Dr Kahl on Frontline Strategies for Avoiding Autologous Transplant in MCL

“The EA4151 trial showed that if you are MRD negative, you don’t benefit from stem cell transplant. There are now 2 ways to avoid transplant, with the addition of a BTK inhibitor, or perforin MRD assessment and, if the disease is undetectable, subtract the transplant from treatment.”

Brad S. Kahl, MD, a professor of medicine and director of the Lymphoma Program in the Division of Oncology at Washington University School of Medicine, discussed 2 strategies that may allow patients with mantle cell lymphoma (MCL) to avoid autologous stem cell transplantation (ASCT).

Kahl began by explaining how, access to therapy remains an important consideration, and that if patients do not have acess to a BTK inhibitor for incorporation into a frontline regimen, clinicians could argue that ASCT may retain a role. However, findings from the phase o3 EA4151 trial (NCT03267433) provide another approach for determining whether transplant consolidation is necessary, he added.

The trial used minimal residual disease (MRD) testing at the end of initial therapy to evaluate the need for ASCT, Kahl said. He then highlighted that patients with undetectable MRD, indicating a deep and high-quality remission, were randomly assigned to receive ASCT plus maintenance rituximab (Rituxan) or maintenance rituximab without ASCT.

According to Kahl, the trial showed that patients who achieved MRD-negativity did not benefit from the addition of ASCT. Notably, in the trial, 3-year overall survival among all randomized patients (n = 516) was 82.7% with rituximab maintenance alone compared with 82.1% with ASCT plus rituximab (HR, 1.11; 95% CI, 0.71-1.74; P = .66).

The findings suggest that the depth of remission after frontline therapy can help identify patients for whom transplant would add treatment intensity and burden without improving outcomes. Maintenance rituximab alone therefore represents an appropriate post-induction strategy for this MRD-defined population.

Kahl concluded that clinicians have 2 potential methods for removing ASCT from first-line treatment. The first, strategy is incorporates a BTK inhibitor into frontline therapy, as demonstrated in phase 3 TRIANGLE trial (NCT02858258). The other is to assess MRD after initial treatment and omit ASCT if patients achieve undecteable MRD.