Patients with mantle cell lymphoma (MCL) did not demonstrate improved survival outcomes in a phase 3 study after receiving consolidative autologous hematopoietic cell transplant (auto-HCT) with Rituxan (rituximab) in their first complete remission (CR) with undetectable minimal residual disease (MRD).
Data from an analysis of the phase 3 ECOG-ACRIN EA4151/BMT-CTN 1601 trial was presented during the 2024 ASH Annual Meeting.
Between August 2017 and July 15, 2024, 650 patients were enrolled in the study. Patients who had an MRD-negative CR underwent randomization to auto-HCT plus Rituxan for three years (group A; 257 patients), or Rituxan alone for three years (group B; 259 patients). Those who had a partial response (MRD-positive or -negative) or an MRD-positive CR went onto the registration cohort (not randomly assigned) and received autoHCT plus Rituxan for three years (group C; 49 patients); those who had been deemed MRD indeterminate also had autoHCT plus Rituxan for three years (group D; 85 patients).
The primary analysis population included all randomized patients, but a treated-as-assigned analysis was also conducted because 25.3% of patients in group A and 0.8% in group B refused their assigned treatment.
The study showed that in all randomized patients, the three-year overall survival (OS) rate was 82.1% for auto-HCT plus Rituxan compared with 82.7% in the Rituxan-alone group; these rates were 86.2% versus 84.8% in the treated-as-assigned group.
“This means that the probability of detecting significant difference, even when the study is more fully read out, is highly improbable,” lead study author Dr. Timothy Fenske, a medical oncologist at Medical College of Wisconsin, said in an oral presentation during the meeting. “In this initial analysis, in the era of highly effective induction and maintenance regimens, [patients with] mantle cell lymphoma in first complete response with undetectable MRD did not benefit from consolidative autologous transplant. Longer follow-up will be important to confirm these findings.”
To be eligible for study enrollment, patients with MCL must have been between the ages of 18 and 70 years and in first remission. Rituxan-containing induction regimens were allowed and included those with BTK inhibitors.
Patients could be enrolled on the study before, during or after induction therapies. If clonal markers were present in molecular testing, patients went to post-induction restaging and submission of blood for MRD assessment; if no markers were found, they were identified as MRD indeterminate.
The primary end point was OS between the auto-HCT plus maintenance Rituxan versus maintenance Rituxan alone. Secondary measures included progression-free survival (PFS) in group A versus group B, as well as PFS in groups C and D and conversion rate of MRD-positive patients in group C to undetectable MRD following auto-HCT.
Study investigators assumed a six-year OS rate of 76% in the standard Rituxan maintenance group and targeted to detect a 10% improvement to 86% at six years when auto-HCT was added.
Survival Outcomes Among Treatment Groups
Findings from the study also showed that there was no significant difference observed in PFS outcomes between groups A and B. Three-year PFS rates in the all-randomized group were 76.6% and 77.4% for groups A and B, respectively; these rates were 81.5% and 80.4%, respectively, in the treated-as-assigned group.
When OS was measured between groups A and B comparing induction therapy intensity, it was found that the three-year OS rates were 83.0% for group A versus 86.2% for group B. In the non-intensive induction group, the three-year OS rates were 79.5% versus 72.8%, respectively.
“As we might expect, the survival appears somewhat superior in patients receiving intensive induction,” Fenske said. “However, receipt of autologous transplant was not associated with a significant improvement in overall survival regardless of induction intensity.”
OS was also evaluated in patients who were enrolled in groups C and D. Here, the three-year OS rates were 81.9% and 85.1%, respectively. Three-year PFS rates were 76.9% and 73.4%, respectively.
Study investigators conducted an exploratory analysis of the MRD-positive patients that comprised group C of posttransplant MRD status. The three-year PFS rates were similar at 100% versus 48.8%, respectively, “suggesting that MRD-positive patients may still benefit from autologous transplant,” Fenske said, and noted the small subgroup size.
Thirty-four deaths were reported on study, occurring from lymphoma (group A, 4.7%; group B, 3.5%; group C, 2.0%; group D, 2.4%), COVID-19 (5.1%; 6.6%; 2.0%; 3.5%), other (3.5%; 3.1%; 6.1%; 5.8%) and unknown causes (1.6%; 1.5%; 2.0%; N/A).
Reference
“Lack of benefit of autologous hematopoietic cell transplantation (auto-HCT) in mantle cell lymphoma (MCL) patients (pts) in first complete remission (CR) with undetectable minimal residual disease (uMRD): initial report from the ECOG-ACRIN EA4151 phase 3 randomized trial” by Dr. Timothy Fenske. Blood.
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