Across 157 unique European CTIS multiple myeloma Phase II and Phase III trial records, progression-free survival (PFS) was the most common endpoint family overall, appearing in 115/157 trials (73.2%). Safety/tolerability followed closely in 114/157 trials (72.6%), while overall survival (OS), overall response rate (ORR), deep response, and minimal residual disease (MRD) formed the core secondary endpoint set. Phase II trials were driven by ORR and safety; Phase III trials shifted toward PFS and MRD as primary decision endpoints.
Measured in any endpoint role, PFS appeared in 115/157 trials (73.2%), safety/tolerability in 114/157 (72.6%), OS in 107/157 (68.2%), and ORR in 104/157 (66.2%). MRD appeared in 87/157 trials (55.4%), confirming its broad use beyond primary endpoint settings.
European multiple myeloma trials are endpoint-dense and survival-oriented: 115/157 trials used PFS and 107/157 used OS, while response endpoints remained almost as common through ORR (104/157) and deep response (92/157). This pattern fits a field where regulatory-relevant disease control, depth of response, and tolerability all remain central.
As primary endpoints, PFS led with 48/157 trials (30.6%), followed by deep response and safety/tolerability at 43/157 each (27.4%), and MRD plus ORR at 41/157 each (26.1%). As secondary endpoints, OS was the most frequent at 102/157 trials (65.0%), followed by PFS in 90/157 (57.3%) and safety in 87/157 (55.4%). Exploratory endpoints were rare, with the leading exploratory family, QoL/PRO, appearing in only 3/157 trials (1.9%).
The primary endpoint layer is split between confirmatory disease control (PFS), depth of response (CR/VGPR/sCR and MRD), and early-phase tolerability. The secondary layer is much broader: OS, PFS, safety, ORR, DOR, MRD, QoL, time-to-progression, PK, and immunogenicity all appear as repeated secondary measurements.
In the Phase II cohort (94 trials), ORR appeared as a primary endpoint in 38/94 trials (40.4%) and safety/tolerability in 37/94 (39.4%). In the Phase III cohort (66 trials), PFS was primary in 40/66 trials (60.6%), while MRD was primary in 24/66 (36.4%).
| Endpoint family | Phase II | Phase III |
|---|---|---|
| Progression-free survival (PFS) | 10.6% | 60.6% |
| Overall response rate / response (ORR) | 40.4% | 6.1% |
| Safety / tolerability | 39.4% | 9.1% |
| Minimal residual disease (MRD) | 20.2% | 36.4% |
| Deep response (CR/VGPR/sCR) | 30.9% | 22.7% |
| Patient-reported outcomes / QoL | 0.0% | 0.0% |
The phase split is clear: Phase II CTIS submissions still rely heavily on activity and tolerability signals, while Phase III submissions move toward PFS and MRD-negative response as confirmatory evidence packages.
Relapsed/refractory multiple myeloma accounted for 68/157 trials (43.3%), followed by general/unspecified multiple myeloma with 47/157 (29.9%) and newly diagnosed/maintenance settings with 33/157 (21.0%). In newly diagnosed/maintenance trials, MRD appeared in 33/33 trials (100.0%) and PFS in 32/33 (97.0%).
| Group | Top endpoint family | Coverage |
|---|---|---|
| Relapsed/refractory MM | PFS / ORR / safety | 47/68 (69.1%) |
| Newly diagnosed / maintenance MM | MRD | 33/33 (100.0%) |
| General / unspecified MM | Safety | 34/47 (72.3%) |
MRD is especially concentrated in newly diagnosed and maintenance settings, where it appears in 33/33 trials. Relapsed/refractory trials are broader and more balanced, with PFS, ORR, and safety each present in 47/68 trials.
Small molecules appeared in 119/157 trials (75.8%), monoclonal antibodies in 94/157 (59.9%), bispecific antibodies in 36/157 (22.9%), cell therapy in 18/157 (11.5%), and antibody-drug conjugates (ADCs) in 16/157 (10.2%). Multi-modality regimens were common, appearing in 113/157 trials (72.0%).
| Modality | Dominant endpoint signal | Coverage |
|---|---|---|
| ADC | ORR and safety | 14/16 (87.5%) |
| Cell therapy | Safety | 13/18 (72.2%) |
| Bispecific antibody | PFS | 28/36 (77.8%) |
| Small molecule | PFS | 103/119 (86.6%) |
The modality pattern supports comparison: ADC trials were highly response- and safety-oriented (14/16 for ORR; 14/16 for safety), while cell therapy retained a prominent safety signal (13/18). Bispecific and small-molecule programs were more survival-oriented, with PFS appearing in 28/36 bispecific trials and 103/119 small-molecule trials.
CTIS initial submission dates and first authorization dates were present for 157/157 trials (100.0%). The median submission-to-first-authorization interval was 45 days across 157/157 trials (100.0%), with authorizations concentrated in 2024 (128/157, 81.5%), followed by 2025 (17/157, 10.8%) and 2026 (12/157, 7.6%). Orphan-drug status appeared in 63/157 trials (40.1%).
The endpoint results are directly relevant to EU regulatory and operational planning because every included record carries CTIS submission and authorization timing. The 45-day median interval provides a practical benchmark when comparing future EU multiple myeloma submissions with similar endpoint complexity.
Patient-reported outcomes and quality-of-life endpoints appeared in 64/157 trials (40.8%), but were more common in Phase III (35/66, 53.0%) than Phase II (31/94, 33.0%). PK/exposure appeared in 47/157 trials (29.9%) and immunogenicity/ADA in 31/157 (19.7%).
The same CTIS data can answer whether EU myeloma trials are adding patient-centered and translational endpoints. The answer is yes for QoL in later-stage development, but PK and immunogenicity remain primarily supportive: PK/exposure was present in 47/157 trials and immunogenicity/ADA in 31/157.
PFS means progression-free survival. OS means overall survival. ORR means overall response rate. MRD means minimal residual disease. DOR means duration of response. QoL/PRO means quality-of-life or patient-reported outcome instruments, including EORTC QLQ-C30, QLQ-MY20, EQ-5D-5L, FACT/FACIT, PRO-CTCAE, and related instruments. PK means pharmacokinetics, including exposure measures such as Cmax, Tmax, AUC, and drug concentration.