In reality, prior therapy with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) seems to enhance outcomes in allo-HCT sufferers, mentioned Miguel-Angel Perales, MD, chief of the grownup bone marrow transplant service at Memorial Sloan Kettering Most cancers Heart in New York.
“Using allogeneic HCT is reducing for Hodgkin regardless that it’s a healing choice, and we see sufferers referred after they’ve had a number of strains of remedy,” Dr. Perales mentioned in an interview. “The lymphoma MDs have a notion that outcomes are poor, and subsequently don’t refer.”
For instance his level, Dr. Perales shared information from the EBMT database. In 2014, the registry accrued roughly 450 allo-HCT circumstances; by 2021 this had fallen to fewer than 200 procedures.
Satirically, this declining enthusiasm for transplantation coincides with a gradual enchancment in transplant outcomes following PD-1 blockade, Dr. Perales famous. For instance, an evaluation, revealed in Nature, yielded an 82% total survival (OS) at 3 years in sufferers who underwent allo-HCT after CPI therapy (n =209).
“Outcomes of allo-HCT in sufferers with Hodgkin present a exceptional treatment price,” mentioned Dr. Perales. “A part of that’s most likely pushed by decrease relapse on account of enhanced graft-versus-lymphoma impact on account of lengthy CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)
On the EBMT assembly, Dr. Perales offered a brand new retrospective evaluation that examined the speculation that CPIs may really enhance outcomes for allo-HCT sufferers. A world crew of clinicians from EBMT and the Heart for Worldwide Blood and Marrow Transplant Analysis (CIBMTR) in contrast allo-HCT outcomes with (n = 347) and with out (n = 1,382) prior therapy with a checkpoint inhibitor.
They discovered that prior CPI remedy was, certainly, related to decrease relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).
Nevertheless, prior PD-1 medication supplied no survival benefit, Dr. Perales mentioned. “The simplest clarification for a examine displaying a distinction in PFS/relapse, not OS, is that we’ve got good therapies that may deal with sufferers who relapse and so their total survival finally ends up being the identical.”
The researchers additionally confirmed earlier experiences that sufferers who acquired PD-1 inhibitors previous to transplant had the next incidence of GVHD. Prevalence of acute grades 2-4 GVHD was considerably increased (P = .027); nonetheless, acute grades 3-4 GVHD and power GVHD weren’t considerably completely different between the 2 teams.
Dr. Perales speculated that using posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the danger of GVHD related to PD-1 inhibitors, “we’ve got not but confirmed that formally … [we] are nonetheless analyzing our information.”
Commenting on the outcomes of the brand new evaluation, Dr. Perales expressed concern that sufferers are being recruited to early-phase medical trials after failing on a checkpoint inhibitor, as a substitute of being supplied allo-HCT – a probably healing therapy – as a result of treaters are misinformed concerning the security of transplant after these medication.
Thebacks up Dr. Perales’ worries. In the USA, for instance, there are presently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma sufferers previous to transplant. Of those, 15 research allow enrollment of sufferers who’ve failed on CPIs, and eight are part 1 or 2 research.
“The excellent news is that new medication, together with CPIs, have dramatically modified outcomes on this illness and that fewer sufferers now want an allo-HCT,” mentioned Dr. Perales. And if a transplant is required, “it’s protected to carry out allo-HCT in sufferers handled with prior CPI.”
Nevertheless, time is of the essence. “Sufferers with Hodgkin lymphoma must be referred to allo-HCT if they aren’t responding or tolerating CPI, slightly than go on a sequence of part 1 trials,” Dr. Perales mentioned. “Median age is 32, and we must be going for a treatment, nothing much less.”
Dr. Perales reported receiving honoraria from quite a few pharmaceutical firms; serving on the info and security monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has possession pursuits in NexImmune and Omeros, and has acquired institutional analysis assist for medical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.