Contributions
Abstract: EP547
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
CD19 CAR T cells induce complete remissions in ≥40% of heavily pretreated patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). However, a significant proportion of patients shows refractory disease or relapses early after therapy. Thus, the identification of predictors of durable responses is of interest not only to guide patient selection, but also to investigate resistance mechanisms and improve efficacy.
Aims
We assessed the predictive value of clinical and laboratory parameters for progression-free survival (PFS) of r/r DLBCL patients treated with CD19 CAR T cells.
Methods
Patient and disease characteristics, toxicities, PET/CT response and survival of r/r DLBCL patients treated with Axicabtagene Ciloleucel or Tisagenlecleucel at our institution were retrospectively assessed. We assessed pre-defined patient and lymphoma characteristics known to confer adverse outcomes in DLBCL for their association with PFS by univariable log-rank tests, as well as multivariable forward stepwise Cox regression analyses. Analysed Characteristics encompassed age, refractoriness to first-line therapy and no. of prior therapy lines. Additionally, tumor volume, presence of bulky disease (>10cm), presence of extranodal disease (END), Ann Arbor stage, IPI, LDH and ECOG, all assessed at time of lymphodepletion, were included in the analysis.
Results
As of November 2020, 41 DLBCL patients have been leukapheresed, and 35 patients have been transfused. Median age was 60 years (range 19-82). ECOG was 0-1 in 23, and 2-3 in twelve patients at time of CAR T-cell transfusion. Only 3 of the 35 transfused patients (9%) would have met the inclusion criteria of the pivotal clinical trials at all timepoints (enrolment, apheresis, and time of lymphodepletion).
CRS occurred in 32/35 patients (80% CRS °1-2, 11% °3). 16 patients (45%) experienced ICANS (29% °1-2, 14% °3-4, and 3% °5). Median follow-up was 4.4 months. Response assessment after three months was available for 34/35 patients. Objective response rate was 53%, with complete remission in 15 (44%) and partial remission in three patients (9%).
In univariable analyses, apart from primary refractory disease (p=0.79), all pre-selected markers were suggestive to be associated with PFS (p=0.002-0.061). We therefore included all variables that were indicative of shorter PFS (p<0.1) in univariable analyses in multivariable AIC-based forward stepwise Cox regression analyses. In the resulting model, presence of END was associated with inferior PFS (Hazard ratio [HR] 11.3, p=0.02), adjusted for prior therapy lines (HR 1.3, p=0.06) and ECOG>1 (HR 2.3, p=0.12). Other variables did not improve the prognostic validity of the model. The relevance of END for PFS was confirmed in additional two-variable Cox regression analyses, each adjusted for one marker from the multivariable model.
Conclusion
We provide real-world evidence that CD19 CAR T cells induce remissions in a substantial proportion of r/r DLBCL patients, although only 9% of our patients would have met the inclusion criteria of the pivotal trials. In the patient cohort, extranodal disease at transfusion was associated with significantly shorter PFS both in uni- and multivariable analyses. To understand and overcome this potential resistance mechanism, we have set up a comprehensive immunomonitoring program with specific focus on the lymphoma microenvironment in nodal and extranodal sites.
Keyword(s): CAR-T, DLBCL
Abstract: EP547
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
CD19 CAR T cells induce complete remissions in ≥40% of heavily pretreated patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). However, a significant proportion of patients shows refractory disease or relapses early after therapy. Thus, the identification of predictors of durable responses is of interest not only to guide patient selection, but also to investigate resistance mechanisms and improve efficacy.
Aims
We assessed the predictive value of clinical and laboratory parameters for progression-free survival (PFS) of r/r DLBCL patients treated with CD19 CAR T cells.
Methods
Patient and disease characteristics, toxicities, PET/CT response and survival of r/r DLBCL patients treated with Axicabtagene Ciloleucel or Tisagenlecleucel at our institution were retrospectively assessed. We assessed pre-defined patient and lymphoma characteristics known to confer adverse outcomes in DLBCL for their association with PFS by univariable log-rank tests, as well as multivariable forward stepwise Cox regression analyses. Analysed Characteristics encompassed age, refractoriness to first-line therapy and no. of prior therapy lines. Additionally, tumor volume, presence of bulky disease (>10cm), presence of extranodal disease (END), Ann Arbor stage, IPI, LDH and ECOG, all assessed at time of lymphodepletion, were included in the analysis.
Results
As of November 2020, 41 DLBCL patients have been leukapheresed, and 35 patients have been transfused. Median age was 60 years (range 19-82). ECOG was 0-1 in 23, and 2-3 in twelve patients at time of CAR T-cell transfusion. Only 3 of the 35 transfused patients (9%) would have met the inclusion criteria of the pivotal clinical trials at all timepoints (enrolment, apheresis, and time of lymphodepletion).
CRS occurred in 32/35 patients (80% CRS °1-2, 11% °3). 16 patients (45%) experienced ICANS (29% °1-2, 14% °3-4, and 3% °5). Median follow-up was 4.4 months. Response assessment after three months was available for 34/35 patients. Objective response rate was 53%, with complete remission in 15 (44%) and partial remission in three patients (9%).
In univariable analyses, apart from primary refractory disease (p=0.79), all pre-selected markers were suggestive to be associated with PFS (p=0.002-0.061). We therefore included all variables that were indicative of shorter PFS (p<0.1) in univariable analyses in multivariable AIC-based forward stepwise Cox regression analyses. In the resulting model, presence of END was associated with inferior PFS (Hazard ratio [HR] 11.3, p=0.02), adjusted for prior therapy lines (HR 1.3, p=0.06) and ECOG>1 (HR 2.3, p=0.12). Other variables did not improve the prognostic validity of the model. The relevance of END for PFS was confirmed in additional two-variable Cox regression analyses, each adjusted for one marker from the multivariable model.
Conclusion
We provide real-world evidence that CD19 CAR T cells induce remissions in a substantial proportion of r/r DLBCL patients, although only 9% of our patients would have met the inclusion criteria of the pivotal trials. In the patient cohort, extranodal disease at transfusion was associated with significantly shorter PFS both in uni- and multivariable analyses. To understand and overcome this potential resistance mechanism, we have set up a comprehensive immunomonitoring program with specific focus on the lymphoma microenvironment in nodal and extranodal sites.
Keyword(s): CAR-T, DLBCL