A large-scale phase 3 clinical trial is underway to determine whether autologous hematopoietic cell transplantation (auto-HCT) remains beneficial for patients with mantle cell lymphoma (MCL) in the context of modern treatment approaches.
Dr. Timothy S. Fenske, section head of Hematologic Malignancies in the Division of Hematology/Oncology at the Medical College of Wisconsin, recently discussed the rationale behind the ECOG-ACRIN EA4151 trial (NCT-3267433), which is examining the continued role of auto-HCT in MCL treatment.
"We undertook this study, ECOG-ACRIN EA4151, to explore whether the autologous transplant does still offer benefit [to patients] in the current [MCL] treatment era," Dr. Fenske explained.
Evolving Treatment Landscape for MCL
Historically, patients with MCL have typically undergone auto-HCT after achieving complete remission (CR) with first-line therapy. However, as Dr. Fenske noted, recent advances in first-line treatment options have prompted clinicians to question whether this intensive procedure remains necessary.
This reassessment follows results from the phase 3 TRIANGLE trial (NCT02858258), which demonstrated that auto-HCT provided no additional benefit when used alongside induction and maintenance therapy regimens containing rituximab (Rituxan), ibrutinib (Imbruvica), and high-dose cytarabine in MCL patients.
Study Design and Patient Population
The ECOG-ACRIN EA4151 trial was specifically designed to address whether auto-HCT continues to benefit patients in the context of contemporary treatment approaches. The study enrolled patients with MCL who achieved first deep complete remission with frontline rituximab-containing induction therapy, as measured by minimal residual disease (MRD) assay.
A total of 650 patients were assigned to one of four treatment arms:
- Arm A (n = 257): Auto-HCT plus rituximab in patients with MRD-negative CR
- Arm B (n = 259): Rituximab alone in patients with MRD-negative CR
- Arm C (n = 49): Auto-HCT plus rituximab in patients with partial response or MRD-positive CR
- Arm D (n = 85): Auto-HCT plus rituximab in patients with indeterminate MRD status
Primary and Secondary Endpoints
The trial designated overall survival as its primary endpoint, with progression-free survival and undetectable MRD conversion rates serving as key secondary endpoints. This comprehensive approach will help researchers determine whether the intensive auto-HCT procedure provides meaningful clinical benefit compared to less intensive approaches in the current treatment landscape.
Clinical Implications
The results of this trial could significantly impact standard treatment protocols for MCL patients. If auto-HCT is found to provide no additional benefit over rituximab alone in patients achieving MRD-negative complete remission, treatment guidelines may shift toward less intensive approaches, potentially reducing treatment-related morbidity while maintaining efficacy.
Conversely, if auto-HCT demonstrates superior outcomes in specific patient subgroups, the findings could help clinicians better identify which MCL patients are most likely to benefit from transplantation in the modern treatment era.
The study represents an important step in optimizing MCL treatment strategies, particularly as the therapeutic landscape continues to evolve with the introduction of novel targeted agents and combination regimens.
MCL Treatment Context
Mantle cell lymphoma is a rare and aggressive form of non-Hodgkin lymphoma that accounts for approximately 6% of all NHL cases. The disease typically affects older adults, with a median age at diagnosis of 68 years, and has historically been challenging to treat, with frequent relapses despite intensive therapy.
Recent years have seen significant advances in MCL treatment, including the approval of BTK inhibitors like ibrutinib, targeted therapies, and novel combination approaches. These developments have prompted researchers to reevaluate established treatment paradigms, including the role of auto-HCT as consolidation therapy.
The findings from ECOG-ACRIN EA4151 will provide valuable evidence to guide treatment decisions in this rapidly evolving therapeutic landscape, potentially sparing some patients from unnecessary intensive procedures while ensuring others receive optimal therapy for their disease.
