During 2022, the FDA approved 2 chimeric antigen receptor (CAR) T-cell therapies for use in second-line treatment, offering new treatment choices but raising the question: What options remain once a patient relapses after CAR T?
In abstracts featured at the 64th American Society of Hematology Annual Meeting and Exposition, investigators detailed patient and financial outcomes associated with chimeric antigen receptor (CAR) T-cell therapies vs standard of care (SOC) for treatment of large B-cell lymphoma (LBCL). During 2022, the FDA approved 2 CAR T-cell therapies for use in second-line treatment,1,2 offering new treatment choices but raising the question: What options remain once a patient relapses after CAR T?
Long-term liso-cel data. Jeremy Abramson, MD, director of the lymphoma program at Massachusetts General Hospital Cancer Center in Boston, presented updated outcomes from the TRANSFORM study (NCT03575351), which aimed to compare the efficacy and safety of the CAR T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi) vs SOC as second-line therapy in patients with relapsed or refractory LBCL.3 Both liso-cel and the SOC of salvage immunochemotherapy were followed by high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) in those responding to treatment. The multicenter phase 3 study included 184 patients, with 92 randomly assigned to each arm.
After a median follow-up of 17.5 months, the primary end point of event-free survival (EFS) was not reached (NR) for the liso-cel arm (95 CI, NR-9.5 months) vs a median (95% CI) of 2.4 (2.2-4.9) months for the SOC arm. Investigators also observed statistically significant results favoring liso-cel for the complete response (CR) rate (74% vs 43%, respectively; P<.0001) and progression-free survival (PFS) (median [95% CI], NR [12.6-NR] vs 6.2 [4.3-8.6] months; P <.0001). These updated findings confirmed results presented at the American Society of Hematology Annual Meeting and Exposition in December 2021 in Atlanta, Georgia, after a median follow-up of 6.2 months.3
Median overall survival was also longer for those in the liso-cel arm, but the difference vs SOC was not statistically significant (NR vs 29.9 months; P = .0987).3
These results showed deepened responses among some patients who had a partial response (PR) as of an interim analysis, as outcomes improved to a CR in 6 of 18 patients in the liso-cel arm and 3 of 8 in the SOC arm.3
“In TRANSFORM, liso-cel resulted in statistically significant and clinically meaningful improvements in EFS, CR rate, and PFS,” the abstract concluded. “These data reinforce liso-cel as a [second-line] treatment in [patients] with primary refractory or early relapsed LBCL.”
The FDA approved liso-cel for second-line treatment on June 24, 2022.2
After axi-cel, then what? Another abstract examined how well the CAR T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) vs SOC set the stage for later antilymphoma therapies among patients with LBCL in the phase 3 ZUMA-7 trial (NCT03391466).4 As the authors explained, axi-cel is approved for treatment of relapsed/refractory LBCL after first-line therapy, but little is currently known about optimal management after a second line of therapy. (The FDA approved axi-cel for use in second-line treatment April 1, 2022.1)
Of the 84 patients in the axi-cel arm of the ZUMA-7 trial who required subsequent third-line therapy, 60 received chemotherapy and 8 received cellular immunotherapy, which was axi-cel retreatment for those who initially responded to axi-cel. Those who received chemotherapy had a median (95% CI) PFS of 1.7 (1.4-2.0) months and an OS of 8.1 (5.8-11.5) months; the objective response rate (ORR) was 25%, and the CR rate was 13%. Specifically, among those who had shown an initial response to second-line axi-cel, the ORR was 32% and the CR rate was 18%.4
In the 8 patients who received cellular immunotherapy after axi-cel, the median (95% CI) PFS was 3.5 (1.1-not evaluable) months. Six of these patients then received SCT (1 auto-SCT, 5 allogeneic SCT [allo-SCT]), and all of them were alive as of the data cutoff date a median of 24.4 months after third-line therapy initiation.4
In the SOC arm, patients received 2 or 3 cycles of chemotherapy followed by high-dose therapy, with auto-SCT for those with PR or CR; 127 patients required third-line therapy, and 68 of these patients received third-line cellular immunotherapy. Their median (95% CI) PFS was 6.3 (3.4-16.3) months, and OS was 16.3 (8.7-not evaluable) months; ORR was 57%, and the CR rate was 34%.4
The authors of the abstract noted that retreatment with axi-cel as a third line of therapy appeared to be feasible and drive meaningful responses, but outcomes for patients who received subsequent third-line cellular therapy were numerically worse than those for patients who received cellular therapy in the second line. Although the findings must be confirmed by studies with larger sample sizes, these results may help inform treatment decisions after second-line therapy fails.
Hospital vs pharmacy costs. A third abstract leveraged a hospital database to assess health system costs and health care resource utilization associated with CAR T-cell therapy vs SCT for treatment of LBCL.5
In 37 hospital systems nationwide, a total of 852 patients with a mean age of 60 years received treatment with CAR T (n=208), auto-SCT (n=595), or allo-SCT (n=49). Characteristics including age, sex, race, health coverage, and comorbidities were similar across the 3 procedure types. CAR T-cell therapy was less likely to be delivered as an inpatient procedure than auto-SCT (89.9% vs 94.8%; P = .01).
The cost data revealed that the mean cost of CAR T-cell therapy was higher than that of either of the SCT procedures (CAR T, $371,136; auto-SCT, $96,515; allo-SCT, $169,269; P <.001). However, CAR T did carry a lower mean nonpharmacy cost ($41,375 vs $51,778 and $111,594, respectively; P <.001). Mean intensive care unit cost was also lower for CAR T and auto-SCT than for allo-SCT ($86,755 and $86,497 vs $191,980; P <.001).5
Among those treated in the inpatient setting, mean length of stay was shorter for CAR T-cell therapy than for auto-SCT or allo-SCT, at 18 vs 21 and 28 days, respectively (P <.001).5
The authors concluded that although CAR T-cell therapy carried a higher overall price tag driven primarily by pharmacy costs, it imparted less of a burden in terms of hospital utilization. They cautioned that their findings apply only to the hospitals included in their data source.
1. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. FDA. Updated April 1, 2022. Accessed December 17, 2022. https://bit.ly/3RqnXzB
2. U.S. FDA approves Bristol Myers Squibb’s CAR T cell therapy Breyanzi for relapsed or refractory large B-cell lymphoma after one prior therapy. News release. Bristol Myers Squibb. June 24, 2022. Accessed December 17, 2022. https://bit.ly/3W45UAYAbramson JS, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel (liso-cel) versus standard of care (SOC) with salvage chemotherapy followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients with relapsed or refractory large B-cell lymphoma (LBCL): primary analysis of the randomized, phase 3 TRANSFORM study. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Accessed December 19, 2022. https://ash.confex.com/ash/2022/webprogram/Paper159702.html
4. Ghobadi A, Munoz J, Westin J, et al. Outcomes of subsequent anti-lymphoma therapies in patients (Pts) with large B-cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel) or standard of care (SOC) in the second-line (2L) ZUMA-7 study. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Accessed December 19, 2022. https://ash.confex.com/ash/2022/webprogram/Paper158303.html
5. Cui C, Feng C, Rosenthal N, et al. Hospital costs and healthcare resource utilization (HRU) for chimeric antigen (CAR) T-cell therapy and stem cell transplant (SCT) in patients with large B-cell lymphoma (LBCL) in the United States (US). Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Accessed December 19, 2022. https://ash.confex.com/ash/2022/webprogram/Paper157309.html