can help identify opportunities for early intervention and inform individualized immunization strategies. Alongside vaccines, adjunctive measures, including immune globulin administration and antiviral prophylaxis, may be necessary to provide adequate protection during periods of heightened vulnerability.

Taken together, vaccination represents an essential, though often underutilized, strategy to reduce infection-related morbidity and mortality in patients with cancer. Its integration into supportive oncology care warrants renewed emphasis.¹

The purpose of this literature review is to provide a synthesis of current evidence on immunization in patients with cancer, clarify evolving guideline recommendations and examine practical considerations for clinical integration. By aligning available data with best-practice guidance, this review aims to inform oncology care team members of strategies to optimize vaccine use, reduce infection-related morbidity and mortality and identify critical evidence gaps that warrant future investigation.

Overview of current literature and practices

The World Health Organization recommends vaccine coverage of at least 95% by age group with a somewhat lower goal of 75% coverage for influenza vaccination.⁵ Research has shown that people with solid and hematological cancer are at greater risk of contracting invasive pneumococcal disease (IPD) and other infectious diseases. A U.S. study showed that the incidence of invasive pneumococcal disease among adults with a solid tumor was 300.4 cases per 100,000 persons and among those with hematological cancers, 503.1 cases per 100,000 persons compared with 8.8 cases per 100,000 persons among healthy adults.⁶ A 2013 review found individuals with cancer had a 20.8% probability of hospitalization after experiencing an influenza infection compared with an 8.8% chance among the general population of people 65 years and older.⁷ Influenza-attributable mortality has been estimated at 11% to 33% among individuals with cancer.⁸

A number of factors influence immunosuppression among cancer patients; these include age, the type of cancer and the treatment regimen. When cancer treatment causes immunosuppression, lower levels of T and B cells may linger for months after treatment. To address these risks, French health authorities issued vaccination guidelines for immunocompromised patients. Diphtheria-tetanus-poliomyelitis and hepatitis B virus vaccinations are recommended for the general population, with booster doses specifically advised three months after chemotherapy completion for patients with solid tumors and six months after chemotherapy for those with hematologic malignancies who have additional treatment that is associated with immunosuppression.⁵ Pneumococcal vaccination starts with administration of the 13-valent pneumococcal conjugate vaccine (PCV13) and then is followed at least two months later by the 23-valent pneumococcal polysaccharide vaccine (PPSV23). Although ideally initiated before chemotherapy, vaccination may also be administered during treatment. Seasonal inactivated influenza vaccination is recommended each autumn, preferably at least two weeks before anticipated epidemic peaks, for all immunocompromised patients.⁵

A 2018 Cochrane review of influenza vaccines in immunosuppressed adults with cancer identified one relevant randomized clinical trial and two cohort studies that assessed all-cause mortality as the primary outcome.⁹ The reviewers reported that the cohort studies showed influenza vaccination was associated with significantly lower mortality, but the randomized controlled trial did not.⁹ A 2023 Cochrane review of vaccines for preventing infections in adults with solid tumors funneled down to 10 relevant studies, five randomized controlled trials and five nonrandomized studies of interventions. They concluded that in adults with solid tumors, herpes zoster vaccines reduce the incidence of herpes zoster and that COVID-19 vaccines probably decrease the incidence of COVID-19 without prior infection. They described the evidence of the effects of the influenza vaccine on all-cause mortality and side effects of any grade as being of very low certainty; the incidence of influenza was not measured.¹⁰

Evolution of recommendations

Over the past decade, recommendations for immunization in adults with cancer have evolved significantly, reflecting advances in vaccine development and a deeper understanding of immunologic responses during and after cancer therapy. In a 2015 review of immunizations in adult patients with cancer, the authors emphasized the importance of administering inactivated vaccines at least two weeks before chemotherapy and avoiding live vaccines during immunosuppression, with limited strategies available to enhance vaccine responses.³ Current recommendations from Hibberd et al published in UpToDate retain those core principles but are more nuanced, incorporating guidance for patients being treated with chimeric antigen receptor T-cell (CAR-T) therapies and B-cell-depleting agents. Substantial changes include the replacement of the PCV13 with expanded-valency formulations such as PCV15, PCV20 or PCV21, either alone or in sequence with PPSV23, offering broader serotype coverage.¹

