ABSTRACT
Background: Adults and childrenwith cancer are susceptible to severe SARS-CoV-2 disease. Vaccination is protective;data beyond initial response and regarding effect of booster doses are lacking in cancer patients. Method(s): The SerOzNET study assesses SARS-CoV-2 vaccine response in haematological and solid cancer patients aged 5 and older. Patients are recruited pre dose 1 and receive standard BNT162b2 (Pfizer) or ChadOx1-S (AstraZeneca) vaccine. Blood is taken at baseline and after each dose. Neutralizing antibody (NAb) titre, absolute antibody titre (Abbott), T cell response (IFN-gamma) and epigenetics are analysed. Clinical data are collected. Patients are followed for up to 3 months beyond dose 5. Result(s): 105 children (64% haem, 36% solid cancers) and 399 adults (35% haem, 65% solid cancers) were enrolled. In adults, NAb response rate increased after dose 3 (Post 2: 40% haem, 87%solid;Post 3:70%haem,97%solid). Post dose 2, predictors of nonresponse were ChadOx1-S vaccine (OR 3 p = .02), haem cancer (OR 14 p < .001), ECOG >=1 (OR 2.6 p = .01) and steroids (OR 5 p = .01). Post dose 3, only haem cancer predicted non-response (OR 16). IFN-gamma response is available for a subset, detectable in 41/90 (46%) postdose 1, 78/96 (81%) post-dose 2 and 35/42 (83%) post-dose 3;without significant difference between haem and solid cancer. In children, NAb response post dose 2 is available for 50 patients. Response rate between haem (19/31, 61%) and solid patients (13/19, 68%) was similar. IFN-gamma response post dose 2 was also similar: (14/22, 63%) vs solid patients (12/14, 85%) (p = .25). Analysis is ongoing. Conclusion(s): Response to two doses of SARS-CoV-2 vaccine is suboptimal in patients with cancer. The third priming dose is integral, with significantly higher response rates observed. 36% of children did not develop neutralizing antibodies post dose 2;subsequent doses are likely to be important for young patients.
ABSTRACT
Background: COVID-19 disease is more severe in unvaccinated cancer patients compared with the general population. There is limited data regarding clinical efficacy of vaccination in these patients. Method(s): SerOzNET (ACTRN12621001004853) is a prospective observational cohort study of adults and children with cancer receiving COVID-19 vaccination. The primary endpoint is serological response. An important secondary endpoint is outcome of COVID-19 infection after vaccination. We report self- and clinician reported COVID-19 infections. Result(s): Of 395 adults (20 years +), 74 (19%) reported COVID-19 infection over mean duration on study of 259 days. 71 (97%) had received 2 vaccine doses, 51 (69%) received 3+ doses. 21 (28%) had antiviral treatment. 62 (84%) had symptoms, 7 (9%) required hospitalisation, 0 required ICU admission or died due to COVID-19. Of 113 children/adolescents (5-19 years), 31 (27%) reported COVID-19 infection over mean duration on study of 215 days. 28 (90%) had received 2 vaccination doses, and 12 (39%) received 3+ doses. 23 (74%) had symptoms, 8 (25%) required hospitalisation, 2 (6%) had antiviral therapy, 0 required ICU admission or died due to COVID-19. Pediatric pts with COVID-19 infection had increased risk of hospitalisation compared with adults (p=0.03). Hematological cancer pts had non-significant but numerically higher rates of hospitalisation (Table). [Formula presented] Conclusion(s): Pts with cancer are likely to be exposed to COVID-19, with infection rates similar to the wider population. Vaccination appears to protect against ICU admission in cancer patients. However, 9% of adults