Long-term Follow-up from Phase II JULIET Study Suggests Durable Improvement in HRQoL


These data, in combination with durable complete responses and overall survival data, suggested that tisagenlecleucel improved health-related quality of life in adult patients with relapsed or refractory diffuse large B-cell lymphoma who respond to treatment.

Long-term follow-up data from the phase II JULIET study, published in Blood Advances, indicated that adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who responded to tisagenlecleucel (Kymriah) therapy experienced a durable improvement in health-related quality of life (HRQoL).1

These data, in combination with the durable complete responses and overall survival data there were previously reported, suggested that tisagenlecleucel improves HRQoL in patients with relapsed or refractory DLBCL who responded to this therapy. This report will now serve as a benchmark for understanding the HRQoL benefits of future novel treatments in this disease space and will also serve as a new baseline for comparison and evaluation of CD19-targeted CAR T-cell therapies. 

“Many patients with this advanced level of disease become depressed and withdraw, but here patients reported improved functional status, physical capabilities, and ability to interact with people,” lead author Richard Maziarz, MD, of the Oregon Health & Science University School of Medicine, said in a press release.2“As we progress in our capacity to offer therapies to treat cancers, we have to ask: Is it enough to just have our patients in remission or alive, or do we want them to be able to truly live again, and to re-enter society with full function?” 

This study enrolled patients who were ≥18 years of age with relapsed or refractory DLBCL after ≥2 lines of therapy and had either undergone a failed autologous stem cell transplant or were ineligible for the procedure. The participants were infused with a single dose of tisagenlecleucel, and researchers used 2 validated HRQoL instruments-Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and Short Form-36 (SF-36) Health Survey-to measure HRQoL at baseline and months 3, 6, 12, and 18. 

At the data cutoff of May 21, 2018, 115 patients had received tisagenlecleucel infusion, and 99 patients were evaluated. Of that cohort, the overall response rate was 54%, and 40% of patients achieved a complete response (CR). Originally, 108 patients completed the HRQoL assessments at baseline, including 57 patients who eventually achieved CR or partial response (PR). Moreover, 30 and 21 patients in clinical response who completed assessments at baseline also completed assessments at months 12 and 18, respectively. 

Those who achieved CR or PR sustained HRQoL improvement in all FACT scores at all time points. Furthermore, SF-36 instruments showed improvement above the minimal clinically important differences on 5 of the 8 subscales. However, a notable limitation of the study was that most of the HRQoL data were only available from infused patients who received CR or PR, and most patients who did not complete the HRQoL assessments discontinued the study or were lost to follow-up. 

“Although we chose to assess HRQoL using the disease-specific instrument FACT-Lym and the more general disease instrument SF-36, other instruments such as Patient-Reported Outcomes Measurement Information System (PROMIS) will be beneficial to include in future clinical trials for CAR T-cell therapy,” the authors wrote. “These data, in conjunction with the results of the current study, strongly suggest that patients who respond to tisagenlecleucel therapy may produce clinically meaningful improvements in patient-reported HRQoL across at least 2 hematologic malignancies.”

As ongoing CAR T-cell therapy trials are completed, the researchers indicated that these results could help to provide insight on the use and timing of patient-reported outcome questionnaires in future clinical research of CAR T-cell therapies. Additionally, Maziarz suggested that he and his team hope the findings about quality of life improvement will also support the value of the therapy.

“The high price of health care is in the news daily. Is it worth it? What is the value of our clinical interventions? We want to know that we are not just adding extra days to a patient’s life, but that those extra days are meaningful to them.”

The public list price for tisagenlecleucel in the US, according to a study published in JAMA Oncology, is $475,000.3

The findings were initially presented at the Transplantation and Cellular Therapy Meeting, held from February 20-24, 2019, in Houston, Texas, and at the 44th annual meeting of the European Society for Blood and Marrow Transplantation, held from March 18-21, 2018, in Lisbon, Portugal. 


1. Maziarz RT, Waller EK, Jaeger U, et al. Patient-reported long-term quality of life after tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma. Blood Advances. doi:10.1182/bloodadvances.2019001026.

2. New study finds cellular immunotherapy treatment associated with improved quality of life [news release]. Washington. Published February 19, 2020. prnmedia.prnewswire.com/news-releases/new-study-finds-cellular-immunotherapy-treatment-associated-with-improved-quality-of-life-301007693.html. Accessed February 20, 2020. 

3. Furzer J, Gupta S, Nathan PC, et al. Cost-effectiveness of Tisagenlecleucel vs Standard Care in High-risk Relapsed Pediatric Acute Lymphoblastic Leukemia in Canada. JAMA Oncology. doi:10.1001/jamaoncol.2019.5909.

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