Final results from the Nordic Lymphoma Group’s phase II PHILEMON trial showed that a combination of ibrutinib, lenalidomide, and rituximab is active, well tolerated, and associated with high rates of molecular remission in a high-risk group of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL).
Findings from this study were presented by Mats Jerkeman, MD, at the Skane University Hospital in Sweden, at the 62nd American Society of Hematology Annual Meeting & Exposition.
Patients included in this study had MCL that was R/R to at least one rituximab-containing chemotherapy regimen. The primary endpoint was maximal overall response rate. The investigators also conducted minimal residual disease (MRD) monitoring during the follow-up period.
The induction phase of treatment consisted of lenalidomide 15 mg, ibrutinib 560 mg, and rituximab 375 mg/m2 followed by 1,400 mg on select days from cycles one through 11. Patients in complete response (CR), partial response (PR), or stable disease were given treatment during the maintenance phase until progression. The maintenance phase consisted of ibrutinib 560 mg and rituximab 1,400 mg on select days.
Across the 50 patients enrolled in the study, the median age was 69.5 years. The median number of previous regimens was two, and four patients had progressed in their disease after single-agent ibrutinib. In 11 out of 49 evaluable patients, the investigators detected a TP53 mutation.
The most common treatment-emergent adverse events of any grade included rash (24%) and fatigue (20%). Although five patients developed grade 3/4 neutropenia, hematologic toxicity was generally low grade in severity. There was one death, which the investigators attributed to possible treatment-related toxicity.
A total of 27 patients (54%) achieved a CR, and 10 patients (20%) experienced a PR. In evaluable patients with a TP53 mutation, the CR rate was 64%. Additionally, the CR rates among patients with blastoid/pleomorphic histology or Ki67 >30% were 62% and 50%, respectively.
The median progression-free survival (PFS) after the median 40-month follow-up period was 18 months (95% confidence interval [CI], 6.5-28). The median overall survival (OS) after follow-up was 47 months (95% CI, 30-64). Among 11 patients with a detectable TP53 mutation at time of relapse, the median PFS was 13 months (95% CI, 4.2-21) versus 34 months (95% CI, 8.3-60) in patients without a TP53 mutation.
Approximately 56% of the 28 patients evaluable for MRD at six months experienced molecular remission in blood, whereas 43% of these patients experienced molecular remission in bone marrow. The MRD negativity in bone marrow after 12 months was 68%. A total of two patients with TP53-mutated MCL were MRD-negative in bone marrow after 12 months.
According to a Cox regression multivariable analysis, the MCL International Prognostic Index was a significant prognostic indicator for PFS and OS with the ibrutinib, lenalidomide, and rituximab combination regimen.
The researchers noted that while “the activity in TP53-mutated MCL is lower than in unmutated disease,” the combination “regimen may still serve as an option for a bridge to an allogeneic transplantation or chimeric antigen receptor T-cell therapy in this category of patients.”