Shielding the Vulnerable: A Multicentre Australian Rollout of Evusheld to Patients with Chronic Lymphocytic Leukaemia (CLL-SHIELD)

Abstract

Background Patients with CLL are vulnerable to COVID-19 infection and complications due to underlying immunosuppression and B-cell depleting/targeted therapy (Chatzikonstantinou, Leukemia 2021). Furthermore, CLL patients have reduced seroconversion to all available COVID-19 vaccines, despite multiple dosing (Langerbeins, Blood 2022). Tixagevimab and Cilgavimab (Evusheld) was approved for pre-exposure COVID-19 prophylaxis based on the global PROVENT study in patients at risk of inadequate vaccine response, including 383 (7.4%) with cancer, but with no specific CLL data reported (Levin NEJM 2022). Patients with CLL may derive particular benefit from passive immunization, but also may be uniquely exposed to side-effects including compound cardiac signals for both Evusheld and BTKi, and injection site bleeding from BTKi anti-platelet effects. On 17 June 2022, Evusheld became publicly available to all CLL patients in Victoria, regardless of treatment status. Herein we describe the rapid rollout of Evusheld at 2 major Melbourne centers, including the establishment of a CLL cohort (CLL-SHIELD) for prospective follow-up of toxicity and efficacy. Methods: Evusheld was offered to all patients with CLL at the Peter MacCallum Cancer Center (PMCC) and Alfred Health (AH) from 20 June 2022. The rollout occurred via email or direct clinician contact (phone or in-person) at PMCC, and via hard copy mail, e-mail or direct contact at AH. Patients consenting to Evusheld were offered enrollment onto CLL-SHIELD, with planned review of patient-reported adverse events and incidence of interim COVID-19 infections via a standard questionnaire at 3, 6, and 12 months post administration. Data are de-identified at site and aggregated for analysis, with planned sensitivity analyses for treatment-center effect. Both centers have adapted a general policy of withholding any BTKi therapy for 5 days prior to and 2 days post administration to mitigate potential injection-site bleeding risk. Results: A total of 475 patients with CLL were contacted from PMCC (n=367) and AH (n=108) in the first 5 weeks of rollout. Patient-clinician discussion took place directly in person or by phone for 251 (53%) of patients, whereas 183 were contacted only by e-mail, and 41 by hard copy mail. The proportions of patients consenting to Evusheld by initial contact methods were 77.6% (n=195) for direct contact, 29.5% (n=54) for e-mail, and 12.2% (n=5) for hard copy mail (p<0.00001). Twenty-six patients who did not respond to e-mail/mail were contacted directly by their clinicians for in-person discussions; all 26 subsequently consented to Evusheld. In total, the proportion of patients who declined Evusheld following in-person consultation was 8.3% (n=23), with a further 9.7% (n=27) currently remaining undecided. The rate of Evusheld decline for patients contacted by e-mail or mail cannot be determined as only one patient replied with a clear negative response. At data cut-off, 182 of 280 (65%) consenting patients have received or have a booking to receive Evusheld. Rollout of Evusheld is ongoing at both centers and all consenting patients will be offered enrolment onto CLL-SHIELD for prospective monitoring of efficacy and toxicity. Clinical results from the 3-month post Evusheld data-cut, including rates of adverse events and COVID-19 infection, will be presented at the meeting. Conclusion: Rapid implementation of an Evusheld program is feasible in a large CLL population. Patient uptake of Evusheld was significantly higher following direct patient-clinician contact, likely due to improved opportunities for informed discussions, although this approach places short-term strain on healthcare resources. Evusheld has high acceptance rate among CLL patients, with <10% declining pre-exposure prophylaxis following in-person consultation.