High-dose chemotherapy followed by autologous stem cell transplantation is ineffective in patients with mantle cell lymphoma

High-dose chemotherapy followed by autologous stem cell transplantation is ineffective in patients with mantle cell lymphoma

Current research shows that high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) provides no benefit in patients with mantle cell lymphoma (MCL) who are in remission after initial treatment. The result comes from the phase 3 study EA4151,Rituximab with or without stem cell transplantation in treating patients with minimal residual disease-negative mantle cell lymphoma in first complete remissionfrom the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN). Patient enrollment in the study was stopped early after a planned interim analysis failed to demonstrate a difference in overall survival (OS) between the arms. The 3-year OS rates were 82.1% in the group that received ASCT plus rituximab compared to 82.7% with rituximab alone.

Lead investigator Timothy S. Fenske, MD, professor of medicine at the Medical College of Wisconsin, presented the results of Abstract LBA-6 today at the 66th Annual Meeting and Exhibition of the American Society of Hematology (ASH) in San Diego. LBA-6 was presented in the official ASH press program as one of only six current 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. Patients who remain MRD positive after induction may benefit from ASCT. Longer follow-up will be important to confirm these results.”

Dr. Timothy S. Fenske, MD, Professor of Medicine, Medical College of Wisconsin

MCL is an incurable blood cancer that tends to occur in older people (average age 65 years) and more commonly in men. In about nine out of ten cases, the disease progresses rapidly and requires treatment immediately after diagnosis. Historically, MCL has been associated with poor outcomes, but in recent years outcomes have improved as more effective and targeted therapies have become available. Nowadays, the first remission can last 8 to 10 years or longer.

There are several standard options for initial treatment (induction) and maintenance therapy, such as: B. intensive chemotherapy, immunotherapy, targeted drugs and BTK inhibitors. Rituximab, a targeted immunotherapy drug, is one of the options.

In addition, it has been common practice for many years to offer ASCT to patients under the age of 70 - as long as they are physically fit enough to endure the difficult procedure that involves high-dose chemotherapy and subsequent reinfusion of the patient's own blood stem cells.

"EA4151 is the first randomized trial to evaluate ASCT in MCL patients with undetectable MRD in first remission, in an era of highly effective induction and maintenance therapies. The utility of ASCT in this current era has been hotly debated, as data suggest a benefit of ASCT all arose in the context of older trials and treatments," said Dr. Fenske.

Test overview

MCL patients who were in first complete remission after induction therapy were eligible to participate in the study. It was funded by the National Cancer Institute (NCI) of the US National Institutes of Health and designed and implemented by ECOG-ACRIN. Cancer centers and community hospitals participated in the study through two major 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 were enrolled and underwent imaging (PET/CT), bone marrow biopsy, and blood sampling. The blood was examined for the presence of residual cancer cells using the clonoSEQ® MRD test. This highly sensitive commercial Minimum Residual Disease (MRD) test is approved by the US Food and Drug Administration. The test can detect traces of residual lymphoma below the level that can be detected with standard imaging and blood tests.

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 test) are less likely to benefit from ASCT. These patients may be able to safely avoid the risks of the transplant procedure.

Test results

Most patients in the study had a complete response (CR) with undetectable MRD after induction therapy (516/650; 79%). These patients were randomized to receive either 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 the comparison of overall survival (OS) between arms A and B. At a median follow-up of 2.7 years, the 3-year OS was 82.1% in arm A and 82.7% in arm B.

The remaining patients in the study 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 in all arms: 76.6% in arm A, 77.4% in arm B, 76.9% in arm C and 73.4% in arm D.

Immediately after the interim analysis, the ECOG-ACRIN Data Safety and Monitoring Committee recommended stopping patient enrollment, informing study participants, and publishing the results. Their associated futility analysis indicated that the outcome would likely be similar if the study reached the planned analysis with full enrollment and complete information.

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