Achieving a complete response (CR) or partial response (PR) to bridging therapy is associated with better outcomes following chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory (R/R) large B-cell lymphoma (LBCL), with bridging regimens that contain polatuzumab faring the best, according to study results reported in Blood Advances. Researchers noted these findings support wide use of bridging therapy and proceeding with CAR T-cell therapy even after a CR to bridging therapy.
“We found bridging therapy to be safe, and we saw that response to [bridging therapy] was a pretty sensitive marker for better outcomes following CAR-T,” said Claire Roddie, MD, PhD, lead author and a consultant hematologist at University College London in the U.K.
Researchers pulled data from electronic medical records for consecutive patients with R/R LBCL from the U.K. National CAR Clinical Panel (NCCP), to which patients are submitted for consideration for CD19 CAR-T treatment. Additional patients were included from the Scottish CAR-T center, an equivalent of the NCCP.
Cases were divided into those not receiving bridging therapy, corticosteroids alone, chemotherapy, radiotherapy, and combined modality (CMT) such as chemotherapy and radiotherapy. Chemotherapy was further grouped by high-dose (HDT), low-dose (LDT), and rituximab-bendamustine-polatuzumab (RBP).
The study included 375 patients who underwent CD19 CAR-T therapy between December 2018 and November 2020.
The patients bridged with chemotherapy were more likely than those who did not receive bridging to have stage 3 or 4 disease and were more likely to have extranodal disease and an Eastern Cooperative Oncology Group (ECOG) score of 1 rather than 0. Those receiving radiotherapy bridging had significantly less stage 3 or 4 disease and less extranodal disease than patients undergoing chemotherapy.
The researchers noted that more intensive approaches to bridging were used over time, with more chemotherapy and radiotherapy being used later in the study period. And RBP became the “regimen of choice” from June 2019 through the Early Access to Medicines Scheme, which gives patients who are seriously ill access to medications that haven’t yet received marketing approval.
Overall response rates to bridging therapy were higher with radiotherapy and RBP – 65% and 42%, respectively, compared to 18% for LDT, 29% for HDT, and 33% for CMT.
Those with a CR or PR to bridging therapy, not including those receiving corticosteroids only, had a one-year progression-free survival (PFS) rate of 50.1% compared to 29.7% for those who did not have a response, researchers reported.
Researchers performed a multivariable analysis to assess the association between response to bridging therapy and PFS after CAR-T therapy, while accounting for other pre-treatment factors. According to this analysis, those with a CR or PR to bridging had a 42% reduced risk of progression or death compared to non-responders. They also found the modality of bridging was not predictive; “responders did well regardless of how the response was achieved,” they noted.
Bridging with RBP was independently associated with a higher likelihood of response to bridging therapy, with patients treated with RBP twice as likely to achieve a response as compared to the other forms of chemotherapy (odds ratio vs. LDT or HDT = 2.21; p=0.010). Response to the previous line of therapy and the absence of bulky disease were also independently associated with response to bridging therapy; those who achieved a PR or a CR to a previous line of therapy were more likely to have a response to bridging than those whose disease was stable or progressive disease after a previous line of therapy.
“Our position is that polatuzumab should be strongly considered as a bridge to CAR-T in all suitable patients,” Dr. Roddie said.
Bridging was not associated with an increase in non-relapse mortality, with chemotherapy-bridged patients having a similar non-relapse mortality rate as those who did not receive bridging.
The authors acknowledged some limitations to their retrospective data analysis. They performed multiple comparisons, had small numbers in some treatment groups, and analyzed the effect of non-randomized treatment modalities and regimens where there was clearly a treatment selection bias that may not be overcome with the use of multivariable analyses. Despite these limitations, they said, the data suggest bridging therapy before CAR T-cell therapy can lead to better outcomes.
“In our view, physicians should view [bridging therapy] as an opportunity to substantially improve CAR-T [intention-to-treat] and outcomes, particularly in patients achieving CR/PR to [bridging therapy],” Dr. Roddie said. “We suggest that patients in CR following [bridging therapy] should proceed with CAR-T as planned despite the lack of measurable disease, as these are the patients with the best CAR-T outcomes in our analysis.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Roddie C, Neill L, Osborne W, et al. Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma [published online, 2023 Feb 1]. Blood Adv. doi: 10.1182/bloodadvances.2022009019.
