Clinical Trial Intelligence

Does PFS Displace OS as the Primary Endpoint in Phase III Lymphoma Trials?

30 May 2026

Across 73 CTIS-derived lymphoma Phase III endpoint records authorized in 2024–2026, PFS was the dominant primary survival endpoint while OS did not appear as a primary endpoint in the analyzed cohort. OS remained highly visible as a secondary or follow-up endpoint, suggesting that lymphoma Phase III dossiers are using OS mainly as confirmatory survival context rather than as the primary statistical anchor.

73
Included lymphoma Phase III endpoint records
61.6%
Used PFS as a primary endpoint
0.0%
Used OS as a primary endpoint
78.1%
Retained OS as secondary or follow-up endpoint

PFS Was the Primary Survival Endpoint; OS Was Not Used as Primary

PFS appeared as a primary endpoint in 45 of 73 trials (61.6%). OS appeared as a primary endpoint in 0 of 73 trials (0.0%).

Primary Endpoint Use: PFS vs OS
PFS primary
45 / 73
OS primary
0 / 73
Other primary
28 / 73
OS vs PFS in Lymphoma Phase III Trials
Interpretation

The observed pattern is not a balanced OS-versus-PFS split. PFS functions as the main primary survival endpoint, while OS is largely displaced from primary endpoint status in this lymphoma Phase III cohort.

PFS Primary Use Was Stable Across Authorization Years

PFS was primary in 34 of 54 2024 trials (63.0%), 8 of 15 2025 trials (53.3%), and 3 of 4 2026 trials (75.0%).

PFS Primary Endpoint by Authorization Year
2024
34 / 54
2025
8 / 15
2026
3 / 4
OS vs PFS in Lymphoma Phase III Trials
Interpretation

The endpoint pattern does not appear to be a single-year anomaly. PFS remained the main primary survival endpoint across all three authorization years, while OS remained absent as a primary endpoint in each year.

OS Was Preserved as Secondary Evidence in Most Trials

OS was listed as a secondary or follow-up endpoint in 57 of 73 trials (78.1%). This included 42 of 54 trials in 2024, 12 of 15 in 2025, and 3 of 4 in 2026.

OS Endpoint Placement
Primary OS
0
0.0% of trials
Secondary OS
57
78.1% of trials
No OS listed
16
21.9% of trials
OS vs PFS in Lymphoma Phase III Trials
Interpretation

OS is not absent from lymphoma Phase III evidence plans; it is repositioned. The dominant pattern is PFS as the primary efficacy endpoint with OS retained as a longer-horizon survival measure.

PFS Primary Use Was Strongest in CLL/SLL and Indolent B-Cell Settings

PFS was primary in 18 of 23 CLL/SLL/Richter trials (78.3%), 14 of 25 aggressive B-cell/DLBCL trials (56.0%), 10 of 15 follicular/mantle/marginal-zone trials (66.7%), and 3 of 10 Hodgkin/cutaneous/other lymphoma trials (30.0%).

PFS Primary Use by Lymphoma Segment
CLL / SLL / Richter
18 / 23
Indolent B-cell
10 / 15
DLBCL / aggressive B-cell
14 / 25
Hodgkin / cutaneous / other
3 / 10
OS vs PFS in Lymphoma Phase III Trials
Interpretation

The strongest PFS-primary signal appeared in chronic and indolent B-cell lymphoma programs, where disease-control duration is central to trial design. Aggressive and special-population studies showed more endpoint diversification, but still did not shift OS into the primary position.

When PFS Was Not Primary, Response and Special-Purpose Endpoints Filled the Gap

Among the 28 trials without PFS as a primary endpoint, 17 used response, complete response, ORR, MRD, or PET-response endpoints (60.7%), while 11 used EFS/DFS, safety, infection, composite, or other endpoints (39.3%).

Non-PFS Primary Endpoint Types
Response / CR / MRD
17
60.7% of non-PFS primaries
EFS / DFS
4
14.3% of non-PFS primaries
Safety / run-in
4
14.3% of non-PFS primaries
Composite / infection / other
3
10.7% of non-PFS primaries
OS vs PFS in Lymphoma Phase III Trials
Interpretation

The alternative to PFS was usually not OS. It was most often a more proximal disease-control or response endpoint, particularly CR, ORR, PET-negative response, or MRD-style measurement.

PFS Primary Endpoints Were Usually Defined Around Progression or Death

Among 45 PFS-primary trials, 36 defined PFS using progression/relapse or death (80.0%), 31 referenced Lugano-style lymphoma assessment (68.9%), and 19 used BICR/IRC or central review framing (42.2%).

Definition Features in PFS-Primary Trials
Progression / death definition
36 / 45
Lugano / lymphoma criteria
31 / 45
BICR / IRC / central review
19 / 45
Investigator assessment
16 / 45
OS vs PFS in Lymphoma Phase III Trials
Interpretation

PFS was not used as a vague surrogate label. In most PFS-primary trials it was anchored to progression or death, and frequently paired with lymphoma-specific response criteria or central-review language.

Executive Interpretation

In this 2024–2026 lymphoma Phase III cohort, the practical endpoint hierarchy is clear: PFS is the primary survival endpoint, OS is usually a secondary endpoint, and non-PFS primary endpoints are mainly response- or disease-control-based.

Clinical and regulatory reading

The data suggest an evidence model in which mature survival benefit remains important but is rarely used as the first decision point. Lymphoma Phase III programs appear to prioritize earlier disease-control readouts, with OS retained to contextualize long-term survival rather than to drive the primary analysis.