CAR T-cell therapy for primary refractory disease or relapse within 1 year (or relapse after autologous SCT)

A prospective randomized trial included 359 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy axicabtagene ciloleucel (axi-cel) with only bridging steroids or second-line chemoimmunotherapy (usually R-ICE [rituximab, ifosfamide, etoposide, and carboplatin] or R-DHAP [rituximab, dexamethasone, high-dose cytarabine, and cisplatin]) followed by autologous SCT.[7,8]

A prospective randomized trial included 359 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy axicabtagene ciloleucel (axi-cel) with only bridging steroids or second-line chemoimmunotherapy (usually R-ICE [rituximab, ifosfamide, etoposide, and carboplatin] or R-DHAP [rituximab, dexamethasone, high-dose cytarabine, and cisplatin]) followed by autologous SCT.[7,8]

With a median follow-up of 47.2 months, the median OS was not reached in the axi-cel cohort and was 31.1 months in the chemoimmunotherapy cohort. The estimated 4-year OS rate was 54.6% for patients who received axi-cel and 46.0% for patients who received chemoimmunotherapy (hazard ratio [HR]death, 0.73; 95% confidence interval [CI], 0.54–0.98; P = .03).[8][Level of evidence A1]

A prospective randomized trial included 359 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy axicabtagene ciloleucel (axi-cel) with only bridging steroids or second-line chemoimmunotherapy (usually R-ICE [rituximab, ifosfamide, etoposide, and carboplatin] or R-DHAP [rituximab, dexamethasone, high-dose cytarabine, and cisplatin]) followed by autologous SCT.[7,8]

The median investigator-assessed PFS was 14.7 months in the axi-cel cohort and 3.7 months in the chemotherapy cohort (HR, 0.51; 95% CI, 0.38–0.67).

A prospective randomized trial included 359 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy axicabtagene ciloleucel (axi-cel) with only bridging steroids or second-line chemoimmunotherapy (usually R-ICE [rituximab, ifosfamide, etoposide, and carboplatin] or R-DHAP [rituximab, dexamethasone, high-dose cytarabine, and cisplatin]) followed by autologous SCT.[7,8]

In the chemoimmunotherapy arm, 64% patients never received autologous SCT during the study because of inadequate response, progression, or death.[7]

A prospective randomized trial included 359 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy axicabtagene ciloleucel (axi-cel) with only bridging steroids or second-line chemoimmunotherapy (usually R-ICE [rituximab, ifosfamide, etoposide, and carboplatin] or R-DHAP [rituximab, dexamethasone, high-dose cytarabine, and cisplatin]) followed by autologous SCT.[7,8]

Clinically meaningful and statistically significant differences in quality of life were obtained in the CAR T-cell arm at day 100 and day 150, compared with the standard of care.[7][Level of evidence A2]

A prospective randomized trial included 359 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy axicabtagene ciloleucel (axi-cel) with only bridging steroids or second-line chemoimmunotherapy (usually R-ICE [rituximab, ifosfamide, etoposide, and carboplatin] or R-DHAP [rituximab, dexamethasone, high-dose cytarabine, and cisplatin]) followed by autologous SCT.[7,8]

Grade 3 or 4 cytokine release syndrome occurred in 6% of patients, and grade 3 or 4 neurotoxicity occurred in 21% of patients.

A prospective randomized trial included 184 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy lisocabtagene maraleucel (liso-cel), with 63% of patients receiving bridging therapy or second-line chemoimmunotherapy followed by autologous SCT.[9]

A prospective randomized trial included 184 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy lisocabtagene maraleucel (liso-cel), with 63% of patients receiving bridging therapy or second-line chemoimmunotherapy followed by autologous SCT.[9]

With a median follow-up of 17.5 months, the median PFS was not reached for patients who received liso-cel and was 6.2 months for patients who received chemoimmunotherapy followed by autologous SCT (HR, 0.40; P < .0001).[9][Level of evidence B1]

A prospective randomized trial included 184 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy lisocabtagene maraleucel (liso-cel), with 63% of patients receiving bridging therapy or second-line chemoimmunotherapy followed by autologous SCT.[9]

On the chemoimmunotherapy arm of the study, 53% of patients never received autologous SCT because of inadequate response, progression, or death.[9]

A prospective randomized trial included 184 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy lisocabtagene maraleucel (liso-cel), with 63% of patients receiving bridging therapy or second-line chemoimmunotherapy followed by autologous SCT.[9]

Grade 3 cytokine release syndrome occurred in 1% of patients, and grade 3 neurotoxicity occurred in 4% of patients. There were no grade 4 or 5 occurrences.

A prospective randomized trial included 322 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy tisagenlecleucel, with most patients receiving bridging therapy to achieve response, or second-line chemoimmunotherapy followed by autologous SCT.[10]

A prospective randomized trial included 322 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy tisagenlecleucel, with most patients receiving bridging therapy to achieve response, or second-line chemoimmunotherapy followed by autologous SCT.[10]

There was no difference in event-free survival (EFS) for patients in either arm (HR, 1.07; 95% CI, 0.82–1.40; P = .69).[10][Level of evidence B1]

A prospective randomized trial included 322 patients with primary refractory disease or relapse within 12 months of initial R-CHOP chemotherapy. Patients received the CAR T-cell therapy tisagenlecleucel, with most patients receiving bridging therapy to achieve response, or second-line chemoimmunotherapy followed by autologous SCT.[10]

In the CAR T-cell therapy arm, 48% of patients received two or more cycles of chemoimmunotherapy as part of bridging therapy. This approach to bridging therapy may have led to an unacceptable number of cases of progressive disease.

For patients with high-risk relapsing DLBCL with primary refractory disease or relapse within 12 months of R-CHOP-based chemotherapy, axi-cel and liso-cel are superior induction regimens, compared with chemoimmunotherapy with regimens like R-ICE, R-DHAP, and R-GDP (rituximab, gemcitabine, dexamethasone, and cisplatin).

The interval until patients receive CAR T cells must be minimized, optimally by using only steroids, eliminating bridging chemoimmunotherapy, and infusing the CAR T-cell product as quickly as possible.

The preference for CAR T-cell therapy over chemoimmunotherapy followed by autologous SCT does not apply to patients who relapse more than 12 months after R-CHOP therapy.

The American Society of Clinical Oncology (ASCO) has compiled guidelines for the management of adverse events in patients treated with CAR T-cell therapy.[11]

Worse outcomes were reported when apheresis for CAR T-cell therapy occurred just after bendamustine therapy. In a retrospective multicenter review of 439 patients who were infused with CD-19–targeted CAR T cells, 80 patients had received prior bendamustine. With a median follow-up of 20.6 months after CAR T-cell infusion, the patients who had received prior bendamustine had a lower overall response rate (53% vs. 72%, P < .01), worse median PFS (3.1 vs. 6.2 months, P = .04), and worse median OS (4.6 vs. 23.5 months, P < .01).[12][Level of evidence C1]