Treatment with tisagenlecleucel was associated with clinically meaningful improvements in health-related quality of life (QoL) over 18 months in patients with diffuse large B-cell lymphoma (DLBCL) who were ineligible for or relapsed after autologous hematopoietic cell transplantation (AHCT) or whose disease was refractory to 2 or more prior lines of therapy, according to an analysis of the JULIET trial.1
Previously, the JULIET investigators had reported durable efficacy of tisagenlecleucel, a CD19-directed genetically modified chimeric antigen receptor autologous T-cell immunocellular therapy, in the relapsed/refractory DLBCL patient population.2 Study author Richard Maziarz, MD, of Knight Cancer Institute at Oregon Health and Science University, and colleagues noted that the improvements in QoL outcomes in this analysis are important because they may help determine which therapies should be used in clinical practice. QoL offers a potential measure of clinical efficacy, and most QoL measures may serve “as a gauge of the value of the treatment in a uniquely patient-centric manner and are increasingly recognized as value measures by payers,” the authors wrote.
The open-label, phase II JULIET trial enrolled adult patients with relapsed/refractory DLBCL who had previously received 2 or more lines of therapy including rituximab and anthracycline, and had either relapsed following or were ineligible for AHCT. Patients were also eligible if they had DLBCL that had transformed from follicular lymphoma or high-grade “double hit” B-cell lymphoma with MYC rearrangements plus rearrangement of BCL2, BCL6, or both.
To measure QoL, the self-administered Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the Short Form 36 Health Survey version 2 (SF-36) questionnaires were completed by each patient prior to clinical assessments and study treatment. The QoL assessments were performed again at months 3, 6, 12, and 18. A score of 0 represented the worst health-related QoL for both instruments.
The majority of patients who completed the QoL assessments were clinical responders to tisagenlecleucel, which may have introduced bias. Nonresponders were less likely to complete the assessments because of either disease progression, death, or study withdrawal.
The improvements in QoL outcomes in this analysis may help determine which therapies should be used in clinical practice.
The rates of questionnaire completion were:
- baseline: 94%
- month 3: 76%
- month 6: 81%
- month 12: 86%
- month 18: 65%
A total of 115 patients with relapsed/refractory DLBCL were infused with tisagenlecleucel at the time of data cutoff. In this cohort, the median age was 56 years (range = 22-76). Most patients (96%) received 2 or more prior systemic therapies, whereas 49% of the infused patients reported a post-AHCT relapse.
Of 115 patients treated with tisagenlecleucel, 99 responded to the drug over a median follow-up period of 19 months and were included in the health-related QoL analysis. Based on responses to the FACT-Lym and SF-36 questionnaires, responders experienced clinically meaningful improvements in QoL over 18 months.
At baseline, the FACT-Lym mean scores were similar within the total patient population group and the group of 57 patients who achieved a complete response (CR) or partial response (PR). For the latter group, the mean scores on two FACT-Lym subscales exceeded their respective minimally clinically important difference (MCID) upper limit at 18 months.
For patients who achieved a CR or PR, scores of the SF-36 subscale also surpassed the MCID at months 3, 6, 12, and 18 for physical functioning, role-physical, social functioning, vitality, and general health domains. The SF-36 subscales demonstrated an overall positive mean change, and the majority of these subscales were above the MCID and correlated with clinically meaningful QoL improvements. All patients, including responders and nonresponders to tisagenlecleucel, surpassed MCID for general health at month 3.
A limitation of this analysis was the assessment of QoL data mostly from responders, including patients who achieved a CR or PR to tisagenlecleucel.
Study authors report relationships with Novartis, which sponsored this trial.
- 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 Adv. 2020;4:629-637.
- Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56.