Poorer Outcomes Reported After ASCT in Double-Hit and Double-Expressor Relapsed and Refractory Lymphomas
Patients with double-hit and double-expressor relapsed/refractory diffuse large B-cell lymphomas have poorer outcomes after autologous stem cell transplantation (ASCT), according to the findings of a retrospective analysis reported by Herrera et al in the Journal of Clinical Oncology.
Double-hit lymphomas are diffuse large B-cell lymphomas with concurrent chromosomal rearrangements involving MYC and BCL2 or BCL6 genes. Double-expressor lymphomas are diffuse large B-cell lymphomas with co-expression of MYC and BCL2 proteins on immunohistochemistry.
Study Details
The analysis included 117 patients with chemotherapy-sensitive relapsed/refractory diffuse large B-cell lymphomas who underwent ASCT at Dana-Farber Cancer Institute/Brigham and Women’s Hospital or City of Hope National Medical Center and who had available archival tumor material. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization for MYC were performed. Fluorescence in situ hybridization for BCL2 and BCL6 was also performed in cases with MYC rearrangement or copy gain.
Survival Outcomes
Overall, 44% of patients had double-expressor lymphoma and 10% had double-hit lymphoma. Progression-free survival at 4 years was 48% in patients with double-expressor lymphoma vs 59% in those with non–double-expressor lymphoma (P = .049), and 4-year overall survival was 56% vs 67% (P = .10). Progression-free survival at 4 years was 28% in patients with double-hit lymphoma vs 57% in those with non–double-hit lymphoma (P = .013), and 4-year overall survival was 25% vs 61% (P = .002). Among the 4% of patients with concurrent double-expressor and double-hit lymphomas, 4-year progression-free survival was 0%.
In multivariate analysis, factors significantly associated with progression-free survival were double-expressor (hazard ratio [HR] = 1.8, P = .035) and double-hit lymphomas (HR = 2.9, P = .009). Factors significantly associated with overall survival were double-hit lymphoma (HR = 3.4, P = .004) and remission status at ASCT (HR for partial vs complete response = 2.4, P = .007).
The investigators concluded: “[Double-expressor lymphoma] and [double-hit lymphoma] are both associated with inferior outcomes after ASCT in patients with [relapsed/refractory diffuse large B-cell lymphoma]. Although ASCT remains a potentially curative approach, these patients, particularly those with [double-hit lymphoma], are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.”
The study was supported by a Conquer Cancer Foundation/ASCO Young Investigator Award, National Cancer Institute grants, Dana-Farber Cancer Institute Award Fund for Collaborative Research Initiatives in Hematologic Oncology, and Harold and Virginia Lash/David Lash Fund for Lymphoma Research.
Philippe Armand, MD, PhD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
