KarMMA-3 Shows Enhanced HRQOL of Ide-Cel in Previously Treated R/R Multiple Myeloma

The assessment of health-related quality of life for patients with previously treated multiple myeloma was found to be enhanced in the phase 3 KarMMa-3 trial when patients were treated with idecabtagene vicleucel.

Investigators identified significant and meaningful improvements in symptoms, functioning, overall health status, and health-related quality of life when idecabtagene vicleucel (ide-cel; Abcema) was given to patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM) previously treated with 2 to 4 regimens in the phase 3 KarMMa-3 trial (NCT03651128), with results presented at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition.

“These [patient-reported outcome] data highlight the extended [quality of life] benefits of a single infusion with ide-cel compared with the continuous treatment in patients with relapsed/refractory multiple myeloma,” Michel Delforge, MD, PhD, chairman of Leuven Cancer Institute at Leuven University College in Belgium, said during the presentation of the data.

Compared with standard regimens, ide-cel demonstrated significant and meaningful improvements in EORTC QLQ-C30 GHS/QoL and EQ-5D-5L EQ-VAS, observations Delforge noted as “most important” during his presentation. In the EORTC QLQ-C30 GHS/QoL metric, there was an initial steep decline in global health status for patients assigned ide-cel.

“Most likely it was explained by the fact that those patients were not allowed to receive any new type of bridging therapy,” Delforge said.

Shortly after this decline in EORTC QLQ-C30 GHS/QoL scores, there was a rapid increase that exceeded the threshold of minimally important difference. This difference in scores regarding those assigned ide-cel was statistically significant when compared with standard regimens.

Similar observations were made regarding the EORTC QLQ-C30 scale regarding fatigue and pain, where ide-cel also showed a clinically meaningful improvement compared with standard regimens.

Improvements were also observed when assessing physical and cognitive functioning with EORTC QLQ-C30.

“One of the reasons to look at cognitive function in this setting was that there was a potential risk that with ide-cel, shortly after infusion, there could be a decline in cognitive functioning because of neurotoxicity like ICANS,” Delforge explained.

Patients assigned ide-cel also had improvements in disease symptoms and side effects from treatment compared with those assigned standard regimens, as assessed by EORTC QLQ-MY20 models.

Researchers also analyzed between-group differences in all patient-reported outcome domains from baseline to month 25. Of note, the overall lean square mean changes during this time demonstrated significant differences favoring patients assigned ide-cel in 18 out of 21 domains. Also, the difference in overall lean square mean changes exceeded prespecified minimally important difference thresholds for improvement and favored ide-cel in 13 domains.

The time to confirmed improvement was also statistically faster in patients assigned ide-cel compared with standard regimens in 19 out of 21 domains–except for financial difficulty and diarrhea domains.

The time to confirmed deterioration was significantly longer in the ide-cel group vs the standard regimen group for EORTC QLQ-C30 cognitive, emotional and social functioning, constipation, dyspnea, and EORTC QLQ-MY20 treatment-related side effects. Delforge noted more significant differences across domains towards patients assigned ide-cel for time to improvement vs time to deterioration.

In the international, open-label, phase 3 KarMMa-3 trial, researchers assessed health-related quality of life in 386 patients who had received 2 to 4 prior regimens and were randomized 2:1 to ide-cel (n = 254) or standard regimens (n = 132). Delforge noted in his presentation that the overall baseline characteristics of patients in this study were generally balanced between both groups. In addition, patient-reported outcomes at baseline were similar between treatment groups and indicated worse scores compared with the general population.

Several metrics were used to assess health-related quality of life including the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30), EQ-5D-5L, and EORTC Quality-of-Life Questionnaire Multiple Myeloma Module (QLQ-MY20). These assessments were completed during screening at baseline, the day of idecabtagene vicleucel infusion or the first dose of standard treatment, each month starting at month 2 up until 28 months, and every 3 months afterwards. The data cutoff for this analysis was April 28, 2023.

Researchers analyzed an intention-to-treat population and performed comparative assessments using several statistical methodologies, including differences in overall lean square mean changes and time to confirmed improvement or deterioration. Of note, multiplicity adjustment was not conducted, and all P values were nominal (P < .05), Delforge noted.

Patients with triple-class exposed RRMM often have limited treatment options and poor prognosis, in addition to substantial pain, fatigue, and quality of life. Ide-cel is a first-in-class CAR T-cell therapy for those with this specific disease. In the phase 2 KarMMa trial (NCT03361748), ide-cel showed deep and durable responses, as well as improved health-related quality of life in patients with triple-class exposed RRMM.

In an interim analysis of the phase 3 KarMMA-3 trial, with a data cutoff of April 18, 2022, results demonstrated a longer progression-free survival when ide-cel was compared with standard regimens (13.3 months vs 4.4 months, respectively).

Reference

Delforge M, Patel KK, Eliason L, et al. Effects of Idecabtagene Vicleucel (Ide-Cel) Versus Standard Regimens on Health-Related Quality of Life (HRQoL) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Who Had Received 2–4 Prior Regimens: Updated Results from the Phase 3 KarMMa-3 Trial. Blood. 2023;142(1):96. doi:10.1182/blood-2023-179152