Low Antibody-Mediated Responses to mRNA COVID-19 Vaccine Observed in CLL, Elderly Myeloma


The BNT162b2 mRNA COVID-19 vaccine may demonstrate decreased efficacy in patients with certain types of hematologic cancers, such as chronic lymphocytic leukemia and multiple myeloma.

The BNT162b2 mRNA COVID-19 vaccine may demonstrate decreased efficacy in patients with certain types of hematologic cancers, such as chronic lymphocytic leukemia (CLL) and multiple myeloma, according to data from 2 studies recently published in Blood.1

In a study (NCT04746092) that looked at mRNA COVID-19 vaccines specifically in patients with CLL, patients were found to have lower immune response rates vs healthy individuals with similar baseline characteristics. Overall, of the 167 patients with CLL observed on this study, 39.5% (n = 66) demonstrated a positive antibody-mediated response to the vaccine vs 100% of the healthy patients.

Additionally, immune responses differed based on where a patient was in their treatment journey. Among patients who were actively undergoing treatment, the response rate was only 16.0% (n = 12/75) compared with 79.2% (n = 19/24) in those who had completed treatment and were in remission. Moreover, treatment-naïve patients experienced a response rate of 55.2% (n = 23/58). Additionally, those who had completed treatment for CLL at least 1 year prior to receiving their mRNA COVID-19 vaccination reported a serologic response rate of 94.1% vs 50.0% in those who completed treatment less than 1 year prior (P = .04).2

"Overall, the response rate to the vaccine was significantly less than what we see in the general population, which is most likely attributed to the presence of cancer itself and certain CLL treatments," lead study author Yair Herishanu, MD, associate professor in hematology and head of the CLL service at the Tel Aviv Sourasky Medical Center in Israel, stated in a press release. "It would seem that if [a patient is] untreated, in what we call 'watch and wait,' or do not have active disease, [they] can gain more benefit from the vaccine. Patients who responded the best were in remission, which makes sense because their immune system had a chance to recover."

Patients with CLL and other hematologic malignancies are at increased risk for severe illness and complications from COVID-19 infection. As such, investigators sought to determine the efficacy of available mRNA COVID-19 vaccines in this patient population compared with age-matched healthy controls. They also set out to determine the most optimal time during treatment to get vaccinated.

Patients aged 18 years or older with confirmed CLL or multiple myeloma and no known history of COVID-19 infection were eligible to participate on the study. The trial also included healthy volunteers who were at least 18 years of age; these patients served as the control group.

In total, 167 patients with CLL and 52 age- and sex-matched controls were enrolled to the study and were vaccinated. Patients received 2 doses of the mRNA Pfizer COVID-19 vaccine 21 days apart. Antibody levels were then measured using the Elecsys Anti- SARS-CoV-2S assay 2 to 3 weeks after the second dose of the vaccine was administered.

The primary end point of the study was the proportion of patients who acquired COVID-19 antibodies, and secondary end points included COVID-19 morbidity rates, documentation of vaccine-related adverse effects (AEs), and comparison of immune response in patients with CLL vs healthy individuals.3

The median age of study participants was 71 years (range, 63-76), and 67.1% were male (n = 112/167). Among the patients with CLL, 34.7% (n = 58) were treatment naïve, 44.9% (n = 75) were on active therapy, 14.4% (n = 24) were previously treated and in remission, and 6% (n = 10) were previously treated and in relapse. Additionally, among the patients who had received treatment for CLL, 66.7% received prior therapy with a BTK inhibitor and 29.3% had received treatment with venetoclax (Venclexta) with or without an CD20-targeted antibody.

Results from a multivariate analysis revealed that independent predictors of response included included younger age, female sex, early disease stage, and lack of active therapy. Moreover, the response rates achieved by patients who previously received treatment with a BTK inhibitor was 16.0% (n = 8/50) and 13.6% (n = 3/22) in those who previously received venetoclax with or without CD20-targeted antibodies.

In terms of safety, mild, local AEs such as injection site pain, erythema, or swelling were reported in 31.1% of patients (n = 52/167) following their first dose of the vaccine, and 33.5% (n = 56) after their second dose. Systemic AEs were reported in 12.5% (n = 21) of patients after their first dose and 23.4% (n = 39) following their second dose.

All reported AEs were mild in severity, and the most common included weakness (6.6%), headache (5.4%), fever (2.4%) and muscle pain (1.8%) after the first dose. After the second dose, the most frequent AEs reported included weakness (8.6%), fever (6.6%), chills (6.0%), headache (5.4%) and muscle pain (4.8%).

"Although response rates were not optimal, patients with CLL should still receive the vaccine and, if appropriate, it may be better to do so before CLL treatment starts although the disease itself may affect the response," Herishanu noted. "Equally important is continuing to take precautions—wearing a mask, avoiding crowds, keeping a social distance, and being sure that close contacts get vaccinated against COVID-19."

Similarly, in another study (NCT04743388) that examined elderly patients with multiple myeloma who had received the first dose of the same vaccine, immune response rates were also lower compared with those observed in healthy-control patients.

In this study, antibody levels were tested in 48 elderly patients with multiple myeloma and 104 healthy individuals 22 days after the first dose of the mRNA COVID-19 vaccine was received, and prior to the second dose. Among these patients, immune responses were experienced by 20.6% of patient with multiple myeloma vs 32.5% in healthy patients.4

Among the 48 patients with multiple myeloma enrolled to the study, the median age was 83 years (range, 59-92). Thirty-five patients were actively receiving anticancer treatment, 4 were in remission, and 9 had smoldering myeloma.

Investigators concluded that larger studies are needed to solidify the findings reported and that the timely administration of a second dose of the mRNA COVID-19 vaccine is essential to developing an adequate antibody response in this patient population.


  1. Studies suggest people with blood cancers may not be optimally protected after COVID-19 vaccination. News release. American Society of Hematology. April 16, 2021. Accessed April 27, 2021. https://bit.ly/3aJ8XZG
  2. Herishanu Y, Avivi I, Aharon A, et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood. 2021;137(23):3165-3173. doi:10.1182/blood.2021011568
  3. The capability of haemato-oncology patients to generate antibodies against COVID-19. ClinicalTrials.gov. Updated February 9, 2021. Accessed April 27, 2021. https://clinicaltrials.gov/ct2/show/NCT04746092
  4. Terpos E, Trougakos I, Gavriatopoulou M, et al. Low neutralizing antibody responses against SARS-CoV-2 in elderly myeloma patients after the first BNT162b2 vaccine dose. Blood. 2021;137(26):3674-3676. doi:10.1182/blood.2021011904
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