Tisagenlecleucel led to clinically meaningful and durable improvements in health-related quality of life in patients with relapsed/refractory diffuse large B-cell lymphoma who achieved a complete or partial response to the CD19-directed CAR T-cell therapy in the phase 2 JULIET trial.
Richard T. Maziarz, MD
Tisagenlecleucel (Kymriah) led to clinically meaningful and durable improvements in health-related quality of life (HRQoL) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who achieved a complete or partial response (PR) to the CD19-directed CAR T-cell therapy in the phase 2 JULIET trial, according to results of a study published in Blood Advances.1
At a median follow-up of 19.3 months among 99 evaluable patients, the overall response rate (ORR) was 54%, and the complete response (CR) rate was 40%. Patients who achieved CR or PR experienced a sustained improvement in HRQoL in all Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scores at all time points. Additionally, the Short-Form-36 (SF-36) Health Survey showed improvements above the boundary for minimal clinically important differences on 5 of 8 subscales.
"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 study author, Richard T. Maziarz, MD, of Oregon Health and Science University School of Medicine, stated in a news 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?"
In May 2018, tisagenlecleucel received an FDA approval for use in adult patients with relapsed/refractory large B-cell lymphoma—including DLBCL, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma—after 2 or more lines of systemic therapy.
The approval was based on earlier data from the phase 2 JULIET trial, in which adult patients with relapsed/refractory DLBCL received a single infusion of the CD19-directed CAR T-cell therapy. Initial findings showed that tisagenlecleucel led to an ORR of 50% (95% CI, 38%-62%), a CR rate of 32%, and a PR rate of 18%.3
Updated findings, which were published in the New England Journal of Medicine in January 2019, showed an ORR of 52%, a CR rate of 40%, and a PR rate of 12%.4
In this analysis, the FACT-Lym and SF-36 questionnaires were used to measure HRQoL at baseline and months 3, 6, 12, and 18 in patients who had received a single infusion of tisagenlecleucel (n = 115).
Patients who received tisagenlecleucel had a median age of 56 years (range, 22-76), and 23% were at least 65 years of age. Additionally, 96% had received at least 2 prior systemic therapies, and 49% had relapsed after autologous stem cell transplant.
The FACT-Lym survey was used to assess the QoL in patients with lymphoma and included the FACT-General (FACT-G) and the lymphoma subscale (Lym S; score range, 0-168). The FACT-G consists of 27 questions that encompass physical, social/family, emotional, and functional well-being. Lym S is a 15-question survey that assesses patient responses to lymphoma-associated treatment and symptoms, as well as disease and treatment-related symptoms, such as pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite.
The SF-36 questionnaire consists of 8 subscales that reflect physical functioning, emotional and physical health problems that limit role functioning, physical pain, general health perception, vitality, social functioning, and mental health. Each subscale was scored separately, and 2 total scores for the physical component and the mental component were calculated (score range, 0-100).
Higher scores on the FACT-Lym and SF-36 assessments were associated with improved HRQoL. Study-specific HRQoL assessments were discontinued when patients developed progressive disease during the study.
At baseline, 108 patients (94%; N = 115) completed HRQoL assessments, including 57 patients who achieved a best response of CR or PR (N = 60). Additionally, 30 and 21 patients in CR or PR who completed a baseline assessment also completed an assessment at 12 and 18 months, respectively.
The mean change in the total FACT-Lym score from baseline among patients who achieved CR or PR increased by 9.4, 8.6, 9.6, and 13.1 points at months 3, 6, 12, and 18, respectively.
The highest mean change from baseline occurred at 18 months for functional, physical, and social/family FACT-G categories. The largest mean change from baseline in the emotional category was reported at month 12.
Among patients who achieved CR or PR, the mean SF-36 subscale scores exceeded the boundary for minimal clinically important differences at months 3, 6, 12, and 18 for general health (+ 9.73), vitality (+ 6.75), physical functioning (+ 6.1), role-physical (+ 8.83), and social functioning (+ 11.6).
At 3 months, all patients, irrespective of response, exceeded the minimal clinically important differences boundary for general health. At months 3, 6, and 12, patients experienced a numeric improvement in mental health from baseline assessments. At months 3, 6, and 18, patients experienced clinically meaningful improvements in bodily pain compared with baseline assessments.
The total physical health score led to an improvement in the mean change from baseline above the minimal clinically important differences boundary at months 3, 6, and 18.
Approximately 80% who received tisagenlecleucel completed the HRQoL assessments within 1 year. The most common reasons for not completing the questionnaires were disease progression and death. Among the 115 patients who received tisagenlecleucel, 56.5% (n = 65) experienced disease progression, 44 of whom died by 1 year, and 12 of whom died by month 18.
"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," Maziarz stated in the news release.
Tisagenlecleucel is also approved by the FDA for use in patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse.