Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation

Abstract

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

Fig 1.

Graphs of (A) overall survival and (B) progression-free survival after autologous stem-cell transplantation in patients with DEL compared with patients without DEL. DEL, double-expressor lymphoma.

Fig 2.

Graphs of overall survival and progression-free survival after autologous stem-cell transplantation in patients with DHL compared with patients without DHL. (A) Overall survival. (B) Progression-free survival. (C) Progression-free survival in patients with DHL compared with patients with DEL without DHL and patients with neither DEL nor DHL. (D). Progression-free survival curves adjusted for baseline covariates, stratifying patients by disease status into nonDEL/nonDHL (n = 58), DEL/nonDHL (n = 47), nonDEL/DHL (n = 7), and DEL/DHL (n = 5). DEL, double-expressor lymphoma; DHL, double-hit lymphoma.

Fig A1.

Flowchart of patient enrollment in this study. ASCT, autologous stem-cell transplantation; auto-allo, autologous-allogeneic; BCL-U, unclassifiable B-cell lymphoma with features intermediate between Burkitt lymphoma and DLBCL; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; FISH, fluorescence in situ hybridization; FNA, fine-needle aspiration; IHC, immunohistochemistry; NHL, non-Hodgkin lymphoma; PCNSL, primary CNS lymphoma; PMBCL, primary mediastinal B-cell lymphoma; PTLD, post-transplant lymphoproliferative disease.