Photo by Chad McNeeley
A treatment approach that combines epigenetics and immunotherapy could provide a bridge to transplant in patients with T-cell prolymphocytic leukemia (T-PLL), according to researchers.
In a pilot study, the team found that combining alemtuzumab with epigenetic agents could override alemtuzumab resistance in T-PLL.
The approach produced complete responses (CRs) in 7 of 8 patients. The eighth patient achieved a partial response (PR).
However, 5 of the patients ultimately died of persistent disease, and 2 are alive in early relapse. One patient remains in remission after allogeneic hematopoietic stem cell transplant (HSCT).
“There’s been a revolution in the last few years seeing success with immunotherapy, and people speculated that, perhaps, if you combined epigenetic and immunotherapy, that might be even more spectacular,” said Thomas P. Loughran Jr, MD, of the University of Virginia Cancer Center in Charlottesville. “This is proof of principle that this might be true.”
Dr Loughran and his colleagues described this research in Science Translational Medicine.
The researchers evaluated 8 patients with T-PLL, 4 of whom were previously untreated (patients 3, 4, 5, and 6).
Patient 2 presented with alemtuzumab-resistant disease but achieved a CR after receiving the drug along with cladribine and vorinostat. He achieved PRs with the same regimen after a second and third relapse but ultimately progressed and died.
“It was unbelievable, really, seeing a patient who had already failed [alemtuzumab] literally going back into remission,” Dr Loughran said.
Patients 1, 4, 6, and 8 achieved a CR with cladribine and alemtuzumab, and patient 3 achieved a PR on the same regimen.
Patient 7 received cladribine and alemtuzumab as well but only achieved a CR with the addition of valproic acid. Patient 5 achieved a CR with cladribine, alemtuzumab, and vorinostat.
Patients 3, 4, and 5 ultimately died. Patient 4 experienced a grade 5 intracranial hemorrhage that may have been treatment-related.
Patients 7 and 8 are in relapse, but they are receiving treatment and are under consideration for HSCT. Patient 6 went on to HSCT after achieving a CR and has been in remission for 4 years.
Major adverse events in this study include neutropenia (5 grade 4, 3 grade 3), thrombocytopenia (2 grade 4, 1 grade 3), anemia (1 grade 2, 2 grade 3), grade 3 febrile neutropenia (n=2), grade 2 lung infection (n=2), grade 1 CMV reactivation (n=1), grade 3 oral mucositis (n=1), grade 3 skin infection (n=1), and grade 5 intracranial hemorrhage (n=1).
