Giving steroids to sufferers with relapsed/refractory high-grade B-cell non-Hodgkin’s lymphoma (B-NHL) following chimeric antigen receptor (CAR) T-cell remedy could place them at considerably elevated danger of an infection, suggests a real-world evaluation of UK affected person information.
The evaluation additionally indicated that sufferers who’ve undergone a number of prior strains of chemotherapy are additionally at specific danger after receiving the remedy.
The analysis was offered on the digital 62nd ASH Annual Assembly and Exposition on December 7.
Dr Lorna Neill, Division of Haematology, College Faculty London Hospitals NHS Basis Belief, and colleagues appeared on the data of 60 high-grade B-NHL sufferers given CAR-T cell remedy, greater than a 3rd of whom had obtained not less than three prior strains of remedy.
Nearly half of the sufferers developed an an infection inside 30 days of receiving remedy, the bulk bacterial in nature. Over half additionally developed cytokine launch syndrome (CRS) and 1 / 4 extreme immune effector cell-associated neurotoxicity syndrome (ICANS).
Evaluation confirmed the chance of an infection following CAR T-cell remedy was elevated 4.3-fold in sufferers who had obtained not less than three prior strains of remedy, whereas steroid use elevated the chance by an element of three.8.
Presenting the outcomes, Dr Neill stated that the speed of early infections post-CAR T-cell infusion is “comparable with different cohorts”.
Nevertheless, she famous that, “not like in some US centres, this cohort didn’t obtain prophylactic antibiotics or intravenous immune globulin”.
Dr Neill continued: “Clearly, sufferers with superior illness with high-grade lymphoma are at high-risk for CRS and ICANS, which will increase using steroids and seems to result in infectious problems,” Dr Neill added.
“Heavy pre-treatment can also enhance the dangers by intensifying immunosuppression previous to CAR T-cell remedy”, and “methods to modulate these dangers embrace optimisation of [chemotherapy] bridging to scale back the illness burden…mixed with infectious prophylaxis from referral till not less than 3 to six months post-infusion.”
She stated: “On this evaluation, steroids signify a big danger and efforts ought to be made to wean doses swiftly,” whereas using steroid-sparing brokers “could also be essential and scientific trial outcomes are awaited”.
Dr Catherine Diefenbach, director, Scientific Lymphoma Program at NYU Langone’s Perlmutter Most cancers Middle, New York, USA, who was not concerned within the research, instructed Medscape Information UK that infections post-CAR T-cell remedy “is a real-world problem”.
Nevertheless, she stated that it “maybe wasn’t as distinguished when CAR T-cells had been restricted to specialised centres,” and is “one thing we’re positively going to have to observe,” as CAR T-cells have “not insignificant up-front toxicity” resulting from ICANS and CRS.
Dr Diefenbach additionally famous that it appears from the research that “there are some methods to risk-stratify and probably prophylax these sufferers”.
Extra importantly, the outcomes are “another excuse to argue towards extended doses of steroids”, she stated, including that prophylactic antibiotics could probably be of use in notably high-risk sufferers.
The CD19-targeting CAR T-cell therapies tisagenlecleucel (Kymriah, Novartis) and axicabtagene ciloleucel (Yescarta, Gilead) have been authorised to be used on the NHS for high-grade B-NHL since December 2018.
Dr Neill stated that toxicities equivalent to CRS and ICANS are “effectively reported” however “it’s changing into extra appreciated that this group of sufferers additionally expertise a big diploma of an infection,” though reported charges differ.
To research additional, the crew checked out all infections in sufferers handled with licensed CAR T-cell at their establishment between Might 2019 and July 2020, dividing them into those who occurred inside 30 days and 30 days or later following infusion.
They outlined infections primarily based on optimistic microbiological or virological outcomes plus scientific signs or, within the case of invasive fungal infections, on the revised EORTC standards, grading them as delicate, extreme or life-threatening.
The research included 60 adults with high-grade B-NHL, who had a median age of 60 years. Thirty-five p.c had been feminine. Thirty-seven p.c of sufferers had obtained not less than three prior strains of chemotherapy.
Dr Neill identified that the overwhelming majority (90%) of the sufferers required bridging remedy, over half of whom didn’t reply. So, “unsurprisingly, over two thirds of sufferers had superior stage illness pre-lymphodepletion and 1 / 4…had cumbersome illness”.
“This highlights the refractory and high-risk nature of those sufferers.”
Inside 30 days of CAR T-cell remedy infusion, 40 episodes of an infection had been recorded in 28 (47%) sufferers, whereas 27 episodes occurred in 13 (22%) at 30 days or past.
Extreme infections had been noticed in 15% of sufferers, whereas 12% had life-threatening infections, whereas in 28% of instances the an infection was delicate.
Within the majority of instances, the infections had been bacterial or respiratory viral, with bacterial infections extra doubtless inside 30 days of remedy infusion and respiratory viral infections extra generally seen later.
Dr Neill stated that CRS was “widespread”, with 52% of sufferers experiencing grade 2/3 CRS, and 57% required one dose of tocilizumab, however “few requiring steroids”, at 8%.
As well as, ICANS grade 3–5 was reported in 25% of sufferers, with 28% requiring steroids for any grade of ICANS.
Bacterial infections had been “clustered round steroid remedy,” Dr Neill added, as had been early viral reactivations.
Multivariate evaluation confirmed that danger components considerably related to any an infection post-CAR T-cell infusion had been stage ≥3 pre-lymphodepletion, at an odds ratio of 4.2 (p=0.023) and steroid use, at an odds ratio of three.3 (p=0.049).
Threat components considerably related to an infection occurring lower than 30 days post-infusion had been not less than three prior strains of remedy, at an odds ratio of 4.3 (p=0.021), and steroid use, at an odds ratio of three.8 (p=0.03).
There was no affiliation between CRS and the chance of an infection, nor with using tocilizumab.
No funding declared.
Neill declares Novartis: Different: Funded attendance at tutorial conferences; Celgene: Different: Funded attendance at tutorial conferences.
62nd ASH Annual Assembly and Exposition: Summary 3274. Introduced 7 December.
Blood 2020; 136 (Complement 1): 20–21. doi: 10.1182/blood-2020-138865