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Vaccination against COVID for patients suffering from CLL and WM - Recommandations FILO LLC-MW

SARS-CoV-2 infection have a greater severity in patients suffering from maligna hemopathy in general [1,2], and from chronic lymphoïd leukemia in particular [3]. This severity results in an increased risk of developping acute forms of Covid-19 and higher mortality, including after adjusgin with known general risk factors (age, sex, obesity, ...)[1].
The mortality observed on patients suffering from maligna hemopathy and hospitalized for Covid-19 is nearly 35% in recent published studies [2-4] and is even over 45% with patients over the age of 60 [2]. The risk of acute forms of Covid-19 concerns all patients, weather they are currently recieving treatment or not [2], and whatever the delay from initian diagnisis [1]. For patients suffering from CLL, this increased risk is also observed for patients, notably stade A, who have not yet needed specific treatment [3].
The vaccination against Covid is being deployed on French territory since end of 2020 and for now, only mRNA vaccines Comirnaty (Pfizer/Biontech) and Moderna are available. Other vaccines should be available soon, notably the one developped by AstraZeneca, using a different strategy with a viral vector [5].
These vaccines have shown, in studied cohorts of general population, a great protection towards the developpment of acute forms of Covid-19, but there is still unknown informations on duration of vaccine protection and the ability of vaccine to prevent the transmission of the virus. On the other hand, there is no solid data on the protection yeld by the vaccine on immunocompromised patients. The HAS has recommended at the end of november 2020 a strategy of priorisation of populations to vaccinate, since the vaccine supply capacity were limited [6].
Five phases were determined starting with elderly (EHPAD, USLD) and nursing staff of 50 years old and more, or suffering from comorbidity (1st phase), then over 75 years old subjects followed by over 65 years old subjects (2nd phase). An HAS release published on 18th of december 2020 specified these recommandations, including the possibility to discuss, as soon as the begining of the vaccinal phase and on the base of an appreciation of the benefit-risk balance, the vaccination of sub-populations not previously priorised according to their age, but particuliarly vulnerable like patients suffering from severe immunology deficit or acute hemopathy [7].
The board of guidance of vaccination strategy, directed by A. Fischer, validated the priorisation of patients having recieved a cellular therapy and patients suffering from maligna hemopathy, but there has been to this day no official publication.

Which patients shoud recieve the vaccine in priority ?
All patients suffering from CLL and Waldenström Macroglobulinemia (WM) have an increased risk of developping an acute, possibly lethal form of Covid-19, whereas they have not been treated yet (CLL stade A for exemple), patients recieving ongoing chemotherapy or targeted treatment (the protective role of BTK inhibitors initialy supposed seems to be unconfirmed), or patient distant from their treatment.
From this statement, the vaccine should be offered to EVERY patient without the possibility to identify a sub-population being "even more at risk" than any of the other, and therefore suggesting an order of priorization according to their typology.
It is generally recomanded to vaccinate patients who have already caught Covid-19 after a delay of three months post-infection. Patients who, after this three months delay, show a positive Covid-19 serologye are not to be considered prioritized for the vaccination as long as the supply in vaccine is insufficient for the whole population.

Which vaccine to use ?
For now, the question is irrelevant as the only available are the ones using mRNA technology, Comirnaty and Moderna, and there is no expected difference of efficiency between these two vaccines.
When vaccines using a viral vector (non pathogen for human attenuated virus) as the one developped by AstraZeneca, caution would suggest to keep using, at least at first, mRNA vaccines for non-immunocompetent patients.

Are-there contraindication to vaccine for patients suffering from CLL or WM ?
There is no contraindication to vaccine against Covid (by mRNA vaccines) directly connected to the hemopathy itself or its treatment.
Caution is required, as with the general population, for patients with antecedent of severe allergy.

What interval between the two injections ?
Considering the actual limit of supply with vaccine doses, it has been suggested, on the basis of available data and in order to make the vaccine available as soon as possible for as many people as possible, that it could be considered to increase de time between the two doses to six weeks. This proposal is based on observations made in cohorts that did not include immunodepressed subjects.
Therefore, considering the B and T immune deficiency on patients suffering from maligna hemopathy (especially CLL) and the uncertainty concerning the quality of the vaccine response, it is prefered to respect the usual scheme with an interval of 3 weeks between the two injections (and at least try not to go over 4 weeks).

What timing for the vaccination (patients under treatment) ?
The vaccination can be made at anytime for patients under oral continue therapy. For patients going under chemotherapy, the recommendation existing for other vaccinations suggest to do it if possible between two cures of treatment (although it could imply additional traver if the vaccination is made on site).
Patients included in a prospective clinical trial must, like other patients, have a quick access to vaccine against Covid.

What specific risk of vaccination to anticipate for patients suffering from CLL ?
There is a theoric risk that the inflammatory response to nucleic acid vaccines could be deleterious in subjects with a predisposing field for inflammatory reactions or event autoimmune diseases. This risk is only theoric and the vaccination with a mRNA vaccine (not alive) is not contraindicated in case of auto-immune disease. Due to the propensity of patients with CLL to develop auto-immune manifestations and more particularly autoimmune cytopenias, this theoretical risk must nevertheless be kept in mind and the appropriate investigations should be initiated in case of doubt.

Should the vaccine efficiency be assessed routinely ?
There is to this day no recommandation ∙ for general population ∙ to evaluate the efficiency of the vaccine with serological tests.
The efficiency of vaccination in immunocompromised patients, however, must be evaluated and it can only be recommended to participate in the dedicated cohorts that will be set up.


Références :
1. Williamson EJ, Walker AJ, Bhaskaran K et al. Factors associated with COVID-19-related death using
OpenSAFELY. Nature 2020, 584 : 430-6
2. Vijenthira A, Gong IY, Fox TA et al. Outcomes of patients with hematologic malignancies and
COVID-19: a systematic review and meta-analysis of 3377 patients. Blood 2020, 136: 2881-92
3. Mato AR, Roeker LE, Lamanna N et al. Outcomes of COVID-19 in patients with CLL: a multicenter
international experience. Blood 2020, 136: 1134-43
4. Chari A, Kemal Samur M, Martinez-Lopez J et al. Clinical features associated with COVID-19
outcome in multiple myeloma: first results from the International Myeloma Society data set. Blood
2020, 136: 3033-40
5. Vaccins contre la Covid-19 : questions et réponse. Un texte de la Société de Pathologie Infectieuse
de Langue Française à destination des soignants.
6. Rapport HAS – novembre 2020 : Stratégie de vaccination contre le Sars-Cov-2 Recommandations
préliminaires sur la stratégie de priorisation des populations à vacciner : https://www.hassante.
7. sur-la-priorisation-des-publics-cibles

Rédaction : F. Cymbalista, A. Delmer, P. Feugier, V. Leblond, V. Lévy, A.-S. Michallet | 14 Janvier 2021 |

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