Similarly, herpes zoster prevention has shifted from reliance on the live attenuated vaccine, which was contraindicated in immunocompromised patients, to universal use of the recombinant zoster vaccine (RZV), which is now preferred due to superior efficacy and safety. Influenza vaccination remains an annual priority, though timing strategies have been refined to optimize immune responses during chemotherapy cycles, and vaccination of household contacts is emphasized. Human papillomavirus (HPV) vaccine eligibility has expanded beyond age 26 years to include selected adults up to 45 years, while recommendations for hepatitis B now call for routine vaccination of all unvaccinated patients with cancer aged 19 to 59 years and for older adults with risk factors.¹

In addition, newer vaccines have entered the landscape: COVID-19 vaccination is now standard for all patients after treatment, and respiratory syncytial virus (RSV) vaccines are recommended for adults aged 50 years and older, including those with cancer. Haemophilus influenzae type b (Hib) vaccination is no longer broadly recommended but reserved for patients post splenectomy or hematopoietic cell transplant.¹

Collectively, these changes highlight a shift from general infection-prevention strategies to more precise, evidence-based recommendations that integrate novel vaccines, broader coverage and therapy-specific considerations to better protect oncology populations.

The consequences of the COVID-19 pandemic

The COVID-19 pandemic significantly disrupted routine adult immunization practices in patients with cancer, largely due to competing healthcare priorities and public health restrictions. As healthcare systems shifted focus to controlling COVID-19, preventive services such as vaccination were given lower priority. Curfews, transportation restrictions and fears of infection further discouraged patients from visiting hospitals, leading to delays or omissions in routine vaccinations.

A cross-sectional study by Ozdemir et al conducted in Turkey between March and November 2020 evaluated pneumococcal vaccination rates in patients with cancer who had received pharmacist counseling.¹¹ Despite these interventions, 102 of 162 (63%) of patients remained unvaccinated after 3 months. The most frequently cited barriers included inability to access healthcare facilities due to pandemic restrictions (34%), lack of vaccine availability (21%) and doubts regarding vaccine necessity (18%). Other reasons included difficulties communicating with specialists, initiation of new chemotherapy regimens, indecision or fear of side effects. Importantly, pharmacist-led counseling persuaded 37% of patients to overcome these barriers and proceed with vaccination, underscoring the role of healthcare professionals in mitigating pandemic-related disruptions.¹¹

In a systematic review and meta-analysis by Ahmed et al published in December 2024, the authors highlight the profound impact of the COVID-19 pandemic on immunization and overall outcomes in patients with cancer.¹² The review synthesized findings from 27 studies conducted between 2020 and 2023 that covered multiple cancer types, including gastric adenocarcinoma, breast, lung, gynecologic, colorectal and hematologic cancers. Across studies, mortality rates among COVID-19- infected patients with cancer were consistently higher compared with their noninfected counterparts, with a pooled analysis showing a 19.1% rate among infected patients versus approximately 1% in those not infected with COVID-19.¹²

Beyond mortality, the pandemic disrupted routine cancer care and immunization schedules. Many patients experienced delays in diagnostic workups, cancellations of follow-up visits, interruptions of systemic therapy and reduced access to surgical interventions. Screening program suspensions were associated with later-stage presentations and more invasive surgeries, particularly in breast and gastric cancer populations. Psychosocial impacts, including heightened distress in patients with lung cancer and care disruptions among adolescents and young adults, were also noted. Furthermore, patients receiving active cancer treatment within 14 days of COVID-19 infection were at elevated risk of severe complications, such as acute respiratory distress syndrome, septic shock and myocardial infarction.¹²

The pandemic also reshaped vaccine outcomes in oncology. Clinical trial data demonstrated robust efficacy of COVID-19 vaccines in patients with cancer, although side effects were more experienced by cancer patients than by those without cancer. Nevertheless, vaccination remained a cornerstone in reducing morbidity and mortality, underscoring the need for timely immunization strategies tailored to immunocompromised groups.¹²

Overall, the evidence underscores that COVID-19 not only increased direct health risks for patients with cancer but also indirectly worsened outcomes through disruptions in immunization and cancer care delivery. These findings emphasize the importance of safeguarding immunization programs, maintaining continuity of oncologic care and implementing infection-control strategies to protect this highly vulnerable population during pandemics.¹²

