ARRS 2022 Abstracts


E1021. Change in Metabolic Tumor Volume After Prior Systemic Therapy Predicts CAR T-Cell Therapy Outcomes for Aggressive B-Cell Lymphomas
  1. Hwan Lee; University of Pennsylvania Perelman School of Medicine
  2. Alexandra Nader; University of Pennsylvania Perelman School of Medicine
  3. Mark Sellmyer; University of Pennsylvania Perelman School of Medicine
  4. Elise Chong; University of Pennsylvania Perelman School of Medicine
Anti-CD19 chimeric antigen receptor modified T-cells (CAR-T) have expanded the available treatment options for patients with relapsed/refractory (R/R) aggressive large B-cell lymphomas (B-NHL), but a majority of patients fail to achieve long-term remission. We examined whether quantitative assessment of response using 18F-fluorodeoxyglucose (FDG) PET/CT after the most recent systemic therapy is associated with CAR-T outcomes.

Materials and Methods:
We retrospectively analyzed the medical records of 50 patients with R/R B-NHL treated with CAR-T from April 2018 to August 2020. Two 18F-FDG PET/CT scans immediately preceding CAR-T therapy were reviewed for quantitative assessment of relative change in metabolic tumor volume (dMTV) from the T-2 scan (PET/CT before systemic therapy) to T-1 scan (PET/CT after systemic therapy and before CAR-T), expressed as percentages bounded from -100% to +100%. Univariate and multivariate Cox regression analysis was performed to identify predictors of progression-free survival (PFS) and overall survival (OS). Post-hoc Kaplan-Meier survival analysis was performed based on the optimal dMTV cutoff.

The study population included 23 women (46%) and the median age was 61 (range 29-82). Most patients (95%) had ECOG performance status of 0-1, with a median number of 3 prior therapies (range 1-11). The CAR-T product was tisagenlecleucel in 68% of patients and axicabtagene ciloleucel in 32%. Serum lactate dehydrogenase (LDH) was elevated in 28% of patients at CAR-T infusion. Lymphodepleting therapy was bendamustine in 66% and cyclophosphamide+fludarabine in 34%. Bridging therapy was utilized in 52%. 10% of patients had double-hit lymphoma. Median time from T-2 to T-1 PET/CT was 63 days (range: 21-355), and 47 days (range: 6-155) from T-1 scan to CAR-T infusion. Median PFS and OS were 4.5 and 26.2 months, respectively. While the MTV decreased in general prior to CAR-T (median dMTV: -26%, range: ±100%), increased MTV was associated with worse outcomes. On univariate regression, increased MTV was associated with shorter PFS (p=0.016, HR=1.8), whereas age (p=0.77), gender (p=0.84), elevated LDH (p=0.28), use of bridging therapy (p=0.44), double-hit translocations (p=0.92), and three or more prior therapies (p=0.41) were not statistically significant. On multivariate regression, only dMTV had significant effect on PFS (p=0.006, HR=2.1). Similarly, increased MTV pre-CAR-T was associated with shorter OS (p=0.015, HR=2.5 on multivariate analysis). On post-hoc Kaplan-Meier analysis, over 25% increase in MTV was associated with shorter PFS (median 3.1 vs 14.4 months, p=0.004 on log-rank test) and OS (median 15.8 vs. >36.9 months, p=0.005 on log-rank test).

In R/R B-NHL patients receiving CAR-T therapy, quantitative change in MTV on 18F-FDG PET/CT in response to prior systemic therapy was most strongly associated with survival. While the observed general decrease in MTV between the two prior scans was consistent with systemic therapy effects, increasing MTV despite systemic therapy was strongly correlated with poor outcomes following subsequent CAR-T therapy.