KEY TAKEAWAYS
- The phase 2 clinical trial aimed to evaluate progression-free survival in elderly patients with untreated mantle-cell lymphoma receiving Ibrutinib in combination with bendamustine and rituximab.
- A randomized assignment was done where patients aged 65 or older received either ibrutinib or a placebo, along with six cycles of bendamustine and rituximab.
- The trial’s outcome was that administering Ibrutinib in combination with conventional chemoimmunotherapy resulted in a substantial extension of progression-free survival.
- The study involved 523 patients, with 261 patients in the ibrutinib group and 262 in the placebo group.
- The researchers concluded that administering the Ibrutinib combo extends progression-free survival with a manageable safety profile.
The administration of Ibrutinib, a potent inhibitor of Bruton’s tyrosine kinase, in combination with bendamustine and rituximab, followed by rituximab maintenance therapy, may confer clinical benefit to elderly patients with untreated mantle-cell lymphoma. The study involved a randomized assignment of patients aged 65 or older to receive either ibrutinib (560 mg, orally administered once daily until disease progression or unacceptable toxic effects) or placebo, in addition to six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients who exhibited an objective response, including complete or partial response, were prescribed rituximab maintenance therapy. The therapy was administered at an interval of 8 weeks for a maximum of 12 additional doses. The principal objective was to evaluate the progression-free survival, as determined by the investigators. Survival rate and safety were assessed as well. In a randomized clinical trial, 523 patients were enrolled and allocated into two groups.
Specifically, 261 patients were assigned to the ibrutinib group, while the remaining 262 patients were assigned to the placebo group. Upon a median follow-up of 84.7 months, the ibrutinib group exhibited a median progression-free survival of 80.6 months, whereas the placebo group demonstrated a median progression-free survival of 52.9 months. The hazard ratio for disease progression or death was 0.75 with a 95% confidence interval of 0.59 to 0.96 and a P=0.01. The proportion of patients exhibiting a comprehensive response was 65.5% in the cohort treated with ibrutinib, while the placebo cohort had a response rate of 57.6% (P = 0.06). The overall survival rate exhibited no significant difference between the two groups. The frequency of grade 3 or 4 unfortunate occurrences during therapy was 81.5% in the cohort receiving ibrutinib and 77.3% in the placebo cohort. The administration of Ibrutinib in conjunction with conventional chemoimmunotherapy resulted in a substantial extension of progression-free survival. The safety profile of the combined therapy was by the established safety profiles of the individual drugs.
Source:https://pubmed.ncbi.nlm.nih.gov/35657079/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT01776840
Wang ML, Jurczak W, Jerkeman M, Trotman J, Zinzani PL, Belada D, Boccomini C, Flinn IW, Giri P, Goy A, Hamlin PA, Hermine O, Hernández-Rivas JÁ, Hong X, Kim SJ, Lewis D, Mishima Y, Özcan M, Perini GF, Pocock C, Song Y, Spurgeon SE, Storring JM, Walewski J, Zhu J, Qin R, Henninger T, Deshpande S, Howes A, Le Gouill S, Dreyling M; SHINE Investigators. Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma. N Engl J Med. 2022 Jun 30;386(26):2482-2494. doi: 10.1056/NEJMoa2201817. Epub 2022 Jun 3. PMID: 35657079.
