CAR-T confers long-term quality-of-life improvement among patients with advanced lymphoma
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Patients with relapsed or refractory diffuse large B-cell lymphoma experienced clinically meaningful improvements in long-term quality-of-life measurements after responding to an infusion of tisagenlecleucel, according to a post hoc analysis of patient-reported outcomes in the JULIET trial published in Blood Advances.
Patients who responded to tisagenlecleucel (Kymriah, Novartis) — an anti-CD19 autologous chimeric antigen receptor T-cell therapy — showed sustained improvement compared with baseline scores in two different health-related quality-of-life assessments, according to the investigators.
“By assessing quality-of-life outcomes, these analyses can provide additional insights into patient care,” lead study author Richard T. Maziarz, MD, medical director of the adult blood and marrow stem cell transplant and cellular therapy program at Oregon Health & Science University Knight Cancer Institute, told Healio.
“We commonly study disease responses in remission rates and, of course, study survival,” he said. “Understanding how people survive is increasingly critical when one wishes to do comparative effectiveness studies.”
Maziarz added that because immune effector cell therapies such as tisagenlecleucel are potentially curative after one dose, his group of investigators felt it was critical to get some insight into how the treatment affects patients’ quality of life (QOL).
QOL assessments
Maziarz and colleagues previously presented a short-term analysis of health-related QOL measures from the JULIET trial that showed clinically meaningful improvements at 3 and 6 months compared with baseline among patients who had a complete or partial response to therapy. The current study extends their previous work to examine whether those improvements were sustained over a longer period (12- and 18-month follow-up).
A total of 115 patients (median age, 56 years, range, 22-76) received a tisagenlecleucel infusion in the JULIET trial, including 99 patients eligible for subsequent evaluation. Researchers previously reported an overall response rate of 54%, with a complete response rate of 40%.
The investigators used the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and Short Form 36 Health Survey Version 2 (SF-36) to evaluate health-related QOL.
In total, 108 patients completed baseline health-related QOL assessments; 57 patients who completed these evaluations achieved either a complete or partial response to therapy. Thirty patients completed the 12-month follow-up questionnaire, whereas 21 patients provided 18-month follow-up responses.
The analysis showed that patients with a complete or partial response to therapy exhibited sustained health-related QOL improvements in all FACT-Lym scores at each follow-up assessment. The largest improvements from baseline related to functional, physical, and social/family domains at 18-month follow-up, with the largest mean change from baseline in the emotional domain occurring at 12-month follow-up.
Researchers also observed improvement that exceeded minimal clinically important differences on five of eight subscales used in the SF-36 evaluations. They included improvements in general health, vitality, physical functioning, role-physical and social functioning.
“One of the most important takeaways from this study is that patients can achieve clinical outcomes that are apparently better than any anticipated continuous therapy could provide,” Maziarz told Healio, adding that many patients saw clinically meaningful improvements in daily functioning with a lack of long-term negative effects.
The study’s largest limitation was the lack of available health-related QOL data from patients who did not have a complete or partial response to therapy. Also, fewer patients who responded to therapy provided responses at 12- and 18-month follow-up, making it difficult for researchers to evaluate the magnitude of the relationship between treatment with tisagenlecleucel and health-related QOL.
Clinical impact
Studies like this should have an impact on clinical practice, especially given the roles of patient choice and health care costs in today’s environment, Maziarz said.
How long and how well someone lives after receiving therapy for advanced disease are significant factors in choosing a therapy like tisagenlecleucel, which is costly and can have serious short-term adverse effects, he added.
“If a patient is given a choice, recognizing that intervention could potentially extend their life but that as a consequence, they will have major cognitive defects for the remainder of their life, many will elect not to pursue the intervention. The additional days of life are not valued as opposed to maintaining the highest quality until the end of life,” Maziarz said. “It is so important that we as physicians and health care providers clearly understand what a patient chooses, rather than what we feel is the best available treatment.”
A major finding of the study is that patients experienced better-than-expected clinical outcomes and that their health-related QOL can return to normal levels rather quickly and be sustained after treatment, which often is not the case for other cancer-related treatments, Maziarz said.
Being armed with this knowledge helps patients and payers determine whether the cost and short-term risks outweigh the potential long-term benefits.
“Socioeconomic issues, as well as prior medical comorbid conditions, influence outcomes. Unless we take all of these into consideration and understand what the patient really wants to gain from therapy, we are not serving them well,” Maziarz said. “Sometimes, being guaranteed life for a shorter period of time is more meaningful than the potential promise of long-term survival.
“Choice is important,” he added. “Often, the patient-reported outcome after the intervention will be most positively impacted by the fact that they had choice.” – by Drew Amorosi
Additional reference:
Maziarz RT, et al. Poster P042. Presented at: European Society for Blood and Marrow Transplantation; March 18-21, 2018; Lisbon, Portugal.
For more information:
Richard T. Maziarz, MD, can be reached at maziarzr@ohsu.edu.
Disclosures: Novartis supported this study. Maziarz reports honoraria from Incyte, Jazz Pharmaceuticals, Juno Therapeutics, Kite Pharma and Novartis; a board of directors and advisory committee role with and research funding from Novartis; consultant roles with Incyte and Juno Therapeutics; and patents and royalties from Athersys Inc. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Courtney Bellomo, MD
The introduction of CAR T cells as a therapy option for patients with DLBCL has revolutionized OS outcomes. Prior to the initiation of these treatments, overall life span was minimal at best and typically quality of life for these patients was negligible. Few studies have evaluated quality of life related to CAR T-cell products greater than 1 year from treatment, and the study by Maziarz and colleagues starts to address these issues.
First, CAR T-cell therapy side effects such as cytokine release syndrome and neurotoxicity may be distressing to patients and their families. Also, at an institutional level, administering these products requires a significant amount of infrastructural resources. The key questions are always, do the side effects outweigh disease control, and are we creating programs that address the side effects safely? The clinical data are a rebounding yes to treating the disease on both fronts, but this study supports that we are also improving patient-reported outcomes. What we are doing to patients is having a meaningful impact overall.
There is still work to be done, however, to restore patients to their former selves. For example, one of the key elements in improvement involved the scores surrounding social and physical functioning. Questions revolving around intimacy, interactions with family and friends, ability to work, and ability to enjoy activities all showed improvement. In contrast, emotional and mental health scores on both surveys seemed to remain stable after 3 months. This seems to suggest that symptoms of anxiety, depression, and thoughts about death and dying are not recovering as quickly as the body is among these patients. Studies like this one remind us that we need better resources to address the emotional component of cancer. As our advances in technology continue, we need to focus on what it means to thrive after cancer and not just survive a disease. We can deliver these products safely and manage short-term side effects, but we also need to also start addressing long-term sequelae. Studies like these are the first step in helping us to frame these questions that need to be investigated in studies moving forward.
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