Timothy S. Fenske, MD, on Lack of Benefit of Autologous Hematopoietic Cell Transplantation in Mantle Cell Lymphoma Patients in First Complete Remission With Undetectable Minimal Residual Disease

Mantle cell lymphoma is a type of B-cell non-Hodgkin lymphoma for which autologous stem cell transplantation has been used as part of first-line therapy for many years. However, in recent years, it has become debatable whether the auto transplant still offers benefit for these patients. In the context of our improved first-line therapy options that we now have in this trial, ECOG 4151, we focused on mantle cell lymphoma patients in first complete remission, and we specifically focused on patients who were in a deep first remission as measured by a highly sensitive, minimal residual disease assay called the clonoSEQ assay, which is sensitive down to one in a million cells. The idea being that patients who are already in a very deep first remission may not benefit as much from the autologous transplant. If they had undetectable MRD in first remission, those patients were randomized one-to-one to either an auto stem cell transplant, followed by three years of rituximab maintenance or arm B, which was just rituximab maintenance alone, so omission of the auto stem cell transplant. Patients who were MRD positive were enrolled in arm C and they received transplant and rituximab. And then there was a fourth arm, arm D, comparing patients whose MRD status was indeterminate. So the main findings of the study were that comparing the two randomized arms, there was no significant difference in terms of overall survival or progression-free survival. And this was true whether we looked at subgroups of high risk versus low risk patients using the MIPI-c score or whether patients received intensive induction or non-intensive induction. Our conclusion is that in the current treatment landscape, it does not appear that autologous transplant offers benefit across the board to patients who are in a deep first remission. Specifically with undetectable MRD, we did an exploratory analysis on arm C, the MRD positive patients, and while there was only 49 patients in that arm, there was an interesting observation that the patients who converted from MRD positive to MRD negative after transplant did appear to have significantly improved outcomes compared to those who did not convert to MRD negativity. So overall, it appears that in our current treatment era, patients in a deep first remission with mantle cell lymphoma do not appear to benefit from autologous stem cell transplant. Those patients who remain MRD positive after induction may benefit from autologous transplant, so one might still offering transplant to those patients. Combined with the recently published TRIANGLE study from Europe, I think that our study will provide physicians and patients reassurance that autologous transplant does not need to be routinely offered to patients. This is particularly important considering that many mantle cell lymphoma patients are in their mid to late sixties or older and experience significant toxicity with the autologous stem cell transplant. So being able to avoid that in many patients I think will be an important step forward.