Blood cancer patients show poor responses to mRNA vaccine, especially with anti-CD-20 mAbs

Blood cancers

14 Jul 2021

Most people with cancer develop a good immune response after two doses of COVID-19 mRNA (Pfizer, Modena) vaccine, but those with a haematological cancer tend to be non-responders, an international study suggests.

An analysis of responses to SARS-CoV-2 mRNA vaccines in 131 cancer patients, treated at two cancer centres in the US and Switzerland found that 94% achieved seroconversion at three to four weeks after receipt of two doses.

Most of the patients in the study had solid cancers (101), while patients with haematological malignancy had significantly reduced seroconversion rates (77% versus 98%) and antibody titers (median, IQR: 832 vs > 2,500 U/ml) after the second dose compared with those with solid tumours.

Antibody titre rates were low after the first dose, highlighting the need for cancer patients to complete their full course of vaccines, said the study authors in Cancer Cell.

“We observed a significant difference in response when two doses were given,” said co-author Dr Dimpy Shah of the Mays Cancer Center, UT Health San Antonio MD Anderson.

“At least for patients with cancer, two doses are very important for robust antibody response.”

Seroconversion rates were high across all treatment subgroups, including recipients of cytotoxic therapy, immunotherapy, anti-CD38, anti-HER, anti-VEGF  and RANKL antibody therapy and kinase inhibitor therapy.

However antibody titre rates were reduced for patients receiving cytotoxic therapy (median IQR 611 vs 2,500 U/ml overall), anti-CD38 (203 U/ml) and anti-VEGF (329 U/ml).

“How [this] relates to protection against COVID-19, we don’t know yet,” Dr Shah said.

Patients receiving anti-CD20 antibody therapy did not develop any antibody response even after receiving two doses.

The study authors said this did not come as a surprise as other studies had shown rituximab could cause immunosuppression through several mechanisms to impair the response to vaccines.

“It reacts specifically with the CD20 antigen expressed on more than 95% of normal and malignant B cells, inducing complement-mediated and antibody-dependent cellular cytotoxicity,” they noted.

“Rituximab could indeed cause a rapid depletion of pre-B cells and mature B cells, which remain at low or undetectable levels for 2–6 months before returning to pretreatment levels, generally within 12 months.”

“Growing evidence supports that rituximab might influence T cell immunity as well,” they added.

The optimal approach for vaccinating and monitoring this subset of patients at high risk for non-response to SARS-CoV-2 vaccines remained unclear, but might involve a third booster dose, they suggested.

The study authors concluded that patients with haematological  cancers, especially those receiving anti-CD20 antibodies, should continue to take precautions even after being vaccinated.

“They still need to have that awareness that they could potentially be at risk because their body has not responded to vaccination,” they said.

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