Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).

2021 Update on Diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management

“…In a retrospective study of commercial anti‐CD19 CAR‐T in patients with RR DLBCL, 49% of relapses after CAR T‐cell treatment occur within the first month. Risk factors for early progression were ≥ two extranodal sites, increased CRP, and high total metabolic tumor volume at the time of treatment 70 . The association between disease burden and early relapse raises the possibility that CAR T cells may be more effective and safer if used as consolidation and/or earlier on in the disease course since CAR T cell efficacy relies on the fitness of the endogenous T cell repertoire, which can be compromised by extensive prior therapy and high disease burden.…”

LncRNA SNHG8 Promotes Proliferation and Inhibits Apoptosis of Diffuse Large B-Cell Lymphoma via Sponging miR-335-5p

“…Usually, patients with stages I or II of DCBCL are treated with chemotherapy in combination with a comprehensive treatment, and those with stages III or IV of DLBCL are mainly treated with chemotherapy ( 20 ). The common chemotherapeutic drugs for DLBCL include methyl-benzylhydrazine, cyclophosphamide, nitrogen mustard, and other alkylating agents ( 21 ). The comprehensive treatment is to control distant metastasis of the tumor.…”

Case Report: Combined Intravenous Infusion and Local Injection of CAR-T Cells Induced Remission in a Relapsed Diffuse Large B-Cell Lymphoma Patient

“…Consistent with the guideline, the patient was enrolled in CAR-T cell therapy's clinical trial after relapse from R-CHOP. In CAR-T cells treated lymphoma patients, extranodal lesions generally correlate with poor response and poor outcome (6)(7)(8). The reason may be the relatively less blood supply and the barrier effect of extranodal lesions leading to a low number of CAR-T cells in local lesions.…”

“…Recently, the impact of extranodal lesions on CAR-T cell therapy has been evaluated. Extranodal lesions present a poor response than lymph nodes in R/R Hodgkin's lymphoma patients (6), and extranodal lesions are a poor indicator of early progression in R/R DLBCL patients (7). What's more, soft tissue infiltration correlated with adverse prognosis in R/R DLBLC patients (8).…”