and 25% of children with cancer required hospitalisation for COVID-19, demonstrating increased severity of symptoms compared to the general population. Higher rates of infection and hospitalisation in pediatric pts may be partly attributable to the lower proportion of children who had received a 3rd vaccination dose at the time of infection. Clinical trial identification: ACTRN12621001004853. Legal entity responsible for the study: Monash Health. Funding(s): Cancer Australia (Australian Federal Government) Victorian Cancer Agency (Victorian State Government, Australia) Leukaemia Foundation (Foundation, Australia). Disclosure: All authors have declared no conflicts of interest. Copyright © 2022
ABSTRACT
Background: There is limited published data regarding safety and toxicity of Sars-CoV-2 vaccination in patients with cancer. This may contribute to vaccine hesitancy amongst some members of this vulnerable cohort (Nguyen 2022). Methods: SerOzNET (ACTRN12621001004853) is a large prospective cohort study of adults and children with cancer undergoing Sars-CoV-2 vaccination. Participants undertake surveys by text message link sent to their mobile phone, or on an iPad provided in clinic. A validated hesitancy survey is undertaken at enrolment (Oxford COVID-19 Vaccine Confidence and Complacency Scale), and prior to the 3rd vaccine dose. For children, a parental survey is also collected. Quality of life is assessed with serial EORTC QLQ-C30 (adults) or PedsQL (children, self- and parentreport) at baseline and serially throughout the study. Patient- reported vaccine toxicity is assessed by patient-reported CTCAE items for common vaccine related AEs and patient-reported impact of vaccination on cancer treatment (delays, hospitalisations). Medically ascertained vaccine toxicity is assessed by study investigators one month after the 3rd vaccination dose. Results: Five hundred and four participants have been enrolled (403 adults (80%) and 101 children (20%)). Hesitancy: At baseline, 351 adults (88%) and 56 children (55%) responded. The adult cohort was predominantly female (67.2%) with an average age of 53.8 years. Preliminary analysis showed similar levels of vaccination concerns between baseline (mean score = 18.4, SD = 5.1) and follow-up pre-3rd dose (mean score = 17.9, SD = 5.7) in adults. We will present results regarding whether self-reported COVID-19 vaccine toxicity after the first dose was related to change in hesitancy scores at follow-up, which may have implications for COVID-19 vaccine booster willingness. Patient toxicity surveys have been returned post dose 1 for 445/497 (91%), post dose 2 for 417/457 (91%) and post dose 3 for 280/334 (84%). Incidence of any AEs was high (77-100% depending on age and dose), however the incidence of severe AEs (patient reported) was low (0-10% depending on age and dose). Interruptions to cancer treatment after vaccination were uncommon (2-12%). Pain at the injection site was the most commonly reported AE for all ages and doses. Hospital admissions (any reason) were reported post dose 1 in 4/15 children aged 5-12, but were uncommon in older adolescents and adults. The most common systemic adverse effect was rigors in children 5-12, while adolescents and adults reported fatigue most frequently. Quality of life analysis is ongoing and will be presented at the meeting. Conclusions: It is feasible to collect detailed toxicity and quality of life data in a large cohort of cancer patients receiving COVID-19 vaccinations. Data to date are reassuring that severe adverse events and interruptions to cancer therapy are uncommon.