Immunogenicity, effectiveness and safety in cancer populations

IMMUNOGENICITY

Immunogenicity of vaccines in adults with cancer is highly variable and depends on the type of malignancy, intensity of therapy and timing of administration relative to immunosuppression. Patients with hematologic malignancies generally demonstrate weaker immune responses than do those with solid tumors, but both populations face impaired protection during chemotherapy. Live-virus vaccines are contraindicated during immunosuppression due to the risk of disseminated infection, while nonlive vaccines administered during chemotherapy often produce attenuated or unreliable immune responses. ASCO guidelines for adults with cancer say that vaccination should ideally occur by two to four weeks before any planned cancer treatments.² Some experts distinguish between the timing of nonlive and live vaccines, recommending that live vaccines be given four or more weeks before chemotherapy while countenancing vaccination with nonlive vaccines two or more weeks in advance of chemotherapy.¹ If nonlive vaccines are administered during chemotherapy, these doses are typically considered ineffective unless protective antibody titers can be confirmed, and revaccination after immune reconstitution is usually required.¹

Specific studies highlight the diminished but still clinically relevant immunogenicity of certain vaccines. Influenza vaccination is recommended annually, with the best immune responses observed when administered before chemotherapy or early in a treatment cycle; however, responses remain suboptimal and protection is incomplete. Limited data suggest that antibody titers against tetanus, diphtheria and pertussis (Tdap) may wane significantly during intensive treatment, underscoring the importance of booster administration posttreatment. For hepatitis B, patients with cancer often have low seroconversion rates; while high-dose or extended regimens may improve outcomes, responses remain inferior compared with those of immunocompetent individuals. HPV and meningococcal vaccines also elicit suboptimal immune responses, necessitating careful consideration of timing and patient-specific factors.¹

Emerging evidence supports the immunogenicity of newer vaccines in immunocompromised patients. For example, RZV has demonstrated robust humoral and cell-mediated responses in patients with both solid and hematologic malignancies, though responses are stronger when given prior to chemotherapy. In a trial of patients with hematologic cancers, over 80% mounted a humoral immune response compared with less than 1% in the placebo group, with persistence for over a year. Likewise, RSV vaccination has shown immunogenicity in observational cohorts of immunocompromised individuals, including those with cancer, with protective efficacy against hospitalization.¹

A study of patients treated with allogeneic hematopoietic stem cell transplant (HSCT) and RSV administration found that seroconversion occurred in 75% patients beyond one year following the transplant, with seroconversion defined as a fourfold increase in antibodies.¹³

In sum, vaccine-induced immunity in patients with cancer is frequently impaired, but strategic timing and use of nonlive formulations can optimize immunogenicity and provide meaningful protection against preventable infections.¹

CLINICAL EFFECTIVENESS

The ASCO guidelines on vaccination of adults with cancer emphasize that vaccine efficacy in this population is influenced by cancer type, treatment modality and timing of administration. Evidence shows that COVID-19 vaccines induce protective responses, though seroconversion is reduced compared with healthy adults. Rates remain high in patients with solid tumors but are markedly lower in those with hematologic malignancies, particularly chronic lymphocytic leukemia, and are further impaired by B-cell-depleting therapies, CAR-T therapy and other targeted agents. Despite these attenuated immune responses, vaccination significantly decreases hospitalization and mortality risk, with one large study reporting more than a 50% reduction in odds of severe outcomes among vaccinated patients.²

Influenza vaccines also demonstrate protective efficacy, with randomized trials indicating that high-dose formulations improve seroconversion compared with standard-dose vaccines and that vaccination remains effective when administered during chemotherapy, with some evidence supporting administration at the beginning of treatment cycles. Chemotherapy can result in lower antibody titers from hepatitis B vaccination, and the ASCO guidelines recommend use of higher-antigen formulations. Monitoring of postvaccination antibody levels is recommended. HPV vaccination is immunogenic in young cancer survivors, who face an increased risk of secondary HPV-related cancers, underscoring its preventive value.²

Pneumococcal vaccination reduces pneumonia and hospitalization in cancer patients, with conjugate vaccines producing stronger responses than polysaccharide formulations, particularly when given before the onset of treatment or hypogammaglobulinemia. RZV is immunogenic in both solid tumor and hematologic malignancy populations, with optimal responses observed when administered before immunosuppressive therapy, and pivotal transplant trials have demonstrated robust protection against herpes zoster. In recipients of hematopoietic stem cell transplants and CAR-T therapy, vaccines are immunogenic but yield weaker and less durable responses. As a result, revaccination strategies and the use of high-dose influenza vaccines and conjugate pneumococcal vaccines are important.²

Overall, the evidence consistently supports vaccination in patients with cancer as an effective means of reducing infection risk, hospitalizations and mortality, provided that timing and formulation are carefully considered, despite a tendency for blunted immunological response to vaccines in patients with cancer.²

