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Fifteen months of two oral drugs cut the risk of progression by nearly 80% versus chemoimmunotherapy in older patients, and later showed a survival advantage.

PFS HR 0.216 (95% CI 0.131-0.357); uMRD in marrow 51.9% vs 17.1%; 4-year OS HR 0.487 (2023 update). NEJM Evidence 2022. EU approval of the fixed-duration regimen 2022; not FDA-approved in the US.

Setting
Previously untreated CLL, age ≥65 or with comorbidities, no del(17p)/TP53: fixed-duration ibrutinib + venetoclax vs chlorambucil + obinutuzumab
Phase
Phase 3
Sponsor
Janssen
Registry
Headline result
PFS HR 0.216; OS HR 0.487 (4-year).
Reported
2021
Enrolled
211
Replication
CAPTIVATE (single-arm, younger) and AMPLIFY (acalabrutinib-venetoclax) support BTKi + BCL2i fixed duration; FLAIR (UK, ibrutinib-venetoclax vs FCR) also positive.

Outcomes

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In plain words
What these results mean for people, not percentages
211 people took part
Progression-free survivalprimarysurrogate endpoint
  • The treated group had about 78 percent lower chance of the event at any given time (hazard ratio 0.216).
  • The absolute difference, how many more people out of 100 were helped, is not reported here.
Undetectable MRD in bone marrow at 3 months post-treatmentsurrogate endpoint
  • 51.9 vs 17.1 out of 100 had no detectable disease on sensitive tests with Ibrutinib + venetoclax compared with Chlorambucil + obinutuzumab; 34.8 more per 100.
  • Roughly one extra person helped for every 3 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
Be careful
  • This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
  • These results apply to the people the trial enrolled: Previously untreated CLL, age ≥65 or with comorbidities, no del(17p)/TP53: fixed-duration ibrutinib + venetoclax vs chlorambucil + obinutuzumab. People in a different situation may not see the same effect.
  • The trial selected people by a biomarker (17p); the result should not be assumed for people whose cancer does not have it.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

211 participants enrolled.

Progression-free survivalprimary
HR 0.216 (0.131–0.357) · p <0.0001

Numbers not yet public.

Source
Undetectable MRD in bone marrow at 3 months post-treatment
Ibrutinib + venetoclax51.9 of 100
Chlorambucil + obinutuzumab17.1 of 100
EndpointArmnValueHR (95% CI)pSource
Progression-free survivalprimaryIbrutinib + venetoclax1060.216 (0.131–0.357)<0.0001link
Chlorambucil + obinutuzumab105
Undetectable MRD in bone marrow at 3 months post-treatmentIbrutinib + venetoclax51.9%
Chlorambucil + obinutuzumab17.1%
Replication
CAPTIVATE (single-arm, younger) and AMPLIFY (acalabrutinib-venetoclax) support BTKi + BCL2i fixed duration; FLAIR (UK, ibrutinib-venetoclax vs FCR) also positive.

Key papers

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Connected

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