Thiotepa-Containing Conditioning Regimens Improve Survival Outcomes in Patients With PCNSL

Thiotepa-containing conditioning regimens, including thiotepa/busulfan/cyclophosphamide (TBC) and thiotepa/carmustine (TT-BCNU), were associated with favorable survival outcomes in patients with primary diffuse large B-cell lymphoma of the central nervous system, known as PCNSL, according to results presented at the 2020 ASH Annual Meeting.

Lead study author Trent Wang, DO, of the Sylvester Comprehensive Cancer Center in Miami, Florida, presented the findings of the study, which included 608 adult patients with PCNSL enrolled in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. All patients had undergone a first hematopoietic cell transplantation (HCT) between 2010 and 2018.

Individuals were treated with the following conditioning regimens:

  • TBC (n=265)
  • TT-BCNU (n=278)
  • BEAM (BCNU/etoposide/cytarabine/melphalan; n=65)

There were no substantial differences between the TBC, TT/BCNU, and BEAM groups in terms of age at baseline (medians = 59 vs. 61 vs. 62 years, respectively; p=0.14). The treatment groups were also comparable in regard to sex, race, HCT-comorbidity index (HCT-CI), and remission status.

At one month after transplant, nearly all patients had achieved neutrophil recovery: 96% in the TBC group and 100% in both the TT-BCNU and BEAM groups.

At one year, the cumulative incidence rates of relapse were 6% with TBC, 10% with TT-BCNU, and 23% with BEAM. At three years, these rates increased to 11%, 15%, and 37%, respectively.

Rates of non-relapse mortality at 100 days and one year were significantly higher in the TBC-treated patients, compared with those who received TT-BCNU or BEAM (TABLE). However, Dr. Wang and coauthors observed significantly higher rates of survival at three years in the TBC and TT-BCNU groups, compared with those who were conditioned with BEAM.

The most common cause of death across all three cohorts was relapse of primary disease, including 38% in TBC, 72% in TT-BCNU, and 76% in BEAM. Infections (15%) and organ failure (21%) were other significant causes of death in the overall cohort.

“In this CIBMTR analysis in patients with PCNSL, we found favorable outcomes with thiotepa-containing conditioning regimens,” the researchers concluded. “Adjusted three-year progression-free survival [analysis] favored TBC and TT-BCNU over BEAM and suggest that use of BEAM should be discouraged in this specific setting.”

They added that determining whether TBC or TT-BCNU is the optimal conditioning regimen will require further inquiry in a prospective clinical trial.

Study authors report no relevant conflicts of interest.

Reference

Wang T, Scordo M, Ahn KW, et al. Superiority of thiotepa-containing conditioning regimens in patients with primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) undergoing autologous hematopoietic cell transplantation (autoHCT). Abstract #615. Presented at the 2020 American Society of Hematology Annual Meeting, December 7, 2020.