CARTITUDE-2 cohorts A and B: Updated efficacy and safety results

The phase II CARTITUDE-2 trial (NCT04133636) evaluated safety and efficacy of the B-cell maturation antigen-directed chimeric antigen receptor T-cell agent ciltacabtagene autoleucel for treatment of relapsed/refractory multiple myeloma.

During 2024 Transplantation & Cellular Therapy Meetings of the ASTCT and CIMBTR (TANDEM), Hillengass.¹ presented updated results from the CARTITUDE-2 trial. We summarize the key results below.

Study design¹

• Cohort A: patients with 1–3 prior lines of therapy
• Cohort B: patients who relapsed at ≤12 months after transplant/at antimyeloma treatment initiation if without transplant
• All patients received a target dose of 0.75 × 10⁶ cells/kg.
• The primary endpoint was negative measurable residual disease at a sensitivity of 10⁻⁵.

Key findings¹

• Cohort A = 20 patients
• Cohort B = 19 patients
• Median follow-up 29 months
• Most patients across both cohorts achieved negative measurable residual disease (Figure 1).

MRD, measurable residual disease.
*Adapted from Hillengass.¹
†Cohort A (n = 17), cohort B (n = 15).
‡Cohort A (n = 11), cohort B (n = 13).
§Cohort A (n = 14), cohort B (n = 13).

• Duration of response, overall survival and progression free survival rates at 24 months were comparable between the two patient cohorts (Table 1).

Table 1. ORR and OS, PFS and DOR rate at 24 months*

DOR, duration of response; ORR, overall response rate; OS, overall survival; PFS, progression free survival. *Adapted from Hillengass.1
	Cohort A (n = 20)	Cohort B (n = 19)
ORR, %	95	100
OS at 24 months, %	75.1	84.2
PFS at 24 months, %	75	73.3
DOR at 24 months, %	73.3	70.5

• Most Grade 3/4 hematologic treatment related adverse events were experienced by more patients in cohort A vs cohort B (Table 2).

Table 2. Cytokine release syndrome, ICANS, and Grade 3/4 hematologic TRAE*

CRS, cytokine release syndrome; ICANS, immune cell associated neurotoxicity syndrome, TRAE, treatment-related adverse event. *Adapted from Hillengass.1
%, unless otherwise stated	Cohort A (n = 20)	Cohort B (n = 19)
Any grade CRS	95	84.2
Any grade ICANS	15	5.3
Hematologic TRAE
Neutropenia	95	89.5
Lymphopenia	80	47.4
Thrombocytopenia	40	26.3
Anemia	45	47.4
Leukopenia	60	31.6

Key learnings
Deep and durable responses were observed with ciltacabtagene autoleucel in earlier lines of treatment, and in patients who experienced early relapse; a population with a current unmet treatment need. These results also provide an early insight into potential clinical outcomes for the ongoing CARTITUDE-4 trial (NCT04181827).