ASH Abstracts Show PRO Improvements, Long-Term Efficacy of Cilta-Cel in MM

Abstracts presented at the 2023 American Society of Hematology Annual Meeting and Exposition highlighted improvements in patient-reported outcomes (PROs) with the B-cell maturation antigen (BCMA)–targeting chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel) for multiple myeloma (MM) in the phase 3 CARTITUDE-4 trial (NCT04181827)¹ and updated safety and efficacy data with extended follow-up of the phase 2 CARTITUDE-2 trial (NCT04133636).²

In the CARTITUDE-4 trial, patients who were lenalidomide refractory and had undergone 1 to 3 prior lines of therapy (LOT) experienced clinically meaningful improvements in health-related quality of life (QOL) with cilta-cel treatment compared with patients receiving standard of care (SOC) triplet therapy for relapsed or refractory MM.¹ The findings build upon positive results in the trial’s primary analysis, in which cilta-cel demonstrated better progression-free survival (PFS) vs SOC (HR, 0.26; P < 0.0001) and showed higher response rates as well as response depth.

CAR T cell therapy rendering | Image credit: AIGen - stock.adobe.com

At the time of data cutoff for the new analysis, baseline and 12-month PRO assessments were available for 99 patients in the cilta-cel arm and 66 in the SOC arm. From baseline to month 12, patients in the cilta-cel arm reported improved functioning and symptoms, compared with trends of worsening or less improvement in QOL the SOC arm.

For patients treated with cilta-cel, the least squares mean changes from baseline 12 months were clinically meaningful in the domains of global health status, pain, and the visual analogue scale (10.1 points, –10.2 points, 8.0 points, respectively). Fatigue and emotional functioning were near clinically meaningful thresholds of improvement (–9.1 points and 9.5 points, respectively). In other domains in the EORTC Core Quality of Life questionnaire, results favored cilta-cel numerically, the authors noted.

Median time to symptom worsening was 23.7 months in the cilta-cel arm (95% CI, 22.1-not estimable [NE]) vs 18.9 months (95% CI, 16.8-NE) in the SOC arm, according to the MySIm-Q total symptom scale, which assesses 11 MM-related symptom and 6 impact items.

“These results from the CARTITUDE-4 study showed the potential of cilta-cel to significantly improve health-related quality of life measures for patients, including pain, fatigue and emotional functioning," lead author Roberto Mina, assistant professor, Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy, said in a statement.³ "Cilta-cel has demonstrated deep and durable responses in later lines of therapy, and these results show the potential of cilta-cel for patients with lenalidomide-refractory multiple myeloma as early as after first relapse."

Another abstract provided safety and efficacy data from cohorts A and B of the CARTITUDE-2 study. Cohort A includes patients who have undergone 1 to 3 prior LOT and are lenalidomide refractory, while cohort B includes patients who experienced early relapse less than 12 months after either autologous stem cell transplant (ASCT) or initiation of anti-myeloma treatment if not undergoing ASCT. All patients in both cohorts had not received prior CAR T-cell therapies or anti-BCMA therapies before cilta-cel.

The primary end point was minimal residual disease (MRD) negativity based on next-generation sequencing or next-generation flow cytometry. As of the data cutoff in April 2023, 20 patients in cohort A and 19 patients in cohort B had received cilta-cel, with median follow-ups of 29.9 months and 27.9 months, respectively. High-risk cytogenetics were seen in 35% of patients in cohort A and 12% of patients in cohort B.

There were 17 and 14 patients in cohorts A and B, respectively, who were MRD evaluable. In cohort A, 8 patients (40%) sustained MRD negativity for at least 6 months, while 10 patients (53%) in cohort B showed MRD negativity for at least 6 months. The overall response rates were 95% and 100% in cohorts A and B, respectively. Neither cohort reached median PFS, but 24-month PFS rates were 75% and 73%, respectively. Overall survival rates were 75% and 84%.

Safety profiles were consistent with those seen in previous data and no new safety signals were observed, but 1 additional patient in cohort B experienced grade 2 sensory loss, which resolved.

“These longer-term follow-up data show that patients treated with cilta-cel in earlier LOT, both those with len-refractory MM after 1-3 LOT (cohort A) and those with early relapse (cohort B), experienced deep and durable responses,” the authors concluded. “No new CAR T–related safety signals, except for 1 additional CAR-T cell neurotoxicity in cohort B, were reported. Cohort A provides insight into potential longer-term survival outcomes that may be expected in the phase 3 CARTITUDE-4 trial, which enrolled the same patient population but has shorter follow-up thus far.”

References

1. Mina R, Mylin AK, Yokoyama H, et al. Patient-reported outcomes in the phase 3 CARTITUDE-4 study of ciltacabtagene autoleucel vs standard of care in patients with lenalidomide-refractory multiple myeloma after 1–3 lines of therapy. Presented at: 65th American Society of Hematology Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA. Abstract 1063. https://ash.confex.com/ash/2023/webprogram/Paper178798.html

2. Hillenjgass J, Cohen AD, Agha ME, et al. The phase 2 CARTITUDE-2 trial: updated efficacy and safety of ciltacabtagene autoleucel in patients with multiple myeloma and 1–3 prior lines of therapy (cohort A) and with early relapse after first line treatment (cohort B). Presented at: 65th American Society of Hematology Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA. Abstract 1021. https://ash.confex.com/ash/2023/webprogram/Paper178882.html

3. Treatment with Carvykti (ciltacabtagene autoleucel) resulted in clinically meaningful improvements in health-related quality of life and reduction in disease-specific symptoms in patients with earlier-line multiple myeloma. Johnson & Johnson. News release. December 11, 2023. Accessed December 22, 2023. https://www.prnewswire.com/news-releases/treatment-with-carvykti-ciltacabtagene-autoleucel-resulted-in-clinically-meaningful-improvements-in-health-related-quality-of-life-and-reductions-in-disease-specific-symptoms-in-patients-with-earlier-line-multiple-myeloma-302011900.html