Karilyn Larkin

The ACCESS trial is a prospective, multicenter phase 2 trial evaluating peripheral blood stem cell (PBSC) transplantation using 4/8 to 7/8 HLA-mismatched unrelated donors (MMUD) with posttransplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate. Adults undergoing first hematopoietic cell transplantation (HCT) with myeloablative conditioning or reduced-intensity conditioning (RIC)/nonmyeloablative conditioning (NMA) were enrolled. This expanded analysis includes all enrolled adult PBSC HCT recipients, including the protocol-specified RIC/NMA cohort expansion, to improve precision of outcome estimates and provide descriptive analyses by HLA-match level. Among 268 adults, 183 received 7/8 and 85 received <7/8 MMUD grafts; 82.4% of the <7/8 cohort received 6/8 MMUD grafts. Median follow-up among survivors was 11.9 months. At 1 year, overall survival was 78.6% (95% confidence interval [CI], 71.9-83.9) in the 7/8 cohort and 85.6% (95% CI, 76.0-91.5) in the <7/8 cohort. One-year relapse, nonrelapse mortality, and graft-versus-host disease (GVHD)–free relapse-free survival were 17.1%, 13.7%, and 51.1% vs 22.8%, 8.4%, and 54.6%, in the 7/8 and <7/8 cohorts, respectively. The cumulative incidence of grade II to IV and grade III to IV acute GVHD by day 100 was 36.6% and 7.7% in the 7/8 cohort vs 28.3% and 5.9% in the <7/8 cohort. Moderate-to-severe chronic GVHD at 1 year was 11.3% vs 7.7% in the 7/8 and <7/8 cohorts, respectively. Among adult ACCESS trial participants treated on a uniform young-donor PBSC/PTCy platform, short-term outcomes with predominantly 6/8 MMUD transplantation were encouraging. Because donor match level was not prospectively assigned and between-group comparisons were exploratory, these findings are descriptive and should not be interpreted as establishing equivalence with 7/8 MMUD transplantation. This trial was registered at www.clinicaltrials.gov as NCT04904588.

PURPOSE: To evaluate the efficacy and safety of the cluster of differentiation 47–targeted antibody magrolimab plus azacitidine (Magro/Aza) versus azacitidine alone in treatment-naïve patients with higher-risk myelodysplastic syndromes (MDS) in the phase III ENHANCE study (ClinicalTrials.gov identifier: NCT04313881 ). METHODS: Based on the Revised International Prognostic Scoring System, patients with intermediate- to very-high-risk MDS were randomly assigned to receive Magro (1 mg/kg on days [D]1 and 4; 15 mg/kg on D8; 30 mg/kg on D11 and D15, and then once per week for five doses, followed by 30 mg/kg maintenance doses once every 2 weeks)/Aza (75 mg/m ² daily on D1-7 or on D1-5 and 8-9 in 28-day cycles) or matched placebo plus azacitidine (Placebo/Aza). Dual primary end points were complete remission (CR) rate (per 2006 International Working Group criteria) and overall survival (OS). RESULTS: At final analysis, 539 patients were randomly assigned to Magro/Aza (n = 268) or Placebo/Aza (n = 271) arms. Baseline characteristics were generally well balanced between treatment arms. In the Magro/Aza versus Placebo/Aza arms, the CR rate was 21.3% versus 23.6% (odds ratio, 0.876 [95% CI, 0.585 to 1.312]; P = .5218), and median OS was 15.9 versus 18.6 months (hazard ratio, 1.203 [95% CI, 0.947 to 1.528]; P = .1299). Magro/Aza had a higher incidence of grade ≥3 adverse events (AEs; 92.8% v 79.2%), AE-associated study drug discontinuations (24.0% v 12.1%), serious AEs (71.9% v 51.5%), and fatal AEs (15.2% v 9.8%) versus Placebo/Aza. CONCLUSION: ENHANCE did not meet the primary end points of CR rate and OS, and showed more frequent severe AEs in patients treated in the Magro/Aza arm.

Supplementary Figure 2. Trispecific CAR T Cell Persistence by gag gene PCR (single dose infusion versus split dose infusion).

Supplementary Figure 4. Immunophenotypic and functional characteristics CD8+ CAR + T cells and CD4+ CAR + T cells in post-CAR T infusion PBMCs at Day 7.

Supplementary Figure 1. Trial Schema.

Supplementary Table 2. Toxicity and other clinical outcomes.

Supplementary Figure 6. Trispecific CAR + T cell Gating Strategy for spectral flow cytometry.

Supplementary Figure 3. Statistical Analysis (Area Under the Curve) Trispecific CAR T Cell Persistence by PCR Data.

Supplementary Figure 5: Immunophenotypic and functional characteristics CD8+ CAR + T cells and CD4+ CAR + T cells in Post-CAR T PBMCs at Day 14.