Opportunistic Infections Put a Damper on Belatacept After Lung Transplant

HONOLULU — Lung transplant clinicians had a rocky start using belatacept (Nulojix) for immunosuppression at one large-volume center, though they maintained that the agent could still be used to preserve renal function without affecting the patient’s graft.

Out of 388 lung transplant recipients from 2019 to 2022, there were 37 who did not tolerate nephrotoxic calcineurin inhibitors (CNI) and transitioned to a belatacept regimen that included lower doses of CNI and cell cycle inhibitors like mycophenolate mofetil and prednisone.

By 12 months, 19 individuals were still on belatacept, 12 were dead, six stopped belatacept, and three were on renal replacement therapy. Of the 12 deaths, six were attributed to opportunistic infections, reported Ariba Moin, MD, postdoctoral researcher at Norton Thoracic Institute in Phoenix, at the CHEST annual meeting hosted by the American College of Chest Physicians.

“In lung transplant recipients, use of belatacept-based [immunosuppression] led to stabilization and improvement in renal function. Reasons for discontinuation of belatacept at our institution included profound leukopenia, life-threatening infections, and worsening renal function requiring renal replacement therapy,” Moin told the audience.

“Controlled studies are required to ascertain the impact of belatacept on long-term lung allograft function, marrow suppression, and lymphoproliferative disorders post-lung transplantation,” she said.

Belatacept is established as an alternative to CNI-based immunosuppression after kidney transplantation, whereas the evidence for its use in lung transplantation is more limited.

“To our knowledge, this is the largest cohort to date to utilize belatacept as a CNI-sparing agent in order to protect renal function without deterring graft function,” Moin said.

CHEST session moderator Kevin Chan, MD, of University of Michigan, Ann Arbor, commented that he’d previously seen “very alarming” data suggesting belatacept to not be as effective as CNI and that his own center’s outcomes with the drug have not been good.

“Our group unitedly continues to show interest in pursuing belatacept when appropriate to this date,” said study co-author Ashwini Arjuna, MD, lung transplant pulmonologist also at Norton Thoracic Institute.

“We started using belatacept in 2019 and we still continue to use it,” she explained, saying their experience has allowed them to foresee risks early on in order to make changes “as needed to continue belatacept [with the goal] of salvaging the kidneys with no detrimental effect on graft function.”

Such changes to the belatacept protocol include lower dosing based on patient profile and tapering down tacrolimus dosing when renal function worsens, Arjuna told MedPage Today via email.

Moin and colleagues had performed a retrospective chart review at their center for the present report.

Arjuna explained that patients whose creatinine doubled immediately with CNI were top candidates for a switch to belatacept, as were people who experienced tremors, seizures, worsening kidney function despite adjusted medications, and uncontrolled hypertension.

The switch usually occurred within a month of transplant. Some people with pre-existing renal dysfunction were identified for initiation of belatacept as soon as possible.

On this immunosuppressant drug, mean serum creatinine trended downward from 2.26 at belatacept initiation to 1.87 at 12 months.

Lung allograft function did not change since patients were put on belatacept.

Nearly half of the 37 belatacept users had positive bronchoalveolar lavage cultures — most commonly aspergillus (22.2%), pseudomonas (22.2%), and mycobacterial species (12.8%). Three people developed cytomegalovirus viremia, COVID-19 pneumonia, and BK viremia, respectively.

White blood cell count and neutrophil count tended to go down after belatacept initiation. Moin reported that five people were switched back to CNI-based immunosuppression with lowered cell cycle inhibitor dosing due to profound leukopenia.

“It is quite hard to say if belatacept actually causes new bone marrow suppression or it’s a silent bystander,” Arjuna said, adding that this is the next phase of the investigators’ research.

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