Editor’s Note: From April 14 to 17, 2024, the 50th European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting was grandly held in Glasgow, UK, a city renowned for its historical significance. This year marks the 50th anniversary of EBMT, and the event gathered leading figures in the field of hematopoietic stem cell transplantation and over 6,000 hematology experts from around the world. The attendees reviewed the remarkable achievements in the fields of hematology and bone marrow transplantation over the past 50 years and explored forward-looking patient management strategies. At the conference, chimeric antigen receptor T-cell (CAR-T) therapy, a highlight of this meeting, showcased a series of breakthroughs in the treatment of multiple myeloma and lymphoma, attracting significant attention. This issue features a special invitation to Professor Jun Ma from the Harbin Institute of Hematological Oncology to provide an insightful interpretation of five major research studies in the field of CAR-T cell therapy. Here, we present a compilation of these insights for our readers.
Study Background
This phase III CARTITUDE-4 study (NCT04181827) compared the efficacy of ciltacabtagene autoleucel (cilta-cel) to standard of care (SOC) treatments—either pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone—in patients who had received 1-3 previous lines of therapy (LOT). Preliminary analysis showed that cilta-cel significantly improved progression-free survival (HR, 0.26; P<0.0001). The study reported adjusted patient-reported outcomes (PROs) for both groups.
Study Methods
The study included 419 patients previously treated with lenalidomide and who had received 1-3 lines of therapy, including proteasome inhibitors (PI) and immunomodulatory drugs (IMiD). Patients were randomly assigned to either the cilta-cel (n=208) or SOC (n=211) group. All patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30; 100-point scale), EuroQoL 5-dimension 5-level (EQ-5D-5L; 100-point scale), and Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q; 5-point scale), until disease progression. Symptom worsening time was assessed using the Kaplan-Meier method, defined as a clinically meaningful increase (≥0.5 standard deviation from baseline summary score) without subsequent reduction in multiple myeloma symptoms.
Study Results
As of November 1, 2022, 99 patients in the cilta-cel group and 66 in the SOC group had completed baseline and 12-month PRO assessments, representing data prior to disease progression. Compliance with PROs was 100% at baseline, declining to 74% in the cilta-cel group and 81% in the SOC group at 12 months. Compared to baseline, patients in the cilta-cel group reported improvements in function and symptom reduction, while the SOC group’s PRO scores tended to either worsen or show lesser improvement in most areas and symptoms. For cilta-cel patients, average improvements from baseline to 12 months exceeded clinically meaningful thresholds for global health status (10.1 points), pain (-10.2 points), and visual analogue scale (8.0 points); improvements in fatigue (-9.1 points) and emotional function (9.5 points) approached clinically meaningful thresholds. In all other EORTC QLQ-C30 scales, results numerically favored cilta-cel. On the MySIm-Q total symptom scale, the median time until worsening of multiple myeloma symptoms was 23.7 months (95%CI: 22.1-not estimable) for the cilta-cel group compared to 18.9 months (95%CI: 16.8-not estimable) for the SOC group (HR=0.42).
Study Conclusion
Patients with multiple myeloma who had previously been treated with lenalidomide and had received 1-3 lines of prior therapy showed clinically meaningful improvements in health-related quality of life (HRQoL) and significant reductions in disease-specific symptoms after a single infusion of cilta-cel. Compared to SOC, improvements with cilta-cel were more significant in all assessed domains. Combined with previously reported data, cilta-cel significantly enhanced clinical outcomes, highlighting its potential as a new treatment option for patients with refractory multiple myeloma after first relapse.
Expert Commentary
This Phase III CARTITUDE-4 study compared cilta-cel to standard treatment in patients with multiple myeloma who had received 1-3 prior lines of therapy (LOT). It particularly focused on demonstrating clinically meaningful improvements in HRQoL (health-related quality of life) and significant reductions in disease-specific symptoms. Compared to the standard of care (SOC), improvements in HRQoL were more pronounced with cilta-cel. As the survival duration for patients with multiple myeloma extends, there is an increasing emphasis on improving quality of life and managing disease-specific symptoms, not just prolonging life but enhancing its quality. As physicians, we should also aim to help patients better reintegrate into society, their careers, and their families. The CARTITUDE-4 trial provides a new treatment option for patients experiencing their first relapse.