ABSTRACT
Background: COVID-19 infection has poor outcomes for patients (pts) with cancer. Understanding vaccine response as a correlate of protection from severe infection is essential to advise pts regarding protective behaviours and optimal vaccine schedule. This Australian cohort is unique due to low rates of COVID-19 exposure at study entry (July-November 2021). and use of a 3 dose schedule. Pts initially received 2 doses of either BNT162b2 (Pf) at a 3 week interval, or ChadOx1-S (AZ) at a 6 week interval, all then received a 3rd dose, either mRNA-1273 (Mod) or Pf after 2-4 months, and finally a 4th dose at an interval of a further 3 months, for a subset. Methods: SerOzNET (ACTRN12621001004853) has enrolled pts with solid and haematological (haem) cancers prior to initial vaccination. Serial blood samples were processed for serum, PBMC and PMN at timepoints: 0, then 3-4 weeks post dose 1 then 2 then 3 then 4 (where administered). We report here neutralizing antibodies (nAb) against wild type (wt) and delta and omicron variants of concern (VOC);quantitative S-protein IgG antibody (Abbott);Tcell correlates measured by levels of interferon-g (IFN g), tumour necrosis factor-a, interleukins (IL-) 2/ 4/5/13;and epigenetic profiling of T cells. Results: The cohort consists of 401 pts with median age 58 (range 18-85);59% female;128 (32%) haem cancers. 377 (94%) are on current or recent (< 12 months) systemic therapy: 162 (43%) chemotherapy, 62 (16%) immunotherapy, 40 (10%) combined chemo/immunotherapy, 113 (29%) hormonal or targeted therapy. 42 (10%) received anti-CD20 therapy < 12 months, 6 (1.4%) had allogeneic stem cell transplant. NAb levels against wt are available for 256 pts post dose 1, 245 pts post dose 2 and 159 pts post dose 3 (will be updated). Response rates post dose were respectively 27%, 77% and 88%. Pts with haem cancer were less likely to respond to vaccination at any time compared to pts with solid cancer (p < 0.001, chi-squared test). After 3 doses, 3.8% of pts with solid cancer and 27.8% with haem cancer lacked NAb. NAb results to VOC delta are available for 92 pts post dose 2: 25/92 (27%) were negative, compared with a non-response rate to wt of 15% at same time in same pts. IFN-γ-Spike response was detectable in 18/31 (58%) and 24/30 (80%) pts post dose 1 and 2 respectively. 101 pts to date have received a 4th dose;data will be available at the meeting, as will epigenetic profiles and detailed clinicopathological correlations. Conclusions: This interim analysis shows that a significant proportion of pts with haem cancers (27.8%) lack protective Sars-CoV-2 antibodies following 3 vaccinations, whereas only 3.8% of solid cancer pts lack detectable response. Results from other B and T cell parameters may also be important in identifying pts less well protected by vaccination. Follow up is ongoing, response rate post 4th dose will be presented at the meeting.
ABSTRACT
Background: Defining cancer and treatment-related factors which influence protection against COVID-19 following vaccination are important given the worse outcomes following infection in this group. Sophisticated and detailed studies which go beyond a single measure are required particularly with correlation to multiple disease and treatment factors. This study cohort is unique due to (a) very low prior COVID-19 infection at time of sampling (July-Nov 2021), (b) vaccines studied were BNT162b2 (Pf) given 3 weeks apart or ChAdOx1 (AZ) spaced 12 weeks (dose 1, 2) (c) most participants then received a third dose 2 months later (heterologous for AZ). Methods: SerOzNET (ACTRN12621001004853) enrols Australian blood and solid cancer patients prior to vaccination, with serial blood analyses and qualitative measures. We measured neutralizing antibodies (nAb) against SARS-CoV-2 wild type (wt) and variants of concern delta and omicron, quantitative S-protein IgG antibody level (Abbott), and T-cell correlates (interferon-g, tumour necrosis factor-a, interleukins 2/4/5/13) and epigenetic profiling at baseline and 3-4 weeks post dose 1, 2 +/- 3.Results: 379 participants were included, median age 58 years (IQR 47-66) and 60% female. 30% participants had hematological malignancies with the remainder solid organ cancers. 90% patients were on current systemic cancer treatment (most commonly chemotherapy in 41%, chemoimmunotherapy or immunotherapy in 20%). In 331 patients where treatment intent was recorded, 47% was palliative. Only one patient had known prior COVID-19 infection. Of the initial 94 participants who received Pf vaccination, median (IQR) neutralizing antibody titre 4 weeks following dose 2 was 80 (40-160) for SARS-CoV-2 wt and 40 (0-80) for delta variant. Conclusion: Neutralizing antibody titres in this Australian cancer population following Pf vaccination appear lower than those reported elsewhere such as CAPTURE study (Fendler et al, 2021), possibly related to shorter interdose interval. Preliminary data highlights low nAb titres as expected in haematology patients but also in some cases with treatment not traditionally associated with immunosuppression such as hormonal therapy. These results will be updated in February 2022 with third dose, AZ and omicron variant data.
