MRD Indicates Relapse for Patients With Classical HL After ASCT

Minimal residual disease (MRD) can predict which patients with classical Hodgkin lymphoma (HL) will relapse after autologous stem cell transplantation (ASCT).

Minimal residual disease (MRD) could be used to predict which patients with classical Hodgkin lymphoma (cHL) will relapse after autologous stem cell transplantation (ASCT), according to an abstract presented at the 63rd American Society of Hematology Annual Meeting & Exposition.

A subset of patients may be cured with ASCT, but for patients with high-risk clinical features, post-ASCT maintenance therapy with brentuximab vedotin (BV) improves progression-free survival (PFS) and PD-1 blockage is being investigated as well.

The researchers analyzed patients with cHL who had serial peripheral blood mononuclear cell (PBMC) and plasma samples collected before or after ASCT to determine if minimal residual disease (MRD) could predict patients who will relapse after ASCT.

Samples from 36 patients were analyzed with 28 patients undergoing ASCT between 2014 and 2016 and 8 patients undergoing ASCT between 2015 and 2016. The 8 patients also participated in a multicenter phase 2 trial of post-ASCT pembrolizumab maintenance. The researchers quantified MRD using immunoglobulin-based next-generation sequencing (IgNGS).

The patients received a median of 2 lines of therapy and 83% had achieved a complete response with positron emission tomography (PET) before ASCT. After ASCT, 8 patients received pembrolizumab maintenance, 5 received radiation therapy, 4 received BV maintenance and 2 received allogeneic stem cell transplantation. There was a median follow-up of 50 months.

A third (33%) of patients had an identifiable clonotype and patients younger than 32 or with primary refractory disease had higher rates of clonotype detection. The 12 patients with an identifiable clonotype had a median of 4 post-ASCT plasma and 3 post-ASCT PBMC samples.

Of the 4 patients who relapsed, 3 had MRD detected within plasma samples. All of the patients with detectable MRD in their post-ASCT plasma sample relapsed and only 1 patient without detectable MRD relapsed. While 2 PBMC samples had detectable MRD, they were both from a patient who did not relapse.

Of the 3 patients with a pre-ASCT plasma sample collected with post-salvage PET scans, 1 patient had undetectable MRD after receiving pembrolizumab following progressive disease after 4 cycles of bendamustine and BV. The 2 other patients were MRD negative after salvage chemotherapy and remained in remission after ASCT.

The authors noted that clonotype detection was considerably lower among the patients studied compared with patients with other B-cell lymphomas.

“Novel MRD techniques for cHL should be investigated,” they wrote. “In this pilot study, among pts with a detectable clonotype, MRD was a dynamic marker of response to different therapies and was a specific indicator of impending relapse, suggesting that additional studies of MRD in cHL are warranted.”

Reference

Taranto E, Redd RA, Jeter E, et al. Prognostic value of minimal residual disease (MRD) among patients with classical Hodgkin lymphoma undergoing autologous stem cell transplantation. Presented at: 63rd American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, Georgia. Abstract 3491.