Clinically Meaningful HRQoL Benefits Observed With Ide-Cel in Triple-Class Exposed R/R Myeloma

December 7, 2020
Kristi Rosa

Idecabtagene vicleucel demonstrated clinically meaningful improvements in the quality-of-life of triple-class exposed patients with relapsed/refractory multiple myeloma in the phase 2 KarMMA trial.

Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy, demonstrated clinically meaningful improvements in the quality-of-life (QoL) of triple-class exposed patients with relapsed/refractory multiple myeloma in the phase 2 KarMMA trial (NCT03361748), according to findings presented during the 2020 ASH Annual Meeting & Exposition.1

Results from the secondary QOL data analysis showed that patients on the trial who received ide-cel experienced group-level improvements in the majority of functioning and symptom EORTC QLQ-C30 secondary subscale scores from baseline to month 3 through month 15. Stable status was more commonly reported among individual patients with regard to symptom and financial difficulties subscales. Moreover, scores for the EORTC QLQ-MY20 future perspectives and body image subscales also proved to be stable over time.

At baseline, the health status, as measured by the EQ-5D-5L index, and patient global health assessment, as measured by the EQ-VAS scores, were found to be lower vs the general population in the United Kingdom; however, these scores were found to improve over time with the treatment of the CAR T-cell product.

“These data confirm that in [patients with] triple-class exposed relapsed/refractory myeloma, the clinical benefits associated with ide-cel treatment provide clinically meaningful health-related QoL [HRQOL] improvements without compromising any HRQoL domains,” Nina Shah, MD, hematologist, oncologist, and multiple myeloma researcher at the University of California San Francisco, said in a presentation on the data during the meeting.

Patients with relapsed/refractory multiple myeloma who have been previously exposed to treatment with an immunomodulatory drug, a proteasome inhibitor, and a CD38-targeted antibody and have progressed have few options available to them; no standard of care exists for this population.

Patients with this disease tend to have a high symptom burden, added Shah, with symptoms such as fatigue and bone pain negatively impacting their HRQoL.2,3 When these symptoms become more severe, patients experience a poorer HRQoL, which can consist of worsening social and physical functioning.3,4

Topline data from KarMMA presented during the 2020 ASCO Virtual Scientific Program showed that the CAR T-cell therapy elicited deep and durable responses in heavily pretreated patients with highly refractory disease. Specifically, the overall response rate (ORR) was 73% (95% CI, 65.8%-81.1%; P < .0001), which included a complete response rate of 33% (95% CI, 24.7-40.9; P < .0001), a very good partial response rate of 20%, and a 21% partial response rate.5 Moreover, the median progression-free survival (PFS) was 8.8 months in those who received the drug at the target dose of 150 to 450 ×106 CAR+ T cells. The ORR was even higher, at 82%, in patients who received the BCMA-targeted treatment at the highest target dose of 450 ×106 CAR+ T cells; here, the median PFS was 12.1 months.

These data supported the submission of a biologics license application to the FDA in July 2020 for ide-cel for the treatment of adult patients with relapsed/refractory multiple myeloma.

“An analysis of the impact of ide-cel therapy on primary domains of HRQoL showed that the treatment provides meaningful improvements in QoL and self-reported symptoms associated with relapsed/refractory multiple myeloma,” Shah said.

The single-arm, multicenter phase 2 trial examined the safety and efficacy of ide-cel in adults with triple-class exposed relapsed/refractory multiple myeloma in North America and Europe. In the analysis presented during the 2020 ASH Annual Meeting, investigators sought to evaluate the impact of the CAR T-cell therapy on secondary HRQOL domains of interest and health utility scores.

To evaluate HRQOL, investigators utilized the established EORTC QLQ-C30 (n = 121), the EORTC QLQ-MY20 (n = 120), and the EQ-5D-5L (n = 120) QoL questionnaires; these were completed at screening, baseline, day of infusion, months 1 to 6, and then every 3 months until month 24 or the end of the study, disease progression, or complete remission. Questionnaire compliance rates were higher than 80% for most visits.