ABSTRACT
Introduction Limited data exist regarding safety of COVID19 vaccinations for patients with cancer. Methods SerOzNET (ACTRN12621001004853) is a large prospective study of adults and children with cancer undergoing Sars-CoV-2 vaccination. Participants undertake a validated hesitancy survey at enrolment (Oxford COVID-19 Vaccine Confidence and Complacency Scale) and prior to the 3rd vaccine dose. Quality of life is assessed with serial EORTC QLQ-C30 (adults) or PedsQL (children). Patient- reported vaccine toxicity is assessed by patient-reported CTCAE items for common vaccine related AEs and patient-reported impact of vaccination on cancer treatment . Medically ascertained vaccine toxicity is assessed by study investigators one month after the 3rd vaccination dose. Results Five hundred and four participants have been enrolled (403 adults (80%) and 101 children (20%)). Baseline hesitancy surveys have been completed by 349 adults (87%), 58 parents (57%) and 51/86 eligible children (59%). Patient toxicity surveys have been returned post dose 1 for 445 (88%), post dose 2 for 417 (83%) and post dose 3 for 280 (56%). Incidence of any AEs was high (77-100% depending on age and dose), however the incidence of severe AEs (patient reported) was low (0-10% depending on age and dose). Interruptions to cancer treatment after vaccination were uncommon (2-12%). Conclusions Data to date are reassuring that severe adverse events and interruptions to cancer therapy post COVID19 vaccination are uncommon.
ABSTRACT
Background The COVID-19 pandemic has necessitated a restructuring of cancer care due to resourcing demands and revised risk-benefit considerations which relate the risks of cancer progression with the risks of COVID-19 related morbidity and mortality. Specific treatment adjustments for individual patients have not been widely reported. The impact of treatment changes on the outcome of cancer patients have also not been well documented. We report the experience of a large Australian metropolitan multisite cancer service that undertook proactive review of systemic anti-cancer therapy (SACT) of all patients in response to the pandemic. The aim was to re-balance the risks and benefits of current treatment strategies in light of the pandemic. Method From March-April 2020, all current SACT orders (excluding those related to clinical trials) were reviewed by an independent team of clinicians. Patients on curative therapy, or with large perceived benefit were reviewed but not included in further processing. For all other SACT orders, a documented recommendation regarding planned treatment was sent to the patient's individual clinician for consideration. A categorical assessment of the recommendations is presented. Results 570 SACT orders were reviewed, pertaining to 317 patients. 731 individual recommendations were made. The cohort consisted of 130 males and 187 females, with a median age of 62 years. Treatment was undertaken with curative intent in 38% of patients, while 62% of patients were treated with palliative intent. Distribution by tumour types was typical of epidemiology and casemix of a metropolitan oncology service. The most frequent recommendations made by the independent review team were: no change (23%), change in formulation of same drug (9%), shorten duration of treatment (9%), treatment break (8%), re-evaluate benefit of current treatment (8%), treatment cessation (7%), and referral for home-based treatment (6%). Overall, 71% of recommendations of the review team were accepted by the patient's individual clinician. A variation to recommendations suggested by the review team was implemented for 8% of SACT orders. Recommendations which were not implemented were mostly initiated by the patient's individual clinician (70%), while 14% were due to patient choice. Conclusion This is the only dataset known to date of the impact of COVID-19 on adjustments of SACT for cancer patients at the start of the pandemic in Australia, and provides key insights into discrete adjustments made for cancer patients. The majority of patients underwent modifications in their cancer therapy made in the context of competing risks to their health posed by COVID-19.