Contributions
Abstract: EP729
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Relapsed/refractory (R/R) diffuse large B-cell (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) have a very poor prognosis with standard chemotherapy. The recently approved axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are anti-CD19 chimeric antigen receptor T cells (CAR-T) that proved very effective in clinical trials and real-life setting. The Italian Society of Hematology (SIE) is conducting a prospective observational trial to evaluate safety and efficacy in patients (pts) treated with axi-cel and tisa-cel.
Aims
of the study are: 1. to register all DLBCL and PMBCL pts candidate to CAR-T in the Italian authorized centers; 2. to evaluate the intention to treat overall response rate (ORR, complete [CR] and partial response [PR]); 3. to evaluate duration of response (DOR), progression free survival (PFS) and overall survival (OS); 4. to evaluate safety in terms of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and long-term cytopenia; 5. to evaluate different CAR-T products.
Methods
SIE designed a multicenter prospective observational study, approved by ethics committee of all centers. All pts treated since March 2019 to January 2021, were included into this national study.
Results
126 pts were leukapheresed. Thirteen pts showed a rapid progression (10) or fatal infection (3) during the manufacturing and were not infused. The clinical characteristics of the 113 infused pts were: median age 53 years (19-70), male 64 (57%), stage III/IV 77 (68%), bulky disease 51 (45%); median number of prior lines was 3 (2-7); 33 patients (29%) failed a previous autologous stem cell transplantation and 81 (72%) were primary refractory. For histologies, 59 (52%) were DLBCL, 18 (16%) high-grade B-cell (HGBCL), 23 (20%) PMBCL, 13 (12%) transformed Follicular (tFL). Median lymphocyte count at the apheresis was 810/mm3 (250-8900). Bridging therapy was delivered to 97 pts (86%). All pts received Flu-Cy lymphodepletion. Fifty-nine (52%) received axi-cel and 54 (48%) tisa-cel. Median follow-up time for infused pts was 6.9 months (IQR: 3.13-11.78). At 30-days after the infusion, all the 113 infused pts were evaluable for response: 45 (40%) CR, 35 (31%) PR, with and encouraging ORR of 71%. For the evaluable pts, DOR was 73% (95%CI:62-85) at 6-months and 58% (95%CI:44-77) at 12-months. In the whole series, 6 and 12-months PFS were 54% (95% CI:45-65) and 46% (95%CI:35-59); 6 and 12-months OS were 80% (95%CI:71-88) and 75% (95%CI:65-86), respectively. With the limitation of small number, 6-months PFS were 48% for DLBCL, 62% for HGBCL, 66% for PMBCL and 59% for tFL; 6-months OS by histotype were 78% for DLBCL, 80% for HGBCL, 80% for PMBCL and 92% for tFL. No differences between axi-cel and tisa-cel were reported in terms of OS and PFS. All grade CRS was observed in 87 (77%) of 113 pts, but only 6 (5%) were grade 3 or 4; ICANS was recorded in 31 (27%) patients, but only 11 (10%) were grade 3 or 4. Sixty-one (54%) pts received tocilizumab and 38 (34%) steroids. Cytopenia beyond 30 days was reported in 30 (27%) pts and 27 of them (24%) experienced viral or bacterial infections. No toxic deaths were recorded.
Conclusion
In the real-life, axi-cel and tisa-cel showed an ORR similar to those of the registrative trials, even if almost all pts underwent bridging therapy. The response rate is similar across histotypes and between products. CAR-T toxicity is manageable, relapse beyond 6 months is a rare event. Cytopenias as well as infections are an emerging problem in real-life setting.
Keyword(s): B cell lymphoma, CAR-T, Diffuse large B cell lymphoma, Relapsed lymphoma
Abstract: EP729
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Relapsed/refractory (R/R) diffuse large B-cell (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) have a very poor prognosis with standard chemotherapy. The recently approved axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are anti-CD19 chimeric antigen receptor T cells (CAR-T) that proved very effective in clinical trials and real-life setting. The Italian Society of Hematology (SIE) is conducting a prospective observational trial to evaluate safety and efficacy in patients (pts) treated with axi-cel and tisa-cel.
Aims
of the study are: 1. to register all DLBCL and PMBCL pts candidate to CAR-T in the Italian authorized centers; 2. to evaluate the intention to treat overall response rate (ORR, complete [CR] and partial response [PR]); 3. to evaluate duration of response (DOR), progression free survival (PFS) and overall survival (OS); 4. to evaluate safety in terms of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and long-term cytopenia; 5. to evaluate different CAR-T products.
Methods
SIE designed a multicenter prospective observational study, approved by ethics committee of all centers. All pts treated since March 2019 to January 2021, were included into this national study.
Results
126 pts were leukapheresed. Thirteen pts showed a rapid progression (10) or fatal infection (3) during the manufacturing and were not infused. The clinical characteristics of the 113 infused pts were: median age 53 years (19-70), male 64 (57%), stage III/IV 77 (68%), bulky disease 51 (45%); median number of prior lines was 3 (2-7); 33 patients (29%) failed a previous autologous stem cell transplantation and 81 (72%) were primary refractory. For histologies, 59 (52%) were DLBCL, 18 (16%) high-grade B-cell (HGBCL), 23 (20%) PMBCL, 13 (12%) transformed Follicular (tFL). Median lymphocyte count at the apheresis was 810/mm3 (250-8900). Bridging therapy was delivered to 97 pts (86%). All pts received Flu-Cy lymphodepletion. Fifty-nine (52%) received axi-cel and 54 (48%) tisa-cel. Median follow-up time for infused pts was 6.9 months (IQR: 3.13-11.78). At 30-days after the infusion, all the 113 infused pts were evaluable for response: 45 (40%) CR, 35 (31%) PR, with and encouraging ORR of 71%. For the evaluable pts, DOR was 73% (95%CI:62-85) at 6-months and 58% (95%CI:44-77) at 12-months. In the whole series, 6 and 12-months PFS were 54% (95% CI:45-65) and 46% (95%CI:35-59); 6 and 12-months OS were 80% (95%CI:71-88) and 75% (95%CI:65-86), respectively. With the limitation of small number, 6-months PFS were 48% for DLBCL, 62% for HGBCL, 66% for PMBCL and 59% for tFL; 6-months OS by histotype were 78% for DLBCL, 80% for HGBCL, 80% for PMBCL and 92% for tFL. No differences between axi-cel and tisa-cel were reported in terms of OS and PFS. All grade CRS was observed in 87 (77%) of 113 pts, but only 6 (5%) were grade 3 or 4; ICANS was recorded in 31 (27%) patients, but only 11 (10%) were grade 3 or 4. Sixty-one (54%) pts received tocilizumab and 38 (34%) steroids. Cytopenia beyond 30 days was reported in 30 (27%) pts and 27 of them (24%) experienced viral or bacterial infections. No toxic deaths were recorded.
Conclusion
In the real-life, axi-cel and tisa-cel showed an ORR similar to those of the registrative trials, even if almost all pts underwent bridging therapy. The response rate is similar across histotypes and between products. CAR-T toxicity is manageable, relapse beyond 6 months is a rare event. Cytopenias as well as infections are an emerging problem in real-life setting.
Keyword(s): B cell lymphoma, CAR-T, Diffuse large B cell lymphoma, Relapsed lymphoma