HRQOL Decreased During and Immediately After CAR T-Cell Therapy for DLBCL

Prior to chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), patients experienced a decrease in health-related quality of life (HRQOL), which was further impaired during and immediately after CAR T therapy.

Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have often exhausted multiple lines of therapy. These patients had a low health-related quality of life (HRQOL) prior to treatment with chimeric antigen receptor (CAR) T-cell therapy, and patients also reported impairment across key domains of HRQOL during CAR T treatment.

The findings of this study on patient perspectives of HRQOL during CAR T-cell therapy were published in Oncology and Therapy.

Patients with R/R DLBCL have significant morbidity and mortality, the authors explained. Chemoimmunotherapy with rituximab-cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone (R-CHOP) is the current standard of care (SOC), but it is only effective in approximately half of patients. Patients who relapse or who are nonresponders are treated with high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

“Studies have demonstrated that R/R DLBCL patients receiving SOC therapy report decreases in HRQOL across numerous domains including physical functioning and emotional well-being,” the authors wrote. “Similarly, CAR T therapy is associated with potentially severe adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which can significantly impair patient functioning and HRQOL.”

Patient-reported outcomes (PROs) are being used to capture the patient perspective and are included in clinical trials to complement clinical outcomes.

The authors conducted a targeted literature review to inform the development of an interview guide comprised of open-ended questions. They held 2 focus groups with a total of 18 patients with DLBCL who had received CAR T-cell therapy. The first focus group was conducted live in November 2019. The second focus group was conducted in July 2020 via Zoom due to the pandemic.

The mean age of the patients was 60 years, and 60% were male. In addition, 89% were Caucasian. The average time since DLBCL diagnosis was 6.6 years and the average time since CAR T-cell treatment was 1.4 years.

The researchers identified 8 main domain impairments: social functioning, emotional functioning, fatigue, physical functioning, cognitive functioning, role functioning, sleep, and pain/discomfort. They found the following results:

Social functioning. The majority (72%) noted difficulty maintaining relationships and a lack of fulfillment in their social lives. In the second focus group, 100% endorsed social functioning impairments during and after CAR T therapy compared with 57% before. Overall, 33% highlighted lasting limitations 6 months after therapy

Emotional functioning. A total of 61% of patients reported struggling with their emotional well-being prior to CAR T therapy, and 72% noted the impact during and immediately after therapy. However, 6 months after treatment, only 39% endorsed emotional impact.

Physical functioning. Prior to CAR T therapy, 39% reported difficulty in physical functioning, and this proportion increased to 67% during and immediately after CAR T therapy. The lasting impairments were not as severe as those experienced during or immediately after therapy.

Cognitive and role functioning. Only 28% of patients highlighted impairments of cognitive functioning and role functioning. More patients reported impairments during and immediately after CAR T therapy. Commonly cited cognitive impairments were neurological adverse events like delirium, confusion, and seizures.

Sleep. Only 22% of patients reported sleep impairment before CAR T therapy, with a larger share (44%) reporting sleep impairment immediately after. Six months after therapy, the share declined to 33% but didn’t return to the level prior to therapy. This impairment was not considered particularly severe or bothersome by patients.

Fatigue and pain/discomfort. Half of the patients experienced fatigue prior to their CAR T therapy and noted that they “struggled to isolate the cause of their fatigue because their prior DLBCL treatments left them with reduced energy levels.” Most patients (72%) experienced new onset or increased intensity of fatigue during and immediately after therapy. By 6 months after therapy, 56% still reported experiencing fatigue, but their energy levels were improving. Only 1 patient reported preexisting pain and an additional 6 patients reported pain during and immediately after CAR T therapy. Eight patients continued to experience persistent pain 6 months after therapy.

“This study suggests that the current PRO domains commonly used to assess DLBCL are appropriate for assessing patients treated with CAR T,” the authors concluded. “Identifying and understanding the relevance of these domains for CAR T patients can help clinicians better understand this population’s needs and treatment journey and help inform the selection and use of PROs in future studies…”

Reference

Cheng R, Scippa K, Locke FL, Thornton Snider J, Jim H. Patient perspectives on health-related quality of life in diffuse large B-cell lymphoma treated with CAR T-cell therapy: a qualitative study. Oncol Ther. Published online November 15, 2021. doi:10.1007/s40487-021-00174-0