The following article features coverage from the 2021 American Society of Hematology Annual Meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Double-dose mRNA COVID-19 vaccination led to a humoral response in 52% of patients with chronic lymphocytic leukemia (CLL), and a third dose induced seroconversion in 42% of those who remained seronegative after the second dose, according to study results presented at the 2021 American Society of Hematology (ASH) Annual Meeting.

Researchers assessed SARS-CoV-2 antibody responses after the first, second, and third doses of the BNT162b2 and mRNA-1273 vaccines in patients with CLL, and immunoglobulin G (IgG) antispike levels were measured 4 to 6 weeks after each vaccine dose.

A total of 530 patients and 14 control individuals were included. Patients had a median age of 71 years (range, 37-93), 218 (40%) were treatment-naive (TN), 136 (26%) had prior CLL treatment, and 176 (34%) were receiving therapy.

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Vaccine responses were evaluated after dose 1 for 158 CLL patients, after dose 2 for 506 patients, and after dose 3 for 66 patients. Peripheral blood lymphocyte subsets in 80 CLL patients and 14 controls were assessed after dose 2 with use of flow cytometry.

The global response rate was 27% (43/158) after dose 1. TN patients had a response rate of 34% (23/67), which was comparable to those with previous CLL treatment (33%,12/36) and higher compared with on-therapy patients (15%, 8/55; P =.02).

After dose 2, the global response rate was 52% (265/506). TN patients had the highest response rate of 72% (151/210) compared with previously treated patients, primarily in immunochemotherapy recipients (60%, 78/130; P =.02) and on-therapy patients (22%, 36/166; P <.001).

In the 166 on-therapy patients who mostly received targeted agents, those who received venetoclax monotherapy had a significantly higher response rate (52%, 12/23) compared with those who received ibrutinib or acalabrutinib (22%, 23/104, P <.001). Participants who received venetoclax plus anti-CD20 monoclonal antibodies (19 patients) or venetoclax plus a BTK inhibitor (6 patients) were seronegative after the second vaccine dose.

Multivariate analysis showed that the variables significantly associated with seroconversion were age older than 65 years (odds ratio [OR], 0.55; 95% CI, 0.33-0.92; P =.02), ongoing CLL treatment (OR, 0.13; 95% CI, 0.07-0.23; P <.001), and gamma-globulins less than or equal to 6 g/L (OR, 0.41; 95% CI, 0.19-0.88; P =.03).

After dose 2, seronegative patients were offered a third dose, and 66 have been tested thus far for their antibody response 4 to 6 weeks after their third dose, which was 42% (28/66). TN patients and those with previous treatment had a significantly higher response rate (57%, 16/28) vs on-therapy patients (32%, 12/38, P =.03).

Among participants who were further analyzed after dose 2 (24 patients) with a SARS-CoV-2 IgG antispike assay, those who achieved seroconversion after the third dose (10 patients) had significantly higher titers after dose 2 (median, 12; interquartile range [IQR], 3.0-40.8) compared with those who remained seronegative (14 patients; median, 2.2; IQR, 0.5-5.1; P <.01), although both median values are considered below the threshold.

In 40 patients with CLL who presented with SARS-CoV-2 infection before vaccination and were analyzed separately, all patients achieved seroconversion after infection and 1 dose of vaccine, even though 30% (12 patients) were undergoing CLL treatment.

The investigators noted that the major independent predictor of negative antibody response was ongoing treatment with a BTK inhibitor. On the other hand, the strongest boost to immune response against SARS-CoV-2 appears to be infection.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of the ASH 2021 meeting by visiting the conference page.


Bagacean C, Letestu R, Al Nawakil C, et al. Humoral response to mRNA vaccines BNT162b2 and mRNA-1273 COVID-19 in chronic lymphocytic leukemia patients. Presented at ASH 2021; December 11-14, 2021. Abstract 637.