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Credit: Chad McNeeley
Adding the interleukin 6 (IL-6) inhibitor tocilizumab can improve standard prophylaxis for graft-vs-host disease (GVHD), researchers have reported in The Lancet Oncology.
IL-6 is the main detectable and dysregulated cytokine secreted after allogeneic stem cell transplant (allo-SCT).
So the researchers theorized that inhibiting IL-6 with tocilizumab might protect patients from acute GVHD despite robust immune reconstitution.
In their phase 1/2 study, the team saw acute GVHD drop from the usual 50% observed in patients receiving standard GVHD prophylaxis to 12% in patients receiving tocilizumab.
“Severe cases—which often result in death—were reduced from 21% to 4%,” said Geoff Hill, MD, of QIMR Berghofer Medical Research Institute in Brisbane, Queensland, Australia.
He and his colleagues enrolled 48 patients in this study. They ranged in age from 18 to 65 and underwent T-replete, HLA-matched, allo-SCT from unrelated or sibling donors. Patients received either total-body-irradiation-based myeloablative conditioning or reduced-intensity conditioning.
As GVHD prophylaxis, patients received a single intravenous dose of tocilizumab (8 mg/kg, capped at 800 mg, over a 60-minute infusion) the day before transplant.
They also received standard GVHD prophylaxis—cyclosporin (5 mg/kg per day on days −1 to +1, then 3 mg/kg per day to maintain therapeutic levels [trough levels of 140-300 ng/mL] for 100 days) and methotrexate (15 mg/m2 on day 1, then 10 mg/m2 on days 3, 6, and 11).
The primary endpoint was the incidence of grade 2-4 acute GVHD at day 100, which was 12%. The incidence of grade 3-4 acute GVHD was 4%.
Five patients (10%) had grade 2-4 acute GVHD involving the skin, and 4 (8%) had grade 2-4 acute GVHD involving the gastrointestinal tract. None of the patients had GVHD involving the liver.
The researchers noted that the rate of grade 2-4 acute GVHD was low regardless of the conditioning regimen a patient received. The rate was 12% for both myeloablative and reduced-intensity conditioning.
In addition, patients’ immune reconstitution was preserved after receiving tocilizumab, but the researchers did observe suppression of known pathogenic STAT3-dependent pathways.
These results represent a significant advance in allo-SCT, according to study author Glen Kennedy, MBBS, also of QIMR Berghofer Medical Research Institute.
“The new therapy has the potential to make transplant safer,” he said, “and applicable to a larger group of patients.”
A phase 3 study of tocilizumab as GVHD prophylaxis is now underway. The drug is currently approved to treat rheumatoid arthritis. 
Credit: Chad McNeeley
Adding the interleukin 6 (IL-6) inhibitor tocilizumab can improve standard prophylaxis for graft-vs-host disease (GVHD), researchers have reported in The Lancet Oncology.
IL-6 is the main detectable and dysregulated cytokine secreted after allogeneic stem cell transplant (allo-SCT).
So the researchers theorized that inhibiting IL-6 with tocilizumab might protect patients from acute GVHD despite robust immune reconstitution.
In their phase 1/2 study, the team saw acute GVHD drop from the usual 50% observed in patients receiving standard GVHD prophylaxis to 12% in patients receiving tocilizumab.
“Severe cases—which often result in death—were reduced from 21% to 4%,” said Geoff Hill, MD, of QIMR Berghofer Medical Research Institute in Brisbane, Queensland, Australia.
He and his colleagues enrolled 48 patients in this study. They ranged in age from 18 to 65 and underwent T-replete, HLA-matched, allo-SCT from unrelated or sibling donors. Patients received either total-body-irradiation-based myeloablative conditioning or reduced-intensity conditioning.
As GVHD prophylaxis, patients received a single intravenous dose of tocilizumab (8 mg/kg, capped at 800 mg, over a 60-minute infusion) the day before transplant.