On a group level, mean changes from baseline were determined to be clinically meaningful if the point estimate was either above or below the prespecified threshold of minimal important difference (MID). Moreover, mean changes from baseline were considered to be statistically significant when the 95% confidence interval boundaries were either above or below the prespecified threshold of MID. Based on previously published definitions, MIDs were predetermined for each subscale analyzed.

On an individual level, a patient’s score was determined to be either improved or deteriorated if it crossed the prespecified threshold of responder definition (RD).

With the generic cancer validated HRQOL instrument EORTC QLQ-C30, investigators assessed 10 subscales: role functioning, emotional functioning, social functioning, nausea, constipation, diarrhea, insomnia, dyspnea, appetite loss, and financial difficulties.

At baseline, patients enrolled on the trial had a worse level of functioning and a higher symptom burden, as measured on the EORTC QLQ-C30 subscales versus the QLQ-C30 normative data obtained from the general population, according to Shah. Notably, investigators observed clinically meaningful improvements on all functioning secondary subscales. “These improvements were statistically significant, particularly for the role functioning and social functioning subscales, at multiple time points,” Shah said.

Additionally, patients showed stability in gastrointestinal symptoms, including appetite loss, “with a tendency toward a sometimes clinically meaningful decrease,” noted Shah. Clinically meaningful improvements were also observed with regard to insomnia and dyspnea EORTC QLQ-C30 secondary subscales. These scores improved over the course of treatment with a clinically meaningful, and sometimes statistically significant, decrease observed at the majority of time points.

On an individual level, the majority of patients experienced a clinically meaningful improvement or stability on all of the secondary subscales analyzed at month 9. More patients had clinically meaningful improvements in the role functioning, emotional functioning, and social functioning domains at that time point. Stability was most frequently reported for symptom subscales and financial difficulties, noted Shah.

The myeloma-specific module EORTC QLQ-MY20 evaluated future perspectives and boy image using QLQ-C30. Here, patients showed stability with regard to the future perspectives subscale from baseline to months 2 through 15. Moreover, a larger proportion of patients experienced a clinically meaningful improvement or stability in future perspectives and body image subscales at month 9 than at day 1, from baseline.

The EQ-5D-5L questionnaire is a generic instrument that is used to evaluate health status and it is comprised of 2 components: a Health Utility Index, where health status is measured in terms of 5 dimensions, and the Global Health Assessment, where patients evaluate their overall global health status by using the Visual Analogue Scale (VAS). Here, 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

“To allow for comparisons to be made, the responses in these 5 items in the EQ-5D scales were converted to a single utility score using an existing value set,” explained Shah. “In this case, we chose the UK value set. Both the EQ-5D-5L Health Utility Index and the EQ-VAS Global Health Assessment scores were meaningfully lower than the UK general population scores, below the MID at baseline.”

Clinically meaningful improvements in the health utility index and the global health assessment were reported. The majority of patients experienced a clinically meaningful improvement from baseline with regard to both the EQ-5D-5L Health Utility Index and the EQ-VAS Global Health Assessment, Shah concluded.


  1. Shah N, Delforge M, San-Miguel J, et al. Secondary quality-of-life domains in patients with relapsed and refractory multiple myeloma treated with BCMA-directed CAR T cell therapy idecabtagene vicleucel (ide-cel; bb2121): results from the Karmma clinical trials. Presented at: 2020 ASH Annual Meeting & Exposition; December 5-8, 2020; Virtual. Poster 437.
  2. Nijhof IS, van de Donk NWC, Zweegman S, et al. Current and new therapeutic strategies for relapsed and refractory multiple myeloma: an update. Drugs. 2018;78(1):19-37. doi:10.1007/s40265-017-0841-y
  3. Mikhael J. Treatment options for triple-class refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2020;20(1):1-7. doi:10.1016/j.clml.2019.09.621
  4. Johnsen AT, Tholstrup D, Petersen MA, et al. Health related quality of life in a nationally representative sample of haematological patients. Eur J Haematol. 2009;83(2):139-148. doi:10.111/j.1600-0609.2009.01250.x
  5. Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): initial KarMMA results. J Clin Oncol. 2020;38(suppl 5):8503. doi:10.1200/JCO.2020.38.15_suppl.8503