Ibrutinib Plus Lenalidomide and Rituximab Demonstrates Activity in R/R MCL

Ibrutinib (Imbruvica) plus lenalidomide (Revlimid) and rituximab (Rituxan) extended progression-free survival (PFS) in patients with relapsed/refractory mantle cell lymphoma (MCL), according to findings from the phase 2 PHILEMON trial (NCT02460276) presented during the 2024 EHA Congress.¹

Long-term follow-up data from the trial demonstrated that, at a median follow-up of 89.8 months, patients with relapsed or refractory MCL (n = 50) achieved a median PFS of 17.4 months (95% CI, 10.4-54.4; P = .13); the median PFS among patients with TP53 mutations (n = 11) was 12.8 months (95% CI, 8.4-not reached). Additionally, the overall response rate (ORR) was 86%.

“Ibrutinib, lenalidomide and rituximab is an active regimen in relapsed/refractory MCL, with [patients experiencing] a high ORR,” Elin Forsgren, PhD student in the Department of Immunology, Genetics and Pathology, Research programme: Cancer Precision Medicine, Research group Ingrid Glimelius, at Uppsala Universitet in Sweden, and coauthors wrote in a presentation of the findings.¹ “The combination also appears to be active in patients with TP53-mutated MCL, with a median PFS of [greater than] 1 year, and may serve as a bridge to CAR-T [cell therapy] or allogeneic stem cell transplantation.”

PHILEMON was a multicenter, open-label, single-arm study that enrolled patients 18 years of age or older with relapsed/refractory MCL at 10 centers in Sweden, Norway, Denmark, and Finland. Eligible patients previously received at least 1 rituximab-containing regimen, had an ECOG performance status of 3 or less, and had at least 1 site of measurable disease.^1,2

During the induction phase, all patients received 15 mg of oral lenalidomide daily on days 1 to 21 and 560 mg of oral ibrutinib daily on days 1 to 28; patients also received 375 mg/m² of intravenous rituximab on day 1 of cycle 1 followed by 1400 mg subcutaneously (or 375 mg/m² intravenously) on days 8, 15, and 22 of cycle 1, and then on day 1 of cycles 3, 5, 7, 9, and 11. Treatments in the induction phase were administered for up to 12 cycles consisting of 28 days. In the maintenance phase, patients received 560 mg of daily ibrutinib on days 1 to 56 and 1400 mg of subcutaneous rituximab on day 1 of 56-day cycles until disease progression.

The primary end point was ORR in the intention-to-treat population. Secondary end points included CR rate, duration of response, molecular remission rate, PFS, and overall survival.²

At baseline, the median age of patients enrolled in the trial was 69 years (range, 45-85) and 90% had an ECOG performance status of 1 or less. Most patients were male (72%), had Ann Arbor stage IV disease (84%), and had bone marrow involvement (68%). The median number of prior therapies received was 2 (range, 1-7) and prior lines of therapy included autologous stem-cell transplantation (42%), ibrutinib (8%), allogeneic stem-cell transplantation (6%), and lenalidomide (2%).

Two patients died related to toxicity during the study, and 73% of patients died due to MCL, which was the most common cause of death.¹

References

1. Forsgren E, Bentzen H, Riise J, et al. Ibrutinib, lenalidomide and rituximab in relapsed mantle cell lymphoma - long term follow-up of the Nordic Lymphoma Group MCL6 philemon trial.Presented at: 2024 European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract P1118.
2. Jerkeman M, Eskelund CW, Hutchings M, et al. Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. Lancet Haematol. 2018;5(3):e109-e116. doi:10.1016/S2352-3026(18)30018-8