SAFETY CONSIDERATIONS

Nonlive vaccines are broadly considered safe for patients with cancer, although their efficacy may be reduced during periods of active chemotherapy or immunosuppression. The COVID-19 vaccine is recommended after completion of treatment. Annual administration of the nonlive influenza vaccine is strongly recommended, even during chemotherapy, though the immune response may be diminished. Intranasal live attenuated influenza vaccines are contraindicated, but nonlive formulations are safe for family members and healthcare workers, with particular precautions in households of HSCT recipients.¹ Pneumococcal vaccines (PCV15, PCV20, PCV21, PPSV23) are safe and reduce morbidity, with conjugate formulations preferred. Tdap vaccines can be safely administered, with boosters timed around chemotherapy cycles for optimal immune response. Hepatitis A and B vaccines are safe, though efficacy may be reduced; higher dosing strategies have been explored but are not routinely recommended. HPV vaccines are safe but may yield lower antibody titers in patients with cancer; they require caution in thrombocytopenic individuals. Meningococcal vaccination is safe and recommended in patients with cancer with standard indications, though responses may be suboptimal. Hib vaccination is generally unnecessary in adult patients with cancer unless they are posttransplant or postsplenectomy, while the inactivated polio vaccine is safe but may be less effective in immunocompromised individuals. Finally, the RSV vaccine has been shown in observational studies to be safe and immunogenic in immunocompromised adults, including those with malignancy; it is best administered during immune recovery to maximize protection.¹

The nonlive RZV is the preferred formulation for preventing herpes zoster in patients with cancer, given its superior efficacy and safety compared with the discontinued live attenuated zoster vaccine. RZV is recommended by the ACIP for immunocompromised individuals at least 19 years old, including those with cancer. It is administered in two doses spaced two to six months apart, although the interval can be shortened to four weeks in patients expected to undergo immunosuppression. Clinical trials have demonstrated that RZV is safe and immunogenic in both solid tumor and hematologic cancer populations, with durable humoral and cell-mediated immune responses persisting beyond one year. Importantly, patients vaccinated prior to chemotherapy initiation mount stronger immune responses compared with those vaccinated during chemotherapy, though responses are still clinically meaningful in both groups. The side effect profiles are comparable to those seen with placebo, and vaccination significantly reduces the risk of herpes zoster incidence and hospitalization in oncology patients.¹

In contrast, the live vaccine, while shown to provide some degree of protection, is contraindicated in immunocompromised patients due to the risk of vaccine-derived disseminated infection, with rare fatal cases reported in individuals with a history of chemotherapy or targeted immunosuppressive regimens. In settings where RZV is unavailable, prior vaccination with the live attenuated vaccine may confer partial protection, but revaccination with RZV after chemotherapy remains the preferred strategy.¹

With respect to other live-virus vaccines, safety considerations in oncology patients are critical. Live attenuated formulations (including those for measles, mumps, rubella [MMR] and varicella) are contraindicated during active chemotherapy or periods of severe immunosuppression. Immunization with these vaccines should occur prior to the initiation of immunosuppressive therapy when feasible. For patients lacking immunity to MMR, vaccination before therapy is recommended, as patients with cancer who contract measles face a high mortality risk. Severely immunocompromised individuals exposed to measles should instead receive intravenous immune globulin for postexposure prophylaxis. Similarly, seronegative adults with cancer are at increased risk of severe primary varicella infection, making varicella vaccination important when administered before chemotherapy. Transmission of vaccine virus from vaccinated household contacts is rare, though contact avoidance is recommended if a postvaccination rash develops. Evidence from pediatric oncology demonstrates that varicella vaccination after completion of leukemia therapy is both safe and effective, supporting a strategy of posttreatment immunization in selected adult patients with cancer as well.¹

Overall, the use of nonlive vaccines has established a favorable safety profile in immunocompromised patients with cancer, whereas live-virus vaccines must be carefully timed to minimize risk and maximize protection.¹

Integration into the cancer journey

Integration of immunization into cancer care has become a central component of supportive oncology practice, reflecting both the elevated infection risk in immunocompromised patients and the expanding availability of safe, effective vaccines. The 2024 ASCO guidelines stress that vaccination should be viewed as a key element of comprehensive cancer management, beginning with documentation of vaccine history at the first oncology visit and coordination with primary care providers, pharmacists and nursing staff to ensure adherence to recommended schedules. Ideally, patients should receive routine seasonal and age-based vaccines — such as influenza, COVID-19, pneumococcal, recombinant zoster and hepatitis B — at least two to four weeks before initiating cancer therapy to optimize immune responses, though nonlive vaccines can still be administered during or after treatment if necessary.²

