Mixed news from the CLL-VR study into SARS-Cov-2 vaccination in chronic lymphocytic leukemia

[CLLerinOz]

A pre-proof letter in the journal Cancer Cell was released on 6 May, to report on the latest findings of the Birmingham CLL-VR study determining antibody and cellular immune responses after 3rd and 4th SARS-CoV-2 vaccine doses in CLL patients . It contains encouraging news for many CLL patients and not such good news for some.

First the good news:

Around 80% of CLL patients in the study developed an antibody response after 3 vaccine doses and their antibody titres were "comparable with those seen in healthy donors after primary series vaccination. Furthermore, cellular immune responses were also comparable."

There was a marked decrease in hospitalisations with omicron and comparable T cell responses to omicron vs ancestral Wuhan.

( twitter.com/low_helen/statu... )

Now, the not so good news:

"... approximately 20% of patients are refractory to seroconversion and are at increased risk of infection."

"This patient group appear resistant to improvement in humoural immunity and require alternative approaches for immune protection, such as prophylactic monoclonal antibody treatment."

Following the first 2 vaccine doses, the CLL-VR study reported spike-specific antibody responses in 66% (322/486) patients compared to 100% of controls (Parry et al., 2021).

This response rate improved to 80% following the 3rd vaccine dose (298/374) (p<0.0001) but ""the seroconversion rate was not increased further after a 4th vaccine (77%; 132/171) indicating that the proportion of patients who develop a spike-specific antibody response following COVID-19 vaccination plateaus after the 3rd vaccine."

"Regardless of vaccine dose number, a low serum IgM, current BTKi therapy or imminent planned treatment were independent predictors of poor response with an 81% (p=0.003), 90% (p=0.021) and 96% (p=0.027) reduction in probability of response respectively after the 4th dose."

"Monoclonal antibody therapy became available in the community in December 2021 and may have contributed to the reduced rate of hospitalisation, although only 36% of those testing positive during the same period received therapy and indicates a need for caution in predicting individual infection risk on the basis of antibody status in the clinic."

"... neutralization of Omicron was low, although values were broadly equivalent in both CLL participants and controls following a third vaccine dose, whereas cellular responses against Omicron were equivalent to those seen against the ancestral strain amongst vaccinated CLL patients."

"Homologous and heterologous vaccination protocols elicited comparable humoral responses although cellular immunity was stronger following ChAdOx1 primary series. A similar finding has been reported in healthy donors and patients with other hematologic malignancies, and suggests that adenoviral-based vaccines may be particularly effective in generating cellular immunity in patients with immune suppression (Collier et al., 2021; Lim et al., 2022)."

"Blood samples were taken from 404 patients at a median time of 20 days following 3rd dose, of which 161 (40%) had received the BNT162b2 vaccine (Pfizer/BioNTech) as primary series and 243 (60%) had received the ChAdOx1 vaccine (Oxford/AstraZeneca). Almost all patients (393/404) received an mRNA vaccine for 3rd dose (375: BNT162b2; 18: mRNA1273). Samples were also collected from 186 patients following the 4th vaccine dose (Table S1). Patients with clinical or serological evidence of prior natural SARS-CoV-2 infection were excluded from analysis."

doi.org/10.1016/j.ccell.202...

Parry, H., Bruton, R., Roberts, T., McIlroy, G., Damery, S., Sylla, P., Dowell, A.C., Tut, G., Lancaster, T., Bone, D., Willett, B., Logan, N., Scott, S., Hulme, S., Jadir, A., Amin, U., Nicol, S., Stephens, C., Faustini, S., Al-Taei, S., Richter, A., Blakeway, D., Verma, K., Margielewska-Davies, S., Pearce, H., Pratt, G., Zuo, J., Paneesha, S., Moss, P., COVID-19 vaccines elicit strong cellular immunity and robust clinical protection in CLL, Cancer Cell (2022)

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