Clinical trialPhase 3Leukaemia

Follow-up from the A041202 study shows continued efficacy of ibrutinib regimens for older adults with CLL

Blood · 2024

Woyach JA, Perez Burbano G, Ruppert AS, Miller C, Heerema NA, Zhao W, et al. Blood. 2024. 143:1616-1627

Study type: Clinical trial
Study name: Alliance A041202
Phase: Phase 3
Design: Updated analysis of a three-arm randomised trial (median follow-up 55 months)
Source: Blood · 2024
Trial registration: NCT01886872

In plain words

In older people with CLL, after about 4 and a half years of follow-up, 76% of patients taking ibrutinib tablets were living without their disease getting worse, compared with 47% of patients who had the chemoimmunotherapy bendamustine-rituximab. Adding rituximab to ibrutinib gave no benefit. High blood pressure and an irregular heartbeat (atrial fibrillation) are side effects that need to be monitored.

Key results

76% (ibrutinib), 76% (IR), 47% (BR)

48-month progression-free survival

Median PFS 44 months with BR; not reached in the ibrutinib groups

No difference

Overall survival

Drugs in this study:Bendamustine Ibrutinib (Imbruvica)Rituximab (Rituxan/MabThera)

Dose and schedule cards

Ibrutinib monotherapy (A041202, RESONATE-2)

CLL/SLL requiring treatment (iwCLL), including with TP53 abnormalities; continuous treatmentCycle length: ContinuousOn the page “Leukaemia” · Regimens and dosing in CLL: continuous BTK inhibitor therapy

CLL/SLL requiring treatment (iwCLL), including with TP53 abnormalities; continuous treatment

Drug	Dose	Route	Schedule
Ibrutinib	420 mg once daily	Oral, with a glass of water	Continuous

Cycle length: Continuous
Duration: Until progression or unacceptable toxicity

Atrial fibrillation, heart failure and sudden death, hypertension (monitor blood pressure regularly) and bleeding (caution with anticoagulants and antiplatelet agents; withhold for 3 to 7 days before and after surgery depending on bleeding risk) are important adverse effects; monthly blood counts and liver function monitoring.

On the page “Leukaemia” · Regimens and dosing in CLL: continuous BTK inhibitor therapy

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

1Bendamustine + rituximab (BR)

Six 28-day cycles: bendamustine 90 mg/m² IV on days 1 and 2 of each cycle (cycle 1 dose 70 mg/m² at the investigator's discretion) + rituximab 375 mg/m² one day before day 1 of cycle 1, then 500 mg/m² on day 1 of cycles 2 to 6. On progression, crossover to ibrutinib was allowed up to 1 year after progression.

2Ibrutinib alone

Ibrutinib 420 mg orally daily until disease progression or unacceptable toxicity.

3Ibrutinib + rituximab (IR)

Ibrutinib 420 mg daily continuously (on shared days, before rituximab) + rituximab 375 mg/m² weekly for 4 weeks starting on day 1 of cycle 2, then on day 1 of cycles 3 to 6; 28-day cycles.

Source of the regimen details: Regimen of the original A041202 trial: full text of the NEJM 2018 paper in PMC (PMC6325637), Methods section

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 with untreated CLL who had an indication for treatment according to iwCLL criteria.

Endpoints

Progression-free survival, overall survival and adverse events.

Safety and side effects

Atrial fibrillation in 3% of patients in the BR group and 18% of patients receiving ibrutinib; hypertension (any grade) 27% versus 55%.

Clinical significance and place in guidelines

This follow-up confirms the durable efficacy of continuous ibrutinib in untreated CLL in older patients, including those with TP53 aberrations.

Limitations

No difference in overall survival was seen; the cardiovascular toxicity of ibrutinib is substantial.

Original article (DOI)PubMed ClinicalTrials.gov

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.