Blood cancer drug aids kidney recovery in 2 AAV patients, study shows
Researchers say larger studies needed to confirm findings
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Blinatumomab, a blood cancer treatment, improved kidney function in two people newly diagnosed with ANCA-associated vasculitis (AAV) and rapidly progressive glomerulonephritis (RPGN), or inflammation in the kidney’s filtering units, a study shows.
The therapy is designed to promote an interaction between immune T-cells, which can kill other cells, and immune B-cells, which produce antibodies, including those that drive autoimmune diseases such as AAV. Because this interaction prompts T-cells to kill B-cells, blinatumomab can potentially help control autoimmune responses.
“Together, these two cases suggest that T-cell-redirected … B-cell elimination may contribute to robust [kidney] recovery in selected AAV-RPGN patients,” researchers wrote, noting, however, that larger studies are needed to confirm these findings.
The two cases were described in the study “Blinatumomab as the first-line induction for ANCA-associated rapidly progressive glomerulonephritis,” which was published as a letter in the journal RMD Open: Rheumatic & Musculoskeletal Diseases.
Treatment type explored as strategy for certain autoimmune diseases
AAV is a group of autoimmune diseases marked by inflammation and damage to small blood vessels, and it’s typically driven by self-reactive antibodies called ANCAs. The disease can affect several organs, including the kidneys and lungs.
One of its most severe kidney complications is RPGN, which can lead to a rapid decline in kidney function. Previous data suggested that standard treatment to induce AAV remission (few to no symptoms) is associated with limited kidney function improvements in people with AAV-associated RPGN.
Administered via infusion into the bloodstream, blinatumomab is approved to treat a blood cancer associated with abnormal B-cell growth. It is a bispecific antibody that simultaneously binds to CD19 and CD3, proteins present at the surface of B-cells and T-cells, respectively, bringing the two types of immune cells together.
Because this type of treatment, called T-cell engager (TCE), can reduce B-cell counts and subsequently lower levels of self-reactive antibodies, it has been explored as a potential strategy for certain autoimmune diseases, with some promising results.
Measure of kidney function, significantly improved
In this study, a team of researchers in China described the cases of a 40-year-old man and a 50-year-old woman with newly diagnosed AAV-associated RPGN who showed positive responses to blinatumomab treatment.
Both had microscopic polyangiitis (MPA), the most common AAV type in China, and were positive for ANCAs against the myeloperoxidase protein (MPO), one of the most common targets of AAV-causing antibodies. They both showed body-wide disease activity and lung involvement.
Clinically, both patients exhibited rapid improvement in [body-wide] disease activity.
Blinatumomab was administered in the hospital as a five-day continuous into-the-vein infusion, followed by a two-day infusion two weeks later. One patient received a third cycle of blinatumomab six months later, due to elevated levels of anti-MPO ANCAs and persistent protein in the urine, a sign of kidney damage.
“Clinically, both patients exhibited rapid improvement in [body-wide] disease activity,” the researchers wrote, adding that “marked [kidney] recovery was seen in both patients.”
Specifically, estimated glomerular filtration rate (eGFR), a measure of kidney function, significantly increased (improved), by 50 mL to 65 mL/min/1.73 square meters, within two months of treatment. Protein levels in urine were also reduced. Lung lesions were resolved within four weeks, and neither patient experienced a disease relapse during up to a year of follow-up.
Blood tests showed that after the first blinatumomab cycle, B-cell counts showed a rapid decrease, and levels of antibodies dropped by about 50% to 60%.
The most common adverse event was cytokine release syndrome, a life-threatening inflammatory reaction caused by the rapid activation of immune cells, that peaked during days two to four and resolved within about three days.
Treatment may help eliminate disease-driving B-cells more effectively
The researchers proposed that blinatumomab’s mechanism of action may help eliminate disease-driving B-cells more effectively in affected tissues, including the kidneys. This could help explain the rapid reduction in ANCA levels and kidney recovery seen in the two patients.
However, the team emphasized that this remains a hypothesis because the study did not directly show that B-cells had been eliminated from the kidneys.
For comparison, the team retrospectively analyzed data from 57 people with active AAV-RPGN who were treated at their center. Most had MPA, and all had severely impaired kidney function.
Standard induction treatment with cyclophosphamide, a broad-acting immunosuppressant, or B-cell depleting therapies such as rituximab significantly reduced disease activity, but kidney recovery was more limited. eGFR increased by a mean of 15 mL/min/1.73 square meter six months after initiating therapy.
Still, because the report involved only two patients, the findings cannot establish that blinatumomab is effective for AAV-RPGN or determine its safety compared with standard treatments.
“Further large-scale clinical trials are warranted to validate the benefits of early TCE before irreversible [kidney] injury and define its optimal clinical application, efficacy and safety profile in AAV-RPGN,” the researchers concluded.
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