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Università Vita-Salute San Raffaele
Strategic Research Program on CLL
Lydia Scarfò, MD, has disclosed that she has received consulting fees from AbbVie, AstraZeneca, and Janssen.
Since the first COVID-19 cases were reported in December 2019, SARS-CoV-2 has caused more than 4 million deaths worldwide. Older individuals and those with certain comorbidities (eg, diabetes, cardiovascular and respiratory diseases, solid and hematologic malignancies) appear to be at higher risk of poor outcomes if infected. Unfortunately, patients with hematologic malignancies—including chronic lymphocytic leukemia (CLL)—have a mortality rate as high as 37% if hospitalized due to COVID-19.
Given the limited availability of effective treatments for COVID-19, the best strategy to protect our patients with CLL is to vaccinate against SARS-CoV-2 infection. But how effective are the mRNA vaccines against COVID-19 in patients with CLL, who frequently exhibit compromised immune responses due to both their disease and treatment?
Efficacy of Pfizer-BioNTech BNT162b2 mRNA COVID-19 Vaccine in Patients With CLL
With lead author Dr. Yair Herishanu of Tel Aviv University, my colleagues and I reported the results of a prospective study that enrolled 167 patients with CLL without any history of SARS-CoV-2 infection who received 2 doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine through the national Israeli vaccination program. The overall seroconversion rate was 39.5%. In a subanalysis of slightly younger patients, the seroconversion rate was 52%—disappointingly lower than the 100% rate observed in gender-matched and age-matched controls. These findings were comparable to the 52% seroconversion rate recently reported in a US study of 44 patients with CLL.
In the Israeli report, a multivariate analysis found a higher probability of serologic response in patients aged 65 years or younger, female sex, lack of active therapy, IgG levels ≥550 mg/dL, and IgM levels ≥40 mg/dL. None of the patients treated with anti-CD20 antibodies in the last 12 months had a serologic response, whereas the highest seroconversion rate (79.2%) was observed in 24 patients who had been previously treated and were in response at the time of vaccination. The US study also observed that previously untreated patients and those aged younger than 70 years were more likely to produce anti–SARS-CoV-2 S1/S2 antibodies.
The poor humoral response in patients with CLL comes as no surprise considering that previous studies have shown low rates of response to the pneumococcal conjugated vaccine, influenza A and B vaccines, and hepatitis B (HepB-CpG) vaccine in patients with CLL, particularly those on treatment. That being said, a higher seroconversion rate has been observed when patients are exposed to “recall antigens” (eg, varicella zoster), even in those receiving treatment with BTK inhibitors.
These initial results on the Pfizer-BioNTech BNT162b2 mRNA vaccine in patients with CLL prompt some considerations for clinical practice. First, the analyses mostly focused on seroconversion rate and do not provide information on T-cell response to SARS-CoV-2 vaccination and the occurrence and persistence of SARS-CoV-2 memory B-cells. Thus, we do not know yet if our patients with CLL and low to undetectable antibody titers have developed any sort of protection. Further studies are warranted to understand this issue.
Second, if standard vaccination protocols are not enough to gain immunity in patients with CLL, we need to evaluate strategies that may safely improve the response rates. One strategy may be to better define vaccination timing. In patients with progressive disease requiring treatment, every effort should be made to complete vaccination before starting therapy, even though active disease can hamper immune response. In patients receiving or having received treatment with anti-CD20 antibodies, we should consider postponing vaccine administration until 12 months after the last dose, particularly in regions where community SARS-CoV-2 prevalence is declining. Needless to say, it is also crucial to vaccinate household contacts to take advantage of the “familial” herd immunity.
Third, as we have seen with other vaccines, potential strategies to improve vaccine efficacy include booster doses, use of different vaccine types (as for pneumococcal vaccine), and the addition of adjuvants (eg, varicella zoster recombinant adjuvanted vaccine). There are no data so far on COVID-19 vaccines in patients with CLL with any of these strategies, but encouraging early data have recently been published on a small series of solid organ transplant recipients on immunosuppressive treatment. This study suggested a limited improvement in seroconversion with administration of a third vaccination dose, with 6 out of 24 (25%) patients with previously negative antibody titers increasing to high titers after the third dose. Although the third dose was generally well tolerated, 1 patient experienced biopsy-proven, antibody-mediated heart transplant rejection 7 days after her third dose.
We will have to wait for the results of prospective trials including immunocompromised patients to test immunogenicity, safety, and strategies to boost response with COVID-19 vaccines. In the meantime, we must rely on herd immunity and counsel patients with CLL to maintain extreme caution even after vaccination until more comprehensive data are gathered.
Do you still have questions on COVID-19 vaccination in patients with hematologic malignancies? Register today to join multidisciplinary experts John Allan, MD, and Sandra E. Kurtin, PhD, ANP-C, AOCN, for a highly interactive webinar featuring a short presentation on the latest clinical data on COVID-19 vaccination in patients with lymphomas, followed by a question and answer session with the healthcare professional audience.