Antibody responses to SARS‐CoV‐2 vaccination in patients with acute myeloid leukaemia and high risk MDS on active anti‐cancer therapies

Abstract

To the editor, Encouraging seroconversion rates to SARS-CoV-2 vaccination in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients have been reported in large cohort studies [1][2][3][4] ; however, the majority of these patients were not receiving active systemic anti-cancer therapy (SACT) and its impact on vaccine responses remains to be fully elucidated. Mori et al. 5 report seroconversion rates of 94.7 and 100% respectively in Japanese patients with AML and MDS after two doses of mRNA SARS-CoV-2 vaccine, of which 39% received SACT. We report SARS-CoV-2 antibody responses following vaccination in a UK cohort of AML and HR-MDS patients all receiving, or having recently completed SACT, and stratified by prior SARS-CoV-2 infection. Demographics, SACT history and laboratory parameters were collected from the electronic health records of patients following two doses of SARS-CoV-2 vaccine (BNT162b2 or ChAdOx1nCoV-19) between December 2020 and July 2021. Serological testing was performed using Roche Elecsys anti-SARS-CoV-2 enzyme immunoassays. A total of 39 patients (85% AML, 15% HR-MDS, median age 63 ), underwent serological testing after receiving two doses of vaccine (Table 1). All were tested for anti-S antibodies after two doses (median 40 days post-dose) and 59% after the first dose (median 39 days). Thirty-three patients (85%) underwent testing for anti-N antibodies, and seven (21% of those tested) had previous SARS-CoV-2 infection. Eleven patients (28%) received intensive chemotherapy, 51% venetoclax-combination therapy (with azacitidine, low-dose cytarabine or gilteritinib) and 21% non-intensive azacitidine. Seropositivity rates and antibody titres increased with consecutive vaccine doses, from 74% in all patients (75% AML, 67% MDS) to 95% (94% AML, 100% MDS), with a median anti-S titre of 5.90 U/ml (IQR 0.58-56.7) after dose one, rising to 333 U/ml (IQR 86.8-1971) post dose two. Significantly higher titres were detected after dose two in AML patients, but not in MDS, though numbers are small (Figure 1B). We report similar seroconversion rates following two doses as seen by Mori et al. (Figure 1A, Table 1), despite all our patients receiving SACT compared to 39% of their cohort; however, we found no difference in anti-S titres between AML and HR-MDS patients receiving SACT after

Booster effect of a third mRNA‐based COVID‐19 vaccine dose in patients with myeloid malignancies

“…We have reported that patients with myeloid malignancies were more responsive to 2 doses of COVID‐19 vaccines than patients with lymphoid malignancies 10 . A few later studies confirmed our results 22,23 . In this complementary study, we revealed that both the initial and third vaccine immunogenicity in AML patients, with 37% of those patients receiving active treatment, were comparable to those in HCs.…”

“… 10 A few later studies confirmed our results. 22 , 23 In this complementary study, we revealed that both the initial and third vaccine immunogenicity in AML patients, with 37% of those patients receiving active treatment, were comparable to those in HCs. In MDS patients, with 75% of those patients receiving active treatment, although the initial vaccine immunogenicity was inferior to the initial vaccine immunogenicity in HCs and AML patients, the third vaccine improved the response to a level not inferior to those in HCs and AML patients.…”

“…On the other hand, several studies have shown that venetoclax‐based treatment reduced the COVID‐19 vaccine response for patients with lymphoid malignancies 6,7,17 . However, the impact of venetoclax‐based treatment on vaccine immunogenicity in patients with myeloid malignancies is still controversial 22,25,26 . Because of the small number of patients in our study, it was difficult to perform any further sub‐analysis of the effect of treatment.…”

“… 6 , 7 , 17 However, the impact of venetoclax‐based treatment on vaccine immunogenicity in patients with myeloid malignancies is still controversial. 22 , 25 , 26 Because of the small number of patients in our study, it was difficult to perform any further sub‐analysis of the effect of treatment. Further studies to confirm therapy‐related factors associated with booster vaccine response are needed.…”

Vaccinations in hematological patients in the era of target therapies: Lesson learnt from SARS-CoV-2

“…Similarly to BTKi, TKI and ruxolitinib, these agents are administered continuously, and may induce immune disruption with increased incidence of invasive fungal and bacterial infections [ 78 ]. Recently a seroconversion rate of about 90% was reported in AML/MDS patients vaccinated for SARS-CoV2 and treated with HMA alone or in combination with venetoclax ( Table 5 ) [ 79 , 80 ]. Different results were reported by our group [ 9 ] and in another experience [ 27 ], where venetoclax plus HMA was accompanied by a seroconversion rate of only 33% versus 88% with HMA alone.…”