Ibrutinib+ BR/R-CHOP In Previously Treated FL/MZL Patients

International clinical practice guidelines recommend chemoimmunotherapy (CIT), such as bendamustine and rituximab (BR) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), for patients (pts) dealing with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Despite these recommendations, the prognosis remains bleak, especially after multiple rounds of therapy. There is an ongoing need for more effective treatments.

The SELENE study, a double-blind phase 3 trial, aimed to assess whether the addition of ibrutinib to BR or R-CHOP could extend progression-free survival (PFS) in pts with R/R FL or MZL who had previously been treated with a CIT regimen containing an anti-CD20 agent.

Adult pts diagnosed with FL or MZL who had undergone at least one previous course of CIT were subjected to randomization in a 1:1 ratio. They were then assigned to receive either 6 cycles of BR or R-CHOP, in addition to a daily dose of ibrutinib (560 mg) or a placebo. This treatment regimen was maintained until the point of progressive disease or the occurrence of unacceptable toxicity. 

The primary outcome measure was investigator-assessed PFS. Secondary endpoints encompassed overall survival (OS), overall response rate (ORR), complete response (CR) rate, duration of response (DOR), and safety.

In this study, 403 pts were included, with 347 having FL and 56 having MZL. They were randomly assigned to two groups: one receiving ibrutinib alongside CIT consisting of either BR or R-CHOP (n = 202), and the other receiving placebo with CIT (n = 201). Most pts (90.3%) were treated with BR as the background CIT regimen. Following a median follow-up period of 84 months, the median PFS was 40.5 months for the ibrutinib + CIT group, compared to 23.8 months for the placebo + CIT group (hazard ratio [HR] of 0.806 with a 95% confidence interval [CI] of 0.626–1.037; p = 0.0922). 

For pts with MZL, the median PFS was not determined for the ibrutinib + CIT group, while it was 91.6 months for the placebo + CIT group (HR [95% CI] of 0.725 [0.312–1.682]; p = 0.451). The ORR was 91.6% for the ibrutinib + CIT group and 90.5% for the placebo + CIT group, with a complete response (CR) rate of 55.0% for the ibrutinib + CIT group and 50.2% for the placebo + CIT group. The median DOR was 44.3 months (95% CI, 32.9–60.0) for the ibrutinib + CIT group and 21.7 months (95% CI, 17.6–32.4) for the placebo + CIT group. Median OS was not reached in either group (HR [95% CI] of 0.980 [0.686–1.400]; p = 0.9115). 

Regarding treatment-related adverse events (TEAEs) of grade ≥3, they were reported in 85.6% of pts in the ibrutinib + CIT group and 75.4% in the placebo + CIT group. Both groups had thirteen pts who experienced a TEAE that led to death.

The incorporation of ibrutinib into CIT demonstrated clinical effectiveness in pts with relapsed/refractory FL or MZL, as evidenced by a median PFS of 40 months for the ibrutinib + CIT group compared to 24 months for the placebo + CIT group. However, it’s important to note that the observed improvement in PFS did not achieve statistical significance. 

No new safety concerns were identified. Although the combination of ibrutinib with CIT did lead to additional toxicity, it did not adversely affect overall survival. Further analyses are warranted to investigate whether specific subgroups of FL/MZL pts may benefit from extended ibrutinib treatment following CIT.

Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3196_LBA2

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT01974440

Nastoupil, L.J., Hess, G., Pavlovsky, M.A., Danielewicz, I., Freeman, J., García-Sancho, A.M., Glazunova, V., Grigg, A., Hou, J., Janssens, A., Kim, S.J., Masliak, Z., McKay, P., Merli, F., Munakata, W., Nagai, H., Özcan, M., Preis, M., Wang, T., Zhu, J., Rowe, M., Qin, R., Henninger, T., Curtis, M., Caces, D.B., Thieblemont, C. and Salles, G. (2023), IBRUTINIB PLUS BR OR R-CHOP IN PREVIOUSLY TREATED PATIENTS WITH FOLLICULAR OR MARGINAL ZONE LYMPHOMA: THE PHASE 3 SELENE STUDY. Hematological Oncology, 41: 872-874. https://doi.org/10.1002/hon.3196_LBA2