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High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma.

ABSTRACT: High metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axi-cel. Secondary objectives included finding the association of MTV with response rates and toxicity. The MTV values on baseline positron emission tomography of 96 patients were calculated via manual methodology using commercial software. Based on a median MTV cutoff value of 147.5 mL in the first cohort (n = 48), patients were divided into high and low MTV groups. Median follow-up for survivors was 24.98 months (range, 10.59-51.02 months). Patients with low MTV had significantly superior OS (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.10-0.66) and PFS (HR, 0.40; 95% CI, 0.18-0.89). Results were successfully validated in a second cohort of 48 patients with a median follow-up for survivors of 12.03 months (range, 0.89-25.74 months). Patients with low MTV were found to have superior OS (HR, 0.14; 95% CI, 0.05-0.42) and PFS (HR, 0.29; 95% CI, 0.12-0.69). In conclusion, baseline MTV is associated with OS and PFS in axi-cel recipients with LBCL.

SUBMITTER: Dean EA

PROVIDER: S-EPMC7391155 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma.

Dean Erin A EA Mhaskar Rahul S RS Lu Hong H Mousa Mina S MS Krivenko Gabriel S GS Lazaryan Aleksandr A Bachmeier Christina A CA Chavez Julio C JC Nishihori Taiga T Davila Marco L ML Khimani Farhad F Liu Hien D HD Pinilla-Ibarz Javier J Shah Bijal D BD Jain Michael D MD Balagurunathan Yoganand Y Locke Frederick L FL

Blood advances 20200701 14

High metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) trea ...[more]

PMID: 32702097

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Project description:BackgroundIn a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.MethodsIn this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments.ResultsAmong the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response.ConclusionsIn this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .).

Project description:The ZUMA-7 (Efficacy of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma) study showed that axicabtagene ciloleucel (axi-cel) improved event-free survival (EFS) compared with standard of care (SOC) salvage chemoimmunotherapy followed by autologous stem cell transplant in primary refractory/early relapsed diffuse large B-cell lymphoma (DLBCL); this led to its recent US Food and Drug Administration approval in this setting. We modeled a hypothetical cohort of US adults (mean age, 65 years) with primary refractory/early relapsed DLBCL by developing a Markov model (lifetime horizon) to model the cost-effectiveness of second-line axi-cel compared with SOC using a range of plausible long-term outcomes. EFS and OS were estimated from ZUMA-7. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $150 000 per quality-adjusted life-year (QALY). Assuming a 5-year EFS of 35% with second-line axi-cel and 10% with SOC, axi-cel was cost-effective at a WTP of $150 000 per QALY ($93 547 per QALY). axi-cel was no longer cost-effective if its 5-year EFS was ≤26.4% or if it cost more than $972 061 at a WTP of $150 000. Second-line axi-cel was the cost-effective strategy in 73% of the 10 000 Monte Carlo iterations at a WTP of $150 000. If the absolute benefit in EFS is maintained over time, second-line axi-cel for aggressive relapsed/refractory DLBCL is cost-effective compared with SOC at a WTP of $150 000 per QALY. However, its cost-effectiveness is highly dependent on long-term outcomes. Routine use of second-line chimeric antigen receptor T-cell therapy would add significantly to health care expenditures in the United States (more than $1 billion each year), even when used in a high-risk subpopulation. Further reductions in the cost of chimeric antigen receptor T-cell therapy are needed to be affordable in many regions of the world.

Dataset Information

High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma.

Publications

High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma.

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