Thiotepa Conditioning Regimens Improve Survival in Primary Central Nervous System Lymphoma

Thiotepa-based therapies appeared to improve survival compared to treatment with carmustine, etoposide, cytarabine, and melphalan (BEAM) prior to autologous hematopoietic stem cell transplantation (AHCT) in patients with primary central nervous system lymphoma (PCNSL), data recently published in JAMA showed Oncology.

“Extrapolated from experience with systemic lymphoma, early AHCT studies for PCNSL used carmustine / etoposide / cytarabine / melphalan (BEAM) conditioning with disappointing disease control and survival results,” wrote Dr. Michael Scordo of the Memorial Sloan Kettering Cancer Center and colleagues. “More recently, phase 2 single-arm studies demonstrated sustained disease control and survival with central nervous system penetration conditioning regimens such as thiotepa / busulfan / cyclophosphamide (TBC) and thiotepa / carmustine (TT-BCNU).”

Scordo and colleagues conducted an observational cohort study of patients with primary central nervous system lymphoma who received the three most common conditioning regimens: thiotepa / busulfan / cyclophosphamide (TBC), thiotepa / carmustine (TT-BCNU), and BEAM. The researchers conducted their study on data from 603 adults enrolled in the registry of the Center for International Blood and Market Transplant Research. All patients had a stem cell transplant between January 2010 and December 2018.

Scordo and colleagues excluded patients who received unusual conditioning regimens and patients who had not fully or partially remitted prior to stem cell transplantation, as well as patients with HIV, non-Hodgkin lymphoma subtypes other than diffuse large B-cell lymphoma, and such with systemic non-Hodgkin lymphoma. The main outcome was progression-free survival (PFS). Secondary endpoints were overall survival (OS), mortality without relapse, relapse frequency, and haematopoietic recovery.

The patients had a mean age of 57 years (range 19-77) and most were men (53%). Those who received TBC and TT-BCNU had 3-year adjusted PFS rates of 75% and 76%, respectively, compared to 58% in those who received BEAM (P = 0.03). The researchers contributed this survival difference to a significantly higher risk of relapse in patients receiving BEAM therapy (HR 4.34; 95% CI 2.45-7.70; P <0.001).

The researchers reported that in a multivariable regression analysis, patients who received TT-BCNU had a higher risk of relapse than patients who received TBC (HR 1.79; 95% CI 1.07-2.98; P = 0.03 ). These two groups showed a similar risk for all-cause mortality more than 6 months after stem cell transplantation (HR 1.54; 95% CI 0.93-2.55; P = 0.10). The TT-BCNU cohort also showed a lower risk of non-relapse mortality (HR 0.50; 95% CI 0.29-0.87; P = 0.01).

The study was limited by potential biases in patient selection and center-specific practices regarding the choice of conditioning regimen, the researchers wrote. In particular, they found that the use of thiotepa-based therapies has been more applied than BEAM in recent years. The researchers also wrote that “Important elements of data were not available, including the types of methotrexate-based induction, whether or when patients received whole-brain radiation therapy, whether pharmacokinetically targeted busulfan was used, whether additional consolidation was used after HCT, and what therapies have been used after relapse such as immunotherapies and Bruton’s tyrosine kinase inhibitors. “

“In this study, thiotepa-based conditioning regimens were associated with favorable results, suggesting that the use of carmustine / etoposide / cytarabine / melphalan should be avoided in patients with PCNSL,” wrote Scordo and colleagues.

reference

Scordo M., Wang TP, Ahn KW et al. Results related to thiotepa-based conditioning in patients with primary central nervous system lymphoma after autologous hematopoietic cell transplantation. JAMA Oncol. May 6, 2021. doi: 10.1001 / jamaoncol.2021.1074