Patients were followed for a median of 12.8 (IQR 6.4–16.0) months after CAR-T infusion. Median OS was not reached. Six-months and 1-year survival rates were 70.7% and 52.4%, respectively.
Prediction of survival and toxicity prior to CAR-T infusion
In a univariate Cox regression analysis shown in Table 2, several PET and clinical parameters were found to be significantly predictive of OS and PFS prior to infusion of CAR-T. Patients with TD-SUVmax > 17.1 and patients with TT-SUVmax > 12.1 had significantly shorter OS and PFS (see Fig. 1). Higher TT-TMTV and higher TT-TLG were also identified as risk factors for poor OS. Patients with elevated LDH and ECOG performance score > 1 had significantly shorter OS and PFS.
In a multivariate Cox regression analysis (Table 3) for OS that included age, sex, LDH, ECOG score, TD-SUVmax, TT-SUVmax, TT-TMTV and TT-TLG as dichotomous variables, three independent prognostic factor were identified: TD-SUVmax > 17.1 (HR 10.3; 95% CI, 2.2–47.7; Pv < 0.01), Serum LDH > 450 U/l (HR 7.7; 95% CI, 1.9–32.0; Pv < 0.01) and ECOG score > 1 (HR 5.5; 95% CI, 1.1–31.0; Pv = 0.04).
Based on this multivariate model, we assigned a score between 0 and 3 to each of the study patients, based on the number of the independent risk factors that they meet (TD-SUVmax, LDH level and ECOG performance). On Fig. 2, the OS curves of patients with different scores is shown. Patients in our data that met all of the three criteria (assigned a score of 3) had median OS of 2.6 (95% CI, 1.1-4.0) months.
Response to bridging therapy as evaluated on the TT scan was not significantly associated with PFS and OS using both the Deauville five-point scale and ΔSUVmax methods. Only the minority of patients met the favorable response criteria: 7 patients (16.7%) had Deauville score ≤ 3, and 2 patients (6.7%) had ΔSUVmax > 66% on their TT scan.
Among the patients that underwent PET-CT prior to CART transfusion, the post-therapy incidences of any-grade CRS, grade 3–4 CRS and ICANS were 76.2% (32/42 patients), 11.9% (5/42 patients) and 21.4% (9/42 patients), respectively. No statistically significant association was found between TD or TT PET variables and CRS or ICANS in this cohort.
Imaging interpretation of post-CAR-T PET-CT
Response to CAR-T therapy as evaluated on the M1-PET-CT scan was significantly associated with OS using the Deauville five-point scale. While those with Deauville score > 3 had median survival of 7.9 (95% CI, 3.8–12.0) months, median survival of those with Deauville score ≤ 3 was not reached (Pv < 0.01). While the 1-year OS for patients with favorable response was 94%, it was 20% for those with poor response based on the Deauville scale (Fig. 3A).
Using the ΔSUVmax method, response assessment to CAR-T therapy on the M1-PET-CT scan was not associated with OS when the reference baseline SUVmax was obtained from the TT-PET scan (Pv = 0.38) but was significantly associated with OS when the TD-SUVmax was used as the baseline SUVmax (Pv = 0.02). Using the ΔSUVmax method with TD-SUVmax as reference, the median survival of those who met the favorable criterion was not reached, and those categorized with poor response had median survival of 8.2 (95% CI, 1.3–15.1) months (Pv = 0.02) (Fig. 3B, 3C).
In the group of patients who had a PET-CT scan three months post-CAR-T infusion and were not given any other anti-lymphoma therapy since the CAR-T infusion, response to therapy on the M3 scan was significantly associated with OS using the Deauville five-point scale (Pv < 0.01). The ΔSUVmax method could significantly predict OS when the baseline SUVmax was obtained from the TD or TT scan (Pv = 0.02 for both, Fig. 4) but not from M1 scan (Pv = 0.25).
In multivariate analysis that included the response assessment criteria that were significantly associated with OS on M1 and M3 PET-CT scans, Deauville score > 3 on M1-PET was the only factor significantly associated with OS (HR 7.2; 95% CI, 1.5–34.6; Pv = 0.01).