image: Timothy S. Fenske, MD led ECOG-ACRIN EA4151, the first randomized trial to compare treatment with or without stem cell transplant in patients with MRD-negative mantle cell lymphoma in first complete remission.
Credit: Medical College of Wisconsin
Late-breaking research reveals there is no benefit from high-dose chemotherapy followed by autologous stem cell transplant (ASCT) for patients with mantle cell lymphoma (MCL) in remission following their initial treatment. The finding is from the phase 3 study EA4151, Rituximab With or Without Stem Cell Transplant in Treating Patients With Minimal Residual Disease-Negative Mantle Cell Lymphoma in First Complete Remission by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN). Patient enrollment in the trial was stopped early after a planned interim analysis failed to show a difference in overall survival (OS) between the arms. The 3-year OS rates were 82.1% in the group that received an ASCT plus rituximab versus 82.7% with rituximab alone.
Lead researcher Timothy S. Fenske, MD, a professor of medicine at the Medical College of Wisconsin, presented the results of Abstract LBA-6 today at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego. LBA-6 was featured on the ASH Official Press Program as one of only six late-breaking abstracts at this meeting.
“In this interim analysis, MCL patients in first complete remission with undetectable minimal residual disease (MRD) did not benefit from consolidative ASCT,” said Dr. Fenske. “Patients who remain MRD-positive after induction may benefit from ASCT. Longer follow-up will be important to confirm these findings.”
MCL is an incurable blood cancer that tends to occur in older people (median age 65 years) and more often in men. In about nine of every ten cases, it is fast-growing and requires treatment immediately upon diagnosis. Historically, MCL was associated with poor outcomes, but in recent years, outcomes have improved as more effective and targeted therapies have become available. Today, the first remission can be 8 to 10 years or longer.
Several standard frontline (induction) and maintenance treatment options exist, such as intensive chemotherapy, immunotherapy, targeted drugs, and BTK inhibitors. Rituximab, a targeted immunotherapy drug, is one of the options.
Additionally, for many years, it has been common practice to offer patients under age 70 an ASCT—if they are physically fit enough to withstand the difficult procedure, which involves high-dose chemotherapy followed by re-infusion of the patient’s own blood stem cells.
“EA4151 is the first randomized trial to study ASCT for MCL patients with undetectable MRD in first remission, within an era of highly effective induction and maintenance regimens. The benefit of ASCT in this current era has been debated heavily, because the data suggesting benefit of ASCT all came from the context of older trials and treatments,” said Dr. Fenske.
Trial Overview
MCL patients in first complete remission after induction therapy were eligible to join the trial. It was funded by the US National Institutes of Health’s National Cancer Institute (NCI), and designed and implemented by ECOG-ACRIN. Cancer centers and community hospitals participated in the trial through two large NCI research programs: the National Clinical Trials Network and the Blood and Marrow Transplant Clinical Trials Network.
Between August 2017 and July 2024, 650 patients enrolled and underwent imaging (PET/CT), a bone marrow biopsy, and a blood draw. Blood was tested for the presence of any remaining cancer cells using the clonoSEQ® MRD test. This highly sensitive commercial minimal residual disease (MRD) assay is cleared by the US Food and Drug Administration. The test can detect traces of residual lymphoma below the level of that which standard imaging and blood testing can detect.
The overall hypothesis of the study was that patients who are already in deep remission (with negative PET/CT scan, bone marrow biopsy, and MRD testing) are less likely to benefit from ASCT. These patients may be able to safely avoid the risks of the transplant procedure.
Trial Results
Most patients in the trial had complete remission (CR) with undetectable MRD after induction therapy (516/650; 79%). These patients were randomized to receive either an ASCT followed by 3 years of rituximab (Arm A; n=257) or 3 years of rituximab alone (Arm B; n=259).
The primary endpoint was to compare overall survival (OS) between Arms A and B. With a median follow-up of 2.7 years, 3-year OS was 82.1% in Arm A and 82.7% in Arm B.
The remaining patients in the trial were either MRD+ CR or partial response (PR) (Arm C, n=49) or MRD indeterminate or PR with undetectable MRD (Arm D, n=85). They received ASCT plus 3-years of rituximab. The 3-year OS was 81.9% in Arm C and 85.1% in Arm D.
Progression-free survival (PFS) was a secondary endpoint. The 3-year PFS was also similar across arms: 76.6% in Arm A, 77.4% in Arm B, 76.9% in Arm C, and 73.4% in Arm D.
Immediately following the interim analysis, the ECOG-ACRIN Data Safety and Monitoring Committee recommended stopping patient accrual, informing the trial participants, and making the results public. Their related futility analysis showed that the outcome was likely to be similar when the study reached the planned analysis with total enrollment and complete information.
Abstract LBA-6 is publicly available on the ASH website. The ClinicalTrials.gov record is NCT03267433.
About ECOG-ACRIN
The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) is a membership-based scientific organization known for advancing precision medicine and biomarker research through its leadership of major national clinical trials that integrate cutting-edge genomic approaches. Nearly 21,000 member researchers and advocates from approximately 1,400 cancer centers and community hospitals collaborate across ECOG-ACRIN’s nearly 40 scientific committees to design studies spanning the cancer care spectrum, from early detection to management of advanced disease. ECOG-ACRIN is funded primarily by the National Cancer Institute (NCI), part of the National Institutes of Health. To learn more, visit www.ecog-acrin.org and follow us on X/Twitter @EAonc, Facebook, LinkedIn, YouTube, and Instagram.
Method of Research
Randomized controlled/clinical trial
Subject of Research
People