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Adding a targeted tablet to first-line chemotherapy gave older people with mantle cell lymphoma about two and a half more years before the disease returned, but they did not live longer.
SHINE randomised 523 people aged 65 or over with untreated mantle cell lymphoma to ibrutinib 560 mg daily until progression or unacceptable toxicity (261) or placebo (262), each with six cycles of bendamustine 90 mg per square metre and rituximab, followed by up to twelve further doses of rituximab maintenance every eight weeks in responders.
At a median follow-up of 84.7 months, median progression-free survival was 80.6 months with ibrutinib against 52.9 months with placebo (hazard ratio 0.75, 95 per cent confidence interval 0.59 to 0.96, p = 0.01). Complete response was 65.5 against 57.6 per cent (p = 0.06). Overall survival was similar in the two groups. Grade 3 or 4 adverse events during treatment occurred in 81.5 per cent against 77.3 per cent.
Twenty-eight months of extra progression-free time is a large number in a disease that is not curable with chemotherapy, and it did not translate into longer life, which is the finding that shaped what came next. The ECHO trial repeated the design with acalabrutinib, a more selective Bruton tyrosine kinase inhibitor chosen for lower toxicity, and ENRICH took the opposite route and removed the chemotherapy entirely.
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.
523 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (median)primary | Ibrutinib with bendamustine and rituximab | 261 | 80.6 months | 0.75 (0.59 to 0.96) | 0.01 | link |
| Placebo with bendamustine and rituximab | 262 | 52.9 months | ||||
| Complete response rate | Ibrutinib with bendamustine and rituximab | 261 | 65.5% | - | 0.06 | - |
| Placebo with bendamustine and rituximab | 262 | 57.6% |
A second randomised confirmation that adding a Bruton tyrosine kinase inhibitor to first-line bendamustine-rituximab delays progression in older patients with mantle cell lymphoma, with a toxicity profile that did not improve as much as the drug's selectivity promised.
The authors' conclusion is that ibrutinib-rituximab should be considered a new standard-of-care option for first-line treatment of older patients with mantle-cell lymphoma. The subgroup split means it is clearly better than R-CHOP and roughly equivalent to bendamustine-rituximab.
Twenty-eight extra months of progression-free survival, with no survival gain and a high rate of severe adverse events in both arms. It set up the two trials that followed: ECHO, which substituted a more selective inhibitor, and ENRICH, which removed the chemotherapy.
Shares Maintenance and consolidation in lymphoma: where it works and where it does not, TRIANGLE, CCND1, Maintenance therapy and the tag lymphoma-evidence.
Shares Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma, Maintenance and consolidation in lymphoma: where it works and where it does not, Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH): a randomised, open-label, phase 2/3 superiority trial, ENRICH and the tag lymphoma-evidence.
Shares TRIANGLE, CCND1, Maintenance therapy, CD20 and the tag lymphoma-evidence.
Shares Maintenance and consolidation in lymphoma: where it works and where it does not, Maintenance therapy, CD20, Rituximab and the tag lymphoma-evidence.
Shares Maintenance and consolidation in lymphoma: where it works and where it does not, Maintenance therapy, Older and multimorbid patients are excluded and undertreated, Rituximab and the tag lymphoma-evidence.
Shares B-cell receptor / BTK signalling (to NF-κB), BTK (Bruton tyrosine kinase), Older and multimorbid patients are excluded and undertreated, CD20 and the tag lymphoma-evidence.
Shares Maintenance and consolidation in lymphoma: where it works and where it does not, Maintenance therapy, Older and multimorbid patients are excluded and undertreated, Rituximab and the tag lymphoma-evidence.
Shares Maintenance and consolidation in lymphoma: where it works and where it does not, Maintenance therapy, CD20, Rituximab and the tag lymphoma-evidence.