Prognostic factors for cellular therapies ‐ CART and allogeneic SCT ‐ in relapsed /refractory large B cell lymphoma (LBCL)

Introduction: Allogeneic stem cell transplantation (alloSCT) was the only curative option for younger patients (pts) with relapsed/ refractory (r/ r) LBCL (DLBCL, tFL, PMBCL). Anti-CD19 CAR T-cells (CART) entered the clinical arena around 5 years ago now being considered standard of care for such patients. As >50% of LBCL pts progress or relapse after CART treatment we were interested in identifying prognostic factors for both modalities and their relative role in the treatment of advanced r/r LBCL. Methods: Pts registered with the EBMT database from 1/2016 to 5/2021 having received either a first alloSCT or commercially available CART therapy (Yescarta® or Kymriah ®) as ≥3rd therapy of LBCL were analyzed. To correct for imbalances in patient characteristics we did propensity score analyses considering only pts with complete information on IPI including LDH at the time of cell therapy. We performed multivariate analyses in patients with either low- or high-risk r/r LBCL according to LDH level at cell therapy in pts treated with alloSCT or CART. Results: We identified 515 pts with full information on IPI at cell therapy (212 alloSCT and 303 CART). Patient groups differed significantly in median age, IPI score, and disease status at cell therapy. Median follow up was 46.3 months after alloSCT and 22.1 months after CART treatment. In univariate analysis, type of cell therapy, disease status, and IPI at cell therapy had a significant impact on OS. Amongst IPI risk factors LDH, performance status, and number of extranodal sites had a significant impact on OS, PFS an RI. At 24 months, OS was 41% after allo SCT and 49% after CART. In a propensity score analysis using all IPI factors as covariates, CART was superior to alloSCT in terms of OS (HR 0.62, 95% CI: 45–0.84, p = 0.0193) but not PFS, RI or NRM. In multivariate analysis patients with IPI (o-2) low risk at cell therapy show better OS (HR 0.81, 95% CI 0.59–1.1, p < 0.0001) and PFS (HR 0.62, CI: 0.46–0.83, p = 0.00145), comparable RI and lower NRM (HR 0.21 CI: 0.11–0.42, p = 0.00001) with CART compared to allo SCT. In IPI (3–5) high-risk patients, CART showed significantly higher RI (HR 1.45, CI: 1.03–2.04, p = 0.03549) but lower NRM (HR 0.21, CI: 0.11–0.42), p = 0.00001) compared to allo SCT. OS and PFS did not significantly differ. Refractory disease was an independent adverse prognostic factor for OS (HR 1.74, CI: 1.3–2.33, p = 0.0002), PFS (HR 1.61 CI: 1.23–2.1, p = 0.0006) and RI (HR 1.79 CI: 1.29–2.49, p = 0.0006) but not for NRM. Results at 2 years are given in Table 1. Conclusion: IPI assessed at cell therapy is of prognostic impact for both CART and allo SCT. Overall, pts given CART for ≥3rd line treatment of DLBCL showed better OS than pts treated with alloSCT. In patients with high intermediate/high IPI results of CART must be improved and allogeneic SCT remains a valuable treatment strategy due to its high anti-lymphoma activity. Keyword: Cellular therapies Conflicts of interests pertinent to the abstract. B. Glass Consultant or advisory role: Kite, BMS, Novartis, Milteneyi, Roche, Janssen, Jazz, Abbvie Honoraria: Kite, BMS, Novartis, Milteneyi, Roche, Janssen, Jazz, Abbvie Research funding: Roche, Riemser A. Sureda Consultant or advisory role: Takeda, MSD, BMS, Novartis, Janssen, Roche, Sanofi, Gilead P. Dreger Consultant or advisory role: Kite, Novartis P. Corradini Honoraria: Abbvie, Amgen, Celgene, Giled, Incyte, Janssen, Takeda, R. Ram Honoraria: Novartis, Gilead, Takeda, BMS G. Wulf Consultant or advisory role: Gilead, Novartis A. M. García-Sancho Consultant or advisory role: Roche, BMS, Kyowa Kirin, Clinigen, Eusa Pharma, Novartis, Kite Gilead, Servier, Incyte, Lilly, Takeda, ADC Therapeutics America, Miltenyi, Kern M. Stelljes Consultant or advisory role: Medac, Pfizer, Jazz, Novartis, MSD, Amgen, BMS, Kite D. Blaise Consultant or advisory role: Jazz E. Forcade Consultant or advisory role: Gilead, Jazz, Novartis, GSK, Sanofi, MSD I. Hilgendorf Consultant or advisory role: Novartis, Abbvie J. A. Perez-Simon Consultant or advisory role: Novartis, Janssen, Gilead, Jazz, Alexion, Abbvie, Pfizer W. Bethge Consultant or advisory role: Gilead, Novartis, Miltenyi, Janssen, Celgene N. Schmitz Consultant or advisory role: Allogene Stock ownership: BMS Honoraria: Allogene Research funding: Janssen, Roche Educational grants: Allogene, Milteneyi