Late-breaking analysis reveals there isn’t a profit from high-dose chemotherapy adopted by autologous stem cell transplant (ASCT) for sufferers with mantle cell lymphoma (MCL) in remission following their preliminary therapy. The discovering is from the section 3 examine EA4151, Rituximab With or With out Stem Cell Transplant in Treating Sufferers With Minimal Residual Illness-Adverse Mantle Cell Lymphoma in First Full Remission by the ECOG-ACRIN Most cancers Analysis Group (ECOG-ACRIN). Affected person enrollment within the trial was stopped early after a deliberate interim evaluation failed to point out a distinction in general survival (OS) between the arms. The three-year OS charges had been 82.1% within the group that obtained an ASCT plus rituximab versus 82.7% with rituximab alone.
Lead researcher Timothy S. Fenske, MD, a professor of medication on the Medical School of Wisconsin, offered the outcomes of Summary LBA-6 immediately on the 66th American Society of Hematology (ASH) Annual Assembly and Exposition in San Diego. LBA-6 was featured on the ASH Official Press Program as certainly one of solely six late-breaking abstracts at this assembly.
On this interim evaluation, MCL sufferers in first full remission with undetectable minimal residual illness (MRD) didn’t profit from consolidative ASCT. Sufferers who stay MRD-positive after induction might profit from ASCT. Longer follow-up shall be necessary to substantiate these findings.”
Dr. Timothy S. Fenske, MD, Professor of Drugs, Medical School of Wisconsin
MCL is an incurable blood most cancers that tends to happen in older individuals (median age 65 years) and extra typically in males. In about 9 of each ten circumstances, it’s fast-growing and requires therapy instantly upon analysis. Traditionally, MCL was related to poor outcomes, however in recent times, outcomes have improved as simpler and focused therapies have turn into accessible. As we speak, the primary remission may be 8 to 10 years or longer.
A number of normal frontline (induction) and upkeep therapy choices exist, akin to intensive chemotherapy, immunotherapy, focused medication, and BTK inhibitors. Rituximab, a focused immunotherapy drug, is among the choices.
Moreover, for a few years, it has been widespread follow to supply sufferers underneath age 70 an ASCT-;if they’re bodily match sufficient to face up to the troublesome process, which includes high-dose chemotherapy adopted by re-infusion of the affected person’s personal blood stem cells.
“EA4151 is the primary randomized trial to review ASCT for MCL sufferers with undetectable MRD in first remission, inside an period of extremely efficient induction and upkeep regimens. The advantage of ASCT on this present period has been debated closely, as a result of the information suggesting advantage of ASCT all got here from the context of older trials and coverings,” mentioned Dr. Fenske.
Trial overview
MCL sufferers in first full remission after induction remedy had been eligible to affix the trial. It was funded by the US Nationwide Institutes of Well being’s Nationwide Most cancers Institute (NCI), and designed and applied by ECOG-ACRIN. Most cancers facilities and group hospitals participated within the trial by means of two massive NCI analysis applications: the Nationwide Medical Trials Community and the Blood and Marrow Transplant Medical Trials Community.
Between August 2017 and July 2024, 650 sufferers enrolled and underwent imaging (PET/CT), a bone marrow biopsy, and a blood draw. Blood was examined for the presence of any remaining most cancers cells utilizing the clonoSEQ® MRD check. This extremely delicate industrial minimal residual illness (MRD) assay is cleared by the US Meals and Drug Administration. The check can detect traces of residual lymphoma under the extent of that which normal imaging and blood testing can detect.
The general speculation of the examine was that sufferers who’re already in deep remission (with unfavorable PET/CT scan, bone marrow biopsy, and MRD testing) are much less more likely to profit from ASCT. These sufferers might be able to safely keep away from the dangers of the transplant process.
Trial outcomes
Most sufferers within the trial had full remission (CR) with undetectable MRD after induction remedy (516/650; 79%). These sufferers had been randomized to obtain both an ASCT adopted by 3 years of rituximab (Arm A; n=257) or 3 years of rituximab alone (Arm B; n=259).
The first endpoint was to check general survival (OS) between Arms A and B. With a median follow-up of two.7 years, 3-year OS was 82.1% in Arm A and 82.7% in Arm B.
The remaining sufferers within the trial had been both MRD+ CR or partial response (PR) (Arm C, n=49) or MRD indeterminate or PR with undetectable MRD (Arm D, n=85). They obtained ASCT plus 3-years of rituximab. The three-year OS was 81.9% in Arm C and 85.1% in Arm D.
Development-free survival (PFS) was a secondary endpoint. The three-year PFS was additionally comparable throughout arms: 76.6% in Arm A, 77.4% in Arm B, 76.9% in Arm C, and 73.4% in Arm D.
Instantly following the interim evaluation, the ECOG-ACRIN Information Security and Monitoring Committee advisable stopping affected person accrual, informing the trial individuals, and making the outcomes public. Their associated futility evaluation confirmed that the end result was more likely to be comparable when the examine reached the deliberate evaluation with complete enrollment and full data.