Humoral serological response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD2O antibodies

Gurion, Ronit; Rozovski, Uri; Itchaki, Gilad; Gafter‐Gvili, Anat; Leibovitch, Chiya; Raanani, Pia; Ben‐Zvi, Haim; Szwarcwort, Moran; Taylor-Abigadol, Mor; Dann, Eldad J.; Horesh, Nurit; Inbar, Tsofia; Tzoran, Inna; Lavi, Noa; Fineman, Riva; Ringelstein-Harlev, Shimrit; Horowitz, Netanel A.

doi:10.3324/haematol.2021.279216

Cited by 54 publications

(76 citation statements)

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“…Overall, these findings may assist haematologists and national health commissions in their decision-making processes regarding preventive measures and treatment in this patient population. Vaccination has been shown to be not as effective in lymphoma patients as in the normal setting, making this population more vulnerable to COVID19 [25][26][27][28] . A substantial subset of vaccinated lymphoma patients may be at high risk of breakthrough COVID19 infection 28 .…”

Section: Discussionmentioning

confidence: 99%

A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study

et al. 2022

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Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behaviour and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not admitted cohort, n=388), or required hospitalization (n=468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95%CI 11-15%) and 23% (95%CI 20-27%), respectively. Anti-lymphoma treatment, including anti-CD20 containing regimens, did not impact on survival. Patients with Hodgkin's lymphoma had the more favourable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment for their underlying disease, and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.

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Section: Discussionmentioning

confidence: 99%

A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study

et al. 2022

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“…We reviewed the literature to gather information on the seroconversion rates after receiving a COVID-19 vaccine in patients with hematologic malignancies. We selected 18 series that provided anti-SARS-CoV-2 spike protein IgG seroconversion rates after full COVID-19 vaccination detailed by hematologic malignancy diagnosis, with at least 20 patients per group (Figure 1 and Supplemental Table 1) (2,(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The literature review also included six additional series that are not included in Figure 1, three due to sampling of serum antibodies before achieving full vaccination as evidenced by lower seroconversions in the healthy control group compared to the rest of the series (20,21), and three that did not provide breakdown of the data according to different histological diagnoses (22,23).…”

Section: Main Textmentioning

confidence: 99%

“…Patients with chronic lymphocytic leukemia (CLL) have a particularly low rate of seroconversion after COVID-19 vaccination, ranging from 39% to 71% in the reported series (2,(5)(6)(7)(8)(9). A similarly low rate of seroconversion is evident in series reporting on patients with non-Hodgkin lymphoma (NHL), ranging from 42% to 75% (2,4,8,13,14,(16)(17)(18)(19)24). One series reported on patients with Waldenstrom macroglobulinemia (WM) with a 74% seroconversion rate (2).…”

Section: Main Textmentioning

confidence: 99%

“…These results of low seropositivity in some series while higher in others are likely to be related to the treatments that the patients were receiving at the time of analysis, and in particular the time since receiving therapy for the hematologic malignancy (13,25). For example, patients with NHL recently treated with anti-CD20 were less likely to develop serologic response to a COVID-19 vaccine, with the rate of seropositivity in one series being 3% in patients vaccinated within 45 days from the last anti-CD20 administration, increasing to 80% in patients vaccinated over one year after stopping this therapy (18). Patients with NHL and CLL on BTK inhibitors also have a lower seropositivity after COVID-19 vaccination, in one series from 40% for patients on this targeted therapy to 73% for patients with the same diagnosis but being monitored for their disease without active therapy at the time of COVID-19 vaccination (23).…”

Section: Main Textmentioning

confidence: 99%

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How to Provide the Needed Protection from COVID-19 to Patients with Hematologic Malignancies

Ribas

Dhodapkar

Campbell

et al. 2021

Blood Cancer Discovery

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Summary: Patients with hematologic malignancies are particularly vulnerable to COVID-19 infections, and upon a pooled data analysis of 24 publications, there is evidence that they have suboptimal antibody responses to COVID-19 vaccination and boosters. To provide them the needed additional protection from COVID-19, it is imperative to achieve a 100% full immunization rate in health care workers and adult caretakers, and to foster research to test higher doses and repeated rounds of COVID-19 vaccines and the use of passive immune prophylaxis and therapy.

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“…Study characteristics of the included publications [6][7][8][9][10][11][12][13][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] are summarized in Table 1. Information to assay details of antibody detection and CMI are indicated in Supplementary Appendix, pp.…”

Section: Study Characteristicsmentioning

confidence: 99%

Humoral and cellular immune responses upon SARS-CoV-2 vaccines in patients with anti-CD20 therapies: A systematic review and meta-analysis of 1342 patients

Schietzel

Anderegg

Limacher

et al. 2021

Preprint

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Background Immune responses upon SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously treated with anti-CD20 antibodies. Methods We searched PubMed, EMBASE, Medrxiv and SSRN using variations of search terms 'anti-CD20', 'vaccine' and 'COVID' and included original studies up to August 21st,2021. We excluded studies with missing data on humoral or cell-mediated immune response, unspecified methodology of response testing, unspecified timeframes between vaccination and blood sampling or low number of participants (n<=3). We excluded individual patients with prior SARS-CoV-2 infection or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Pre-specified subgroups were time of vaccination after anti-CD20 therapy (< vs > 6 months), time point of response testing after vaccination (< vs > 4 weeks) and disease entity (autoimmune vs cancer vs renal transplant). We used random-effects models of proportions. Findings Ninety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.41 (95% CI 0.35-0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.47-0.90). Longer time interval since last anti-CD20 therapy was associated with higher humoral response rates > 6 months 0.63 (95% CI 0.53-0.72) vs < 6 months 0.2 (95% CI 0.03-0.43); p = 0.001. Compared to patients with haematological malignancies or autoimmune diseases, anti-CD20 treated kidney transplant recipients showed the lowest vaccination response rates. Interpretation Patients on anti-CD20 therapies can develop humoral and cell-mediated immune responses after SARS-CoV-2 vaccination, but subgroups such as kidney transplant recipients or those with very recent B-cell depleting therapy are at high risk for non-seroconversion and should be individually assessed for personalized SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers, heterogeneous diseases and assays used. Funding This study was funded by Bern University Hospital.

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Humoral serological response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD2O antibodies

Cited by 54 publications

References 30 publications

A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study

A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study

How to Provide the Needed Protection from COVID-19 to Patients with Hematologic Malignancies

Humoral and cellular immune responses upon SARS-CoV-2 vaccines in patients with anti-CD20 therapies: A systematic review and meta-analysis of 1342 patients

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