Good Response to COVID-19 Vaccine After HSCT and CAR T-cell Tx

Nancy A. Melville

June 16, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Patients with blood cancers are particularly vulnerable to COVID-19, and there has been concern that such patients mount poor responses to COVID vaccination.

Perhaps surprising, then, is a new study showing good responses in a subgroup of these patients who underwent intensive treatment with allogeneic hematopoietic stem cell transplant (HCT) or chimeric antigen receptor T-cell (CAR-T) therapy

These patients had relatively good responses to COVID-19 vaccination with the mRNA vaccine, with overall cellular and humoral responses that were near to or over 80%.

"I was actually surprised by the fact patients who underwent allogeneic HCT and are currently treated with immunosuppression medications had a such high response to the vaccine," first author Ron Ram, MD, director of the Bone Marrow Transplantation Unit, Division of Hematology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel, told Medscape Medical News.

"In other seasonal vaccines, we usually see much lower responses," he noted. "The problem is that we are not sure how long this response lasts, and this should be further investigated."

The results show that among immunocompromised patients, "the vaccine is safe and efficacious," he concluded.

However, "5% of patients developed transient severe low counts and graft-vs-host disease [GVHD] exacerbation. Therefore, close monitoring of these patients is mandatory.

"COVID-19 is a very dangerous infection to our allogeneic and CAR-T patients, and all patients should be vaccinated as soon as possible," he added.

The study was presented at the European Hematology Association (EHA) 2021 Annual Meeting. It involved 79 eligible patients who received hematopoietic cell transplant (n = 66) and CAR T-cell therapy (n = 14) at the Tel Aviv Sourasky Medical Center.

The patients in the study were being treated for acute myeloid leukemia (46%), myelodysplastic syndromes (9%), acute lymphocytic leukemia (10%), diffuse large B-cell lymphoma (15%); and others.

All patients were vaccinated with the Pfizer/BioNTech BNT162b2 COVID-19 vaccine, which yielded a protection rate of 94.6% in a phase 3 study in healthy patients and is recommended for immunosuppressed patients.

The median age of the patients was 65 years, and the median time from infusion of cells to vaccination was 32 months in the allogeneic HCT group and 9 months in the CAR T-cell therapy group.

Of the allogeneic HCT patients, 62% had active chronic GVHD, and 58% were receiving immune suppressive therapy, mostly calcineurin inhibitors.

In addition, 11% of the patients overall had complete B-cell aplasia.

An evaluation of humoral immune responses to the vaccines at 7 to 14 days after the second vaccine dose, as determined on the basis of serology, showed that 82% of those in the allogeneic HCT group developed immunogenicity. However, the humoral response rate was only 36% in the CAR T-cell group.

When including the results cellular responses, assessed with the ELISpot assay, the tables were nearly turned, with the antibody titer response rate of 46% in the allogeneic HCT group and 79% in the CAR T-cell group.

Combined, the overall antibody responses were 86% of allogeneic HCT patients and 79% of CAR T-cell patients, Ram reported.

A multivariate analysis showed that factors associated with a positive humoral response included increased amount of time from the infusion of cells (P = .032), female sex (P = .028), and a higher number of CD19-positive cells (P = .047).

Age, active GVHD, and the intensity of concomitant immunosuppressive therapy were not predictive of results.

Ram noted that higher numbers of CD19-positive cells and CD4 cells were predictive of positive ELISpot cellular response (P = 0.49 and P = .041, respectively).

Two patients developed SARS-CoV-2 infection after receiving the first dose of the vaccine, although they did not require hospitalization. After fully recovering, both patients received a second dose.

The vaccine was well tolerated among patients in general. Side effects were similar to those observed in the nontransplant population.

Of the patients overall, 5% experienced GVHD exacerbation after each vaccine dose.

A low blood count was observed in about 10% of patients; in 5%, the cytopenia was severe.

Adverse events that were of grade 3 or higher occurred in 4.6% and 7% of the two groups, respectively. Although the adverse events resolved quickly in most cases, one secondary graft rejection occurred; that case is being investigated.

The European Society for Blood and Marrow Transplantation (EBMT) recommends vaccination starting at least 3 months after allogeneic HCT, and Ram said the recommendation "makes sense."

"We did see a nice response in the allogeneic HCT patients 3 months after the transplant," he said.

Exceptions were patients receiving anti-CD19 therapy in the CAR T-cell group and those with B-cell aplasia. "Those patients did not respond well to the vaccine, so this is something to take into consideration," Ram said.

"We certainly need more data about durability of the vaccine and methods in patients who do not have sufficient response to the vaccine."

The EBMT's recommendation on the timing of vaccination is endorsed by the National Comprehensive Cancer Network, which recommends that COVID-19 vaccination be delayed for at least 3 months for patients with allogeneic HCT or those undergoing CAR-T therapy.

In commenting on the study during a press conference, Elizabeth Macintyre, MD, said the new findings were encouraging.

"It's very precious to see consensus recommendations regarding who should be vaccinated and when, and the end result seems to be that it's better to be vaccinated than not," she said.

Another Report of a Low Response to Vaccination

In a separate talk at the meeting, Evangelos Terpos, MD, PhD, reported finding lower response rates to COVID-19 vaccination among older patients with hematologic malignancies in general, consistent with findings from other studies.

Reporting on responses up to day 50 post vaccination among 48 patients with multiple myeloma (median age, 83 years), 40% of patients did not achieve antibody titers above the level of 30% considered to represent positivity.

Among the 49% who did achieve antibody responses above levels of 50%, representing clinically relevant inhibition, the treatment factors that were associated with the higher response included treatment with lenalidomide. Treatment with daratumumab or anti-BCMA conjugates was associated with very low antibody responses.

He noted other research of 58 older patients with Waldenstrom macroglobulinemia or other low-grade lymphomas showed similarly low responses, particularly among those receiving anti-CD20 treatment, compared with healthy individuals.

"We found that patients with hematological malignancies or solid tumors have lower responses [to the COVID-19 mRNA vaccine], especially those under immunotherapy or targeted therapies, including anti-CD20, anti-CD38, anti-BCMA, Bruton kinase inhibitors, PDL-1 or PD-1 inhibitors," said Terpos, a professor of hematology at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece.

Ram has disclosed no relevant financial relationships. Terpos has relationships with Janssen, Genesis/Celgene, Amgen, Novartis, Sanofi, and Takeda.

European Hematology Association (EHA) 2021 Annual Meeting: Abstract S285. Presented June 11, 2021.

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