They also received standard GVHD prophylaxis—cyclosporin (5 mg/kg per day on days −1 to +1, then 3 mg/kg per day to maintain therapeutic levels [trough levels of 140-300 ng/mL] for 100 days) and methotrexate (15 mg/m2 on day 1, then 10 mg/m2 on days 3, 6, and 11).
The primary endpoint was the incidence of grade 2-4 acute GVHD at day 100, which was 12%. The incidence of grade 3-4 acute GVHD was 4%.
Five patients (10%) had grade 2-4 acute GVHD involving the skin, and 4 (8%) had grade 2-4 acute GVHD involving the gastrointestinal tract. None of the patients had GVHD involving the liver.
The researchers noted that the rate of grade 2-4 acute GVHD was low regardless of the conditioning regimen a patient received. The rate was 12% for both myeloablative and reduced-intensity conditioning.
In addition, patients’ immune reconstitution was preserved after receiving tocilizumab, but the researchers did observe suppression of known pathogenic STAT3-dependent pathways.
These results represent a significant advance in allo-SCT, according to study author Glen Kennedy, MBBS, also of QIMR Berghofer Medical Research Institute.
“The new therapy has the potential to make transplant safer,” he said, “and applicable to a larger group of patients.”
A phase 3 study of tocilizumab as GVHD prophylaxis is now underway. The drug is currently approved to treat rheumatoid arthritis.
Credit: Chad McNeeley
Adding the interleukin 6 (IL-6) inhibitor tocilizumab can improve standard prophylaxis for graft-vs-host disease (GVHD), researchers have reported in The Lancet Oncology.
IL-6 is the main detectable and dysregulated cytokine secreted after allogeneic stem cell transplant (allo-SCT).
So the researchers theorized that inhibiting IL-6 with tocilizumab might protect patients from acute GVHD despite robust immune reconstitution.
In their phase 1/2 study, the team saw acute GVHD drop from the usual 50% observed in patients receiving standard GVHD prophylaxis to 12% in patients receiving tocilizumab.
“Severe cases—which often result in death—were reduced from 21% to 4%,” said Geoff Hill, MD, of QIMR Berghofer Medical Research Institute in Brisbane, Queensland, Australia.
He and his colleagues enrolled 48 patients in this study. They ranged in age from 18 to 65 and underwent T-replete, HLA-matched, allo-SCT from unrelated or sibling donors. Patients received either total-body-irradiation-based myeloablative conditioning or reduced-intensity conditioning.
As GVHD prophylaxis, patients received a single intravenous dose of tocilizumab (8 mg/kg, capped at 800 mg, over a 60-minute infusion) the day before transplant.
They also received standard GVHD prophylaxis—cyclosporin (5 mg/kg per day on days −1 to +1, then 3 mg/kg per day to maintain therapeutic levels [trough levels of 140-300 ng/mL] for 100 days) and methotrexate (15 mg/m2 on day 1, then 10 mg/m2 on days 3, 6, and 11).
The primary endpoint was the incidence of grade 2-4 acute GVHD at day 100, which was 12%. The incidence of grade 3-4 acute GVHD was 4%.
Five patients (10%) had grade 2-4 acute GVHD involving the skin, and 4 (8%) had grade 2-4 acute GVHD involving the gastrointestinal tract. None of the patients had GVHD involving the liver.
The researchers noted that the rate of grade 2-4 acute GVHD was low regardless of the conditioning regimen a patient received. The rate was 12% for both myeloablative and reduced-intensity conditioning.
In addition, patients’ immune reconstitution was preserved after receiving tocilizumab, but the researchers did observe suppression of known pathogenic STAT3-dependent pathways.
These results represent a significant advance in allo-SCT, according to study author Glen Kennedy, MBBS, also of QIMR Berghofer Medical Research Institute.
“The new therapy has the potential to make transplant safer,” he said, “and applicable to a larger group of patients.”
A phase 3 study of tocilizumab as GVHD prophylaxis is now underway. The drug is currently approved to treat rheumatoid arthritis.