Clinical trialLymphoma

Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma.

N Engl J Med · 2022523 patients (261 ibrutinib, 262 placebo)

Wang ML, Jurczak W, Jerkeman M, et al. N Engl J Med. 2022. 386:2482-2494

Study type: Clinical trial
Study name: SHINE
Design: Randomised placebo-controlled trial
Sample size: 523 patients (261 ibrutinib, 262 placebo)
Source: N Engl J Med · 2022
Trial registration: NCT01776840

In plain words

Mantle cell lymphoma in older people is usually treated with bendamustine and rituximab, followed by maintenance rituximab infusions. In this study, adding ibrutinib tablets (a targeted drug taken by mouth) to this treatment lengthened the time without the disease getting worse from about 53 months to about 81 months on average, but people in the two groups lived for a similar length of time, and severe side effects were slightly more common. Choosing this treatment should be done with your doctor, weighing the benefits against the side effects.

Key results

80.6 months vs 52.9 months

Median progression-free survival

HR 0.75 (95% CI 0.59 to 0.96); P = 0.01; median follow-up 84.7 months

65.5% vs 57.6%

Complete response

P = 0.06

Similar in the two groups

Overall survival

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

Dose and schedule cards

Ibrutinib + BR and rituximab maintenance (SHINE trial)

Previously untreated mantle cell lymphoma in patients aged 65 years and olderEach drug’s schedule in the tableOn the page “Lymphoma” · Treatment regimens and dosing: mantle cell lymphoma

Previously untreated mantle cell lymphoma in patients aged 65 years and older

Drug	Dose	Route	Schedule
Ibrutinib	560 mg once daily	Oral	Continuous
Bendamustine	90 mg/m²	IV	Days 1 and 2, every 28 days (6 cycles)
Rituximab	375 mg/m²	IV	Every 28 days (6 cycles)
Maintenance (complete or partial response)
Rituximab	375 mg/m²	IV	Every 8 weeks for up to 12 doses

Cycle schedule: BR every 28 days (6 cycles); ibrutinib daily and continuously; rituximab maintenance every 8 weeks
Duration: Ibrutinib until progression or unacceptable toxicity; 6 cycles of BR; rituximab maintenance up to 12 doses

Doses from the SHINE abstract; the BR schedule (Days 1 and 2 every 28 days) follows the standard regimen.

On the page “Lymphoma” · Treatment regimens and dosing: mantle cell lymphoma

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 + BR

Ibrutinib 560 mg orally once daily until disease progression or unacceptable toxicity, plus six cycles of bendamustine 90 mg/m² and rituximab 375 mg/m². Patients with an objective response (complete or partial): maintenance rituximab every 8 weeks for up to 12 additional doses. Dosing days within each cycle are in the full text.

2Placebo + BR

Placebo instead of ibrutinib, plus the same six cycles of bendamustine 90 mg/m² and rituximab 375 mg/m², and maintenance rituximab every 8 weeks for up to 12 additional doses in responders.

Source of the regimen details: Abstract of the paper in PubMed

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 mantle cell lymphoma.

Endpoints

Primary outcome: investigator-assessed progression-free survival.

Other outcomes: overall survival and safety.

Safety and side effects

Grade 3 or 4 adverse events during treatment occurred in 81.5% of the ibrutinib group and 77.3% of the placebo group. The safety profile of the combination was consistent with the known profiles of the individual drugs.

Clinical significance and place in guidelines

SHINE showed that adding ibrutinib to bendamustine-rituximab and maintenance rituximab in patients aged 65 years or older with untreated mantle cell lymphoma increases progression-free survival by about 2 years (median), with no difference in overall survival and slightly more grade 3 or 4 adverse events. The lack of an overall survival benefit makes the decision an individual one.

Limitations

Overall survival did not differ; the difference in complete response was not statistically significant (P = 0.06); grade 3 or 4 adverse events were slightly more frequent in the ibrutinib group; the results apply only to patients aged 65 years or older.

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.