Introduction: In patients with multiple myeloma (MM), SARS-CoV-2 infection has been associated with severe clinical course and high mortality rates, due to the concomitant disease- and treatment-related immunosuppression. Furthermore, immune response to COVID-19 vaccination is attenuated. Therefore, patients with MM are eligible to receive pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld).
Methods: Consecutive patients with MM were prospectively enrolled in the study. All patients were at high risk for severe COVID-19 due to the underlying MM. All patients had negative polymerase chain reaction (PCR) test for SARS-CoV-2 before the administration of monoclonal antibodies for COVID-19 prophylaxis. All patients had measurement of neutralizing antibodies (NAbs) against SARS-CoV-2 using an FDA approved methodology (enzyme-linked immunosorbent assay, cPass SARS-CoV-2 NAbs Detection Kit; GenScript, Piscataway, NJ, USA) before the administration of tixagevimab/cilgavimab and at one month thereafter. Baseline demographic and clinical characteristics, NAbs levels and patient outcomes were collected and analyzed. Evusheld was administered at 150mg as two intramuscular injections.
Results: Fifty-five patients with MM were included in this analysis and were followed for a median of 5 months (range 3-6 months) after receiving tixagevimab/cilgavimab. The median age was 63 years (range 36-84), whereas 27 (49%) were females. The majority of the patients had performance status (PS) 0 (n=27, 49%), 22 patients (40%) has PS 1 and 6 patients (11%) had PS 2. Thirty patients (55%) were ISS 1, 17 (30%) were ISS 2 and 8 (15%) were ISS 3. Most patients (n=37, 67%) were at their first line of treatment, 16 (19%) were receiving their second line of treatment, one patient was at the third and one at the fifth line of treatment. Thirty-one patients (56%) had previously received autologous stem cell transplant. At the time of tixagevimab/cilgavimab administration, 19 patients (34%) were receiving combinations including anti-BCMA agents, 24 patients (44%) were receiving combination including anti-CD38 drugs and 12 (22%) were on other treatments. Four patients had a prior history of COVID-19. Regarding vaccination status for COVID-19, 42 patients (76%) had received 4 vaccine doses and 13 patients (24%) had received 3 vaccine shots. All patients were vaccinated with mRNA-based vaccines.
The median NAb level before the administration of tixagevimab/cilgavimab was 87% (range 0-98%), whereas it increased to 97% (range 0-98%) at one month thereafter. Overall, 5 patients (9%) were diagnosed with COVID-19 at a median of 1 month (range 1-2) after receiving tixagevimab/cilgavimab. All of these patients received nirmatrelvir/ritonavir (Paxlovid) for 5 days as outpatients along with supportive care as per standard clinical practice and recovered completely. There were no COVID-19-related hospitalization or deaths. Tixagevimab/cilgavimab was well tolerated; no infusion-related reactions or major adverse events were reported. Fifteen patients (27%) experienced pain at the injection site that resolved after a few days.
Conclusions: Tixagevimab/cilgavimab (Evusheld) seems beneficial in patients with MM who had a low incidence of COVID-19 infections during the Omicron wave. No new safety concerns emerged. An anamnestic dose is scheduled at 6 months after the prime dose.