|The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Patients undergoing bridging therapy between apheresis and lymphodepleting chemotherapy during the production of axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory large B-cell lymphoma (LBCL) had poorer lymphoma-specific and overall survival compared with patients who did not undergo bridging therapy, according to findings from a large multicenter cohort study described in a pre-meeting abstract for the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.
However, patients in the bridging cohort also had poorer prognostic factors at baseline, the study authors noted.
“This inferior outcome raises the possibility that bridging therapy may identify a subgroup of lymphoma patients with a different biology, or alternatively, bridging therapy may have an effect on the host or the tumor microenvironment that may impact CAR-T efficacy,” reported lead author Michael D. Jain, MD, PhD, of the department of blood and marrow transplant and cellular immunotherapy, Moffitt Cancer Center, Tampa, Florida.
They called for prospective studies of bridging strategies to learn whether bridging can broadly improve outcomes for this patient population or should be employed only for patients with emergent disease during axi-cel manufacture.
With or without bridging, approximately 8% of patients in the series did not receive axi-cel due to lymphoma progression and/or death, infection, renal failure, or because they achieved complete response with bridging therapy. “In addition, there may have been patients where bridging prevented progression or death prior to axi-cel infusion,” the researchers noted in the abstract.
Bridging therapy for lymphoma can involve steroids, chemotherapy, radiotherapy or targeted therapies.
The US Lymphoma CAR T Cell Consortium has seventeen US academic center member institutions that share data from lymphoma patients undergoing standard-of-care CAR-T therapy. There were 298 patients who underwent apheresis with the intent to manufacture axi-cel for LBCL at these centers. Of these, 275 patients received a CAR-T infusion. Interestingly, 7 of these patients received the infusion through the expanded access program ZUMA-9.
At a median follow-up of 13.9 months, 158 of 298 apheresed patients (53%) received bridging therapy and 140 (47%) did not. Twenty-three percent of patients received steroids alone as bridging therapy; 54% received chemotherapy, 12% underwent radiotherapy and 10% were administered targeted therapies.
There were baseline differences between patients who underwent bridging therapies and those who did not. A higher proportion of patients in the bridging therapy group had an ECOG score of 2 to 4, bulky disease greater than 10 cm, an International Prognostic Index of 3 to 5, a higher lactate dehydrogenase level at conditioning, and did not meet ZUMA-1 eligibility.
Patients who underwent bridging therapy vs those who did not had higher rates of grade 3 of higher neurotoxicity (34% vs 28%, respectively), grade 3 or higher cytokine release syndrome (9% vs 5%, respepctively), nonrelapse mortality (7.1% vs 1.5%, respectively), and death after lymphoma relapse at 12 months after axi-cel infusion (37% vs 17%, respectively).
Although the efficacy of axi-cel was comparable across bridging strategies, bridging was associated with worse progression-free survival and overall survival compared with patients who did not undergo bridging therapy, the authors noted.
The use of bridging before CAR-T for LBCL should not be totally abandoned, however; the investigators acknowledged that some patients may have died or been unable to receive CAR-T at all without bridging.
“We currently do not recommend that all patients should be given bridging while awaiting axi-cel manufacturing,” the authors said in conclusion.
Disclosure: Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.
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Jain MD, Jacobs MT, Nastoupil LJ, et al. Characteristics and outcomes of patients receiving bridging therapy while awaiting manufacture of standard of care axicabtagene ciloleucel CD19 chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory large B-cell lymphoma: Results from the from the US Lymphoma CAR-T Consortium. Presentation at: American Society of Hematology 61st Annual Meeting and Exposition; December 7-10; Orlando, FL. Abstract 245.