Untreated CLL
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycles 1–3 | |||
| Ibrutinib | 420 mg once daily | Oral | Continuous |
| Cycles 4–15 | |||
| Ibrutinib + venetoclax | Ibrutinib 420 mg; venetoclax with a 5-week ramp-up to 400 mg once daily | Oral | Continuous |
Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial
Niemann CU, Munir T, Moreno C, Owen C, Follows GA, Benjamini O, et al. Lancet Oncol. 2023. 24:1423-1433
- Study type
- Clinical trial
- Study name
- GLOW
- Phase
- Phase 3
- Design
- Randomised (1:1), multicentre, open-label trial at 67 centres in 14 countries; follow-up report with a median of 46 months
- Sample size
- 211 patients (106 ibrutinib-venetoclax, 105 chlorambucil-obinutuzumab)
- Source
- Lancet Oncol · 2023
- Trial registration
- NCT03462719
In plain words
In older patients or those with other illnesses, a combination of two tablets, ibrutinib and venetoclax, taken for about 15 months and then stopped, controlled the disease much better than chemotherapy combined with an antibody (chemoimmunotherapy) after about 4 years of follow-up (75% versus 25% were still free of disease progression at 42 months).
Key results
74.6% vs 24.8%
42-month progression-free survival
HR 0.214 (0.138–0.334); P<0.0001; median follow-up 46 months
15 vs 30 patients
Deaths
Post-treatment deaths from infection: 3 vs 10
Dose and schedule cards
Fixed-duration ibrutinib + venetoclax (GLOW; FLAIR with MRD-guided duration)
Untreated CLLCycle length: Every 28 daysOn the page “Blood cancers (leukaemia, lymphoma and myeloma)” · Treatment regimens and dosing in leukaemias
Fixed-duration ibrutinib + venetoclax (GLOW; FLAIR with MRD-guided duration)
Untreated CLL; in GLOW, patients aged 65 years and older, or aged 18 to 64 years with a CIRS score above 6 or CrCl below 70 mL/min, ECOG ≤2On the page “Leukaemia” · Regimens and dosing in CLL: fixed-duration targeted therapy
Untreated CLL; in GLOW, patients aged 65 years and older, or aged 18 to 64 years with a CIRS score above 6 or CrCl below 70 mL/min, ECOG ≤2
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycles 1–3 (lead-in) | |||
| Ibrutinib | 420 mg once daily | Oral | Continuous |
| Cycles 4–15 | |||
| Ibrutinib | 420 mg once daily | Oral | Continuous |
| Venetoclax | 5-week ramp-up to 400 mg once daily | Oral, with food | Continuous |
The doses are from the GLOW abstract; in FLAIR, treatment duration was guided by MRD monitoring, and the details are in the full text of the paper. This combination is not in the US FDA label.
On the page “Leukaemia” · Regimens and dosing in CLL: fixed-duration targeted therapy
CLDN18.2-positive adenocarcinoma: zolbetuximab + mFOLFOX6 or CAPOX (SPOTLIGHT and GLOW)
Advanced HER2-negative, CLDN18.2-positive adenocarcinoma (moderate to strong staining in 75% or more of tumour cells); FDA label in gastric and gastroesophageal junction tumours; particularly with PD-L1 below 1Each drug’s schedule in the tableOn the page “Oesophageal cancer” · Advanced or metastatic disease, first-line: adenocarcinoma
Advanced HER2-negative, CLDN18.2-positive adenocarcinoma (moderate to strong staining in 75% or more of tumour cells); FDA label in gastric and gastroesophageal junction tumours; particularly with PD-L1 below 1
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Zolbetuximab | First dose 800 mg/m²; then 600 mg/m² every 3 weeks or 400 mg/m² every 2 weeks | IV, before chemotherapy | First dose on Day 1; then every 3 weeks or every 2 weeks, depending on the dose |
| With one of two regimens | |||
| mFOLFOX6 | Oxaliplatin 85, leucovorin 400, fluorouracil 400 bolus and 2400 mg/m² continuous infusion | IV | Every 2 weeks (up to 12 treatments) |
| CAPOX | Oxaliplatin 130 mg/m² on Day 1 (up to 8 cycles) + capecitabine 1000 mg/m² twice daily on Days 1–14 | IV / oral | Every 3 weeks |
Doses from the zolbetuximab FDA label and the ASCO guideline. Premedication with a combination of antiemetics (an NK-1 and/or 5-HT3 receptor antagonist) is required before each infusion; the infusion is started at a slow rate, and dose reduction is not recommended.
On the page “Oesophageal cancer” · Advanced or metastatic disease, first-line: adenocarcinoma
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Treatment arms and regimens
1Ibrutinib + venetoclax (fixed duration)
Three cycles of ibrutinib 420 mg daily orally alone, then 12 cycles of ibrutinib plus venetoclax 400 mg daily orally (with dose ramp-up over 5 weeks).
2Chlorambucil + obinutuzumab
Six cycles of chlorambucil 0.5 mg/kg orally on days 1 and 15 of each cycle, and obinutuzumab 1000 mg IV on days 1 (or 100 mg on day 1 and 900 mg on day 2), 8 and 15 of cycle 1 and on day 1 of cycles 2 to 6.
Source of the regimen details: Abstract of the paper (Lancet Oncol 2023)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients aged 65 years or older, or aged 18 to 64 years with a CIRS score above 6 or creatinine clearance below 70 mL/min (or both), with previously untreated chronic lymphocytic leukaemia and an ECOG performance status of 2 or lower.
Endpoints
Primary endpoint: progression-free survival in the intention-to-treat population, assessed by an independent review committee.
Safety and side effects
After the primary analysis, one case of myelodysplastic syndrome was reported in the chlorambucil-obinutuzumab group. Treatment-related deaths occurred in one patient in the ibrutinib-venetoclax group (cardiac failure, pneumonia and sinus node dysfunction) and one patient in the chlorambucil-obinutuzumab group (pneumonia).
Clinical significance and place in guidelines
This four-year follow-up confirms the durable benefit of all-oral, fixed-duration ibrutinib-venetoclax in older patients or those with comorbidities.
Limitations
Open-label trial with a relatively small sample size; the comparator was chemoimmunotherapy rather than another targeted therapy.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.