Table 2.

Ongoing clinical trials of BCMA CAR T therapy to augment response to or replace autologous HCT in multiple myeloma.

Trial	KarMMa-2 NCT03601078	KarMMa-4 NCT04196491	BMT CTN 1902 NCT05032820	CARTITUDE 2 NCT04133636	CARTITUDE 5 NCT04923893
Study Design	Phase 2, multicohort, open- label in clinically high-risk patients with RRMM	Phase 1, single-arm, dose-finding for treatment of high-risk NDMM	Phase 2, single-arm of ide-cel in patients with <VGPR after AutoHCT	Phase 2, multiple, small exploratory cohorts of patients with RRMM at different treatment stages	Randomized, Open Label Phase 3 of frontline therapy in patients in whom AutoHCT is not planned as initial therapy
Control	None	None	None	None	VRd x 8 → Rd
Experimental	Patients receive ide-cel after LDC, assigned to different cohorts	Induction x 3 cycles → Leukapheresis → Bridging x 1 (same as induction) → ide-cel	AutoHCT → Len maintenance x ≥ 6 months → <VGPR → leukapheresis -→ ide-cel → Len maintenance	Patients receive cilta-cel at different treatment stages depending on cohort enrolled	VRd x 6 → Leukapheresis → VRd x 2 bridging → cilta-cel
N	181 (total)	60	40	160 (total)	650
Primary Endpoint	Cohort 1: ORR Cohorts 2: CR rate	DLT rates, AEs	CR rate	MRD- rate after 1 yr	PFS
Key Secondary Endpoints	TTR, DOR, PFS, TTP, OS, AEs, MRD- rate, HRQoL, PK	CR rate, ORR, DOR, TCR, feasibility of initiating maintenance, PFS, OS, PK	Disease progression, best response, NRM, AEs, OS, maintenance feasibility, CAR T expansion and persistece	ORR, ≥VGPR, CBR, DOR, TTR, MRD- CR rate after 1 yr, AEs	Sustained MRD-, MRD- rate at 9 mo, MRD- CR rate, OS, ≥CR rate, PFS2, AEs, CAR T activation, expansion, persistence, HRQoL
Key Eligibility	Cohort dependent. • 1: RRMM subjects with ≥ 3 prior with rapid progression to most recent • 2a: R-ISS III and PD • <18 mo of induction + AutoHCT +Len • 2b: R-ISS III and PD • <18 mo since start of initial therapy, no AutoHCT • 2c: R-ISS III and <VGPR 70 to 110d post AutoHCT Measurable disease. ECOG ≤ 1. No CNS involvement, plasma cell leukemia, clinically significant chronic diseases, AutoHCT < 12 weeks from leukapheresis.	NDMM, measurable disease, R-ISS III, ECOG ≤ 1. Must not receive Dara with cycles 2 or 3, and no dexamethasone with cycle 3. Adequate hematologic parameters and organ function, no CNS involvement, no clinically significant comorbidities	AutoHCT (with melphalan > 140mg/m2) within 12 months, <VGPR after at least 6 months Len maintenance, adequate performance status, organ function, hematologic parameters; no prior AlloHCT, CNS, PCL, or amyloidosis; must have measurable disease, no clinically significant medical comordibities	Cohort dependent. • A: PD after 1–3 lines • B: early relapse after 1st line • C: prior PI, IMID, CD38, and BCMA tx • D: <CR after 1st line AutoHCT • E: 1st line high risk with no AutoHCT planned • F: 1st line standard risk after initiation of therapy Measurable disease. ECOG ≤ 1. No major ongoing toxicity from prior therapy. No CNS involvement	NDMM with measurable disease at screening, ECOG ≤ 1, no planned AutoHCT as initial treatment, adequate hematologic and organ function, no CNS involvement or hepatitis B or C

RRMM, relapsed/refractory multiple myeloma; LDC, lymphodepleting chemotherapy; ORR, overall response rate; CR, complete response; TTR, time-to-response; DOR, duration of response; TTP, time-to-progression; HRQoL, health-related quality of life; R-iSS, revised International Staging System; Len, lenalidomide; NDMM, newly-diagnosed multiple myeloma; PCL, plasma cell leukemia; CBR, clinical benefit rate; PI, proteasome inhibitor; IMID, immunomodulatory drug; BCMA, B-cell maturation antigen; PFS2, progression-free survival after second-line therapy.