Special attention is required for patients undergoing HSCT, CAR-T therapy or B-cell-depleting therapy, as these groups often lose preexisting immunity and require full revaccination beginning six to 12 months posttreatment, with modified timelines for certain agents, such as COVID-19 and influenza vaccines. Live vaccines remain contraindicated in most cancer patients because of the risk of uncontrolled infection. In contrast, nonlive vaccines — including messenger RNA, recombinant and conjugate formulations — are generally safe, though immunogenicity may be attenuated by active disease or treatment with cytotoxic chemotherapy, targeted therapies or immunosuppressive agents.²

Beyond direct patient care, integration extends to vaccinating close contacts and household members, thereby reducing secondary exposure risks. Survivors and long-term patients are also targeted for revaccination strategies to maintain durable protection. ASCO further notes that immunization in oncology requires collaboration across specialties and alignment with ACIP schedules, with modifications for specific cancers when necessary. Collectively, these recommendations underscore that vaccination is no longer ancillary but integral to cancer care, ensuring both infection prevention and improved overall treatment outcomes.²

Evidence gaps and future directions

The ASCO guidelines highlight multiple evidence gaps and areas where further research is needed in the vaccination of adults with cancer. Across most vaccines, the available data are limited by small numbers of randomized controlled trials and reliance on nonrandomized studies and heterogeneous study populations. For COVID-19 vaccines, the guidelines note uncertainty regarding the optimal timing of vaccination following CAR-T therapy and B-cell-depleting therapies, as well as limited understanding of the durability of vaccine responses in hematologic malignancies. Similarly, while influenza vaccines have been studied in oncology settings, questions remain about the most effective timing during chemotherapy cycles and the comparative benefits of high-dose, adjuvanted or two-dose regimens in adults with cancer.²

For several vaccines (e.g., hepatitis B, HPV, RSV and Tdap), the literature review done to prepare the ASCO guidelines identified no eligible studies. This absence underscores a need for focused trials to evaluate immunogenicity, clinical protection and optimal dosing schedules in oncology patients. Additional gaps include limited data on pneumococcal conjugate vaccine use in hematologic cancers and after HSCT, uncertainty regarding the long-term protection of RZV and the absence of studies addressing RSV vaccination in patients under 60 years old who have cancer.²

In the HSCT setting, unresolved questions include whether immune marker-guided vaccination strategies (using CD19/CD27 counts, immunoglobulin G levels or CD4 counts) improve outcomes compared to standard time-based schedules and the durability of protection following posttransplant vaccination. Further, the potential need for booster doses and the role of newer vaccines, such as PCV20 and the HPV 9-valent formulation, require study in transplant and cellular therapy recipients.²

Overall, the guidelines send the message that although vaccines remain a critical component of supportive oncology care, substantial evidence gaps persist in defining optimal timing, dosing and long-term efficacy in immunocompromised cancer populations. Future prospective, controlled studies are needed to refine vaccine strategies and enhance protection for this high-risk group.²

Conclusion

Vaccination is a cornerstone of infection prevention in oncology, yet its application remains inconsistent and underutilized despite clear evidence of benefit. Patients with cancer are uniquely vulnerable to vaccine-preventable diseases due to both disease-related and treatment-induced immunosuppression, and while immune responses may be attenuated, strategic use of nonlive vaccines provides meaningful protection that translates into reduced morbidity, mortality and healthcare utilization. Recent advances — including expanded-valency pneumococcal vaccines, RZV and COVID-19 and RSV immunizations — have broadened preventive options, while evolving guidelines from ASCO, ACIP and international authorities increasingly reflect therapy-specific considerations and survivorship needs. At the same time, the COVID-19 pandemic underscored how disruptions in routine immunization can exacerbate risks in this population, highlighting the critical importance of continuity of preventive care. Persistent evidence gaps — such as optimal timing, dosing strategies and long-term durability of protection in specific oncology subgroups — demand ongoing investigation.

Moving forward, integration of vaccination into the cancer care continuum, supported by multidisciplinary coordination and proactive counseling, should be prioritized as an essential element of supportive oncology. By embedding immunization into standard practice, oncology teams can mitigate infection-related complications, safeguard treatment outcomes and enhance quality of life for patients across the cancer journey. •

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