In a long-term follow-up of an early-phase trial inspecting CD19.28ζ chimeric antigen receptor (CAR) T-cell remedy, using consolidative allogeneic hematopoietic stem cell transplant (alloHSCT) was related to long-term and sturdy illness management in youngsters and younger adults with B-cell acute lymphoblastic leukemia (B-ALL).
These outcomes had been primarily based on a cohort of 20 sufferers who had been initially handled in a dose-escalation a part of a part 1 trial (NCT01593696) inspecting anti-CD19 CAR T-cell remedy in sufferers between 1 and 30 years who haven’t responded to straightforward therapy, plus a further 30 sufferers who had been handled in an enlargement portion. The median follow-up for all sufferers examined was 4.8 years and represents the longest time interval examined for using this remedy in youngsters and younger adults with B-ALL.
“We display that CD19.28ζ CAR T cells adopted by a consolidative alloHSCT can present long-term sturdy illness management in [child and young adult patients] with relapsed or refractory B-ALL,” wrote the examine investigators who had been led by Nirali N. Shah, MD. “Following alloHSCT, we noticed a major long-term [event-free survival (EFS)] with an obvious plateau and a low relapse price, offering help for this sequential strategy for long-term treatment.”
The entire response price (CR) was 62.0%, with 28 of the 31 sufferers reaching this finish level additionally reaching minimal residual illness (MRD) negativity by circulation cytometry. The speed of CR was increased in sufferers with main refractory illness (P = .0035), fewer prior strains of remedy (P = .033), and an M1 marrow (P = .0007). Moreover, CR charges had been higher for sufferers who acquired fludarabine/cyclophosphamide–primarily based lymphodepletion versus different regimens, at 69% and 25%, respectively (P = .041).
The median total survival (OS) for the cohort was 10.5 months (95% CI, 6.3-29.2 months). The median EFS was 3.1 months (95% CI, 0.9-7.7), with charges at 3 and 6 months of 52.0% (95% CI, 37.4%-64.7%) and 38.0% (95% CI, 24.8%-51.1%), respectively. Notably, median EFS was not reached in sufferers handled with M1 marrow versus 0.9 months in these with ≥M2 marrow (P ≤.0001).
Of the sufferers reaching MRD-negative CR (n = 28), 21 (75.0%) went on to obtain consolidative alloHSCT, with a median time to transplant of 54 days from infusion (vary, 42-97). The median OS from transplant day 0 was 70.2 months (95% CI, 10.4 months-not estimable) and the median EFS was not reached. The speed of EFS at 5 years was 61.9% (95% CI, 38.1%-78.8%). There have been 8 deaths between 0.8 and 71 months following alloHSCT, which included transplant-related problems and/or graft-versus-host illness or an infection in 6 sufferers and 1 affected person with a complication of secondary malignancy at 3 years post-transplant. Teo sufferers relapsed after alloHSCT, with a cumulative threat of relapse was 4.8% (95% CI, 0.3-20.3) and 9.5% (95% CI, 1.5%-26.8%) at 12 and 24 months, respectively, with loss of life as a competing threat.
Of be aware, reaching a CR was related to better CAR T-cell enlargement and grade 3/4 cytokine launch syndrome (CRS). General, CRS occurred in 70.0% of sufferers, with 9 (18.0%) having a grade 3/4 occasion. Neurotoxicity occurred in 10 sufferers (20.0%), with 4 having extreme neurotoxicity.
Central nervous system involvement was successfully handled with CAR T-cell remedy all sufferers with a marrow response and CRS, though 1 sufferers did have residual illness by circulation cytometry at low ranges.
The authors famous that given these findings, CD19-directed CAR T-cell remedy could also be thought-about as a bridge to alloHSCT versus standard-of-care blinatumomab (Blincyto).
“Regardless of its extra prepared availability, which isn’t depending on manufacturing time or success thereof, the efficacy of blinatumomab in youngsters is decrease than in adults receiving blinatumomab and likewise decrease than remission charges following CD19-CAR T cells, utilizing any assemble, notably for these with high-burden illness,” the examine writer wrote. “Subsequently, choice of CAR T cells over blinatumomab could also be advantageous in sufferers with higher-burden illness and [extramedullary] illness or as a salvage for blinatumomab nonresponders.”
Shah NN, Lee DW, Yates B, et al. Lengthy-Time period Comply with-Up of CD19-CAR T-Cell Remedy in Kids and Younger Adults With B-ALL. J Clin Oncol. March 25, 2021. doi: 10.1200/JCO.20.02262