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Two commonly used thiotepa-based conditioning regimens were associated with favorable outcomes among patients with primary central nervous system lymphoma (PCNSL) undergoing autologous hematopoietic cell transplant (AHCT), according to a retrospective observational study.

Patients in the thiotepa/busulfan/cyclophosphamide (TBC) cohort and those in the thiotepa/carmustine (TT-BCNU) cohort had 3-year adjusted progression-free survival (PFS) rates of 75% and 76%, respectively, which were substantially higher than the PFS rate of 58% in a cohort that received carmustine/etoposide/cytarabine/melphalan (BEAM).

"Our findings suggest that thiotepa-containing regimens should be considered the standard in patients with PCNSL wherein AHCT is determined to be the consolidation of choice," wrote Michael Scordo, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues in .

PCNSL is a rare extranodal subtype of non-Hodgkin's lymphoma that is diagnosed in approximately 1,500 patients in the U.S. each year. High-dose therapy and AHCT are commonly used consolidation strategies, but according to Scordo's group, there is no consensus on the best conditioning regimen.

The authors used data from the Center for International Blood and Marrow Transplant Research registry. The study cohort included 603 adults with PCNSL who underwent AHCT from January 2010 to December 2018. Of these patients, 263 received TBC, 275 received TT-BCNU, and 65 received BEAM.

The primary outcome was PFS, while secondary outcomes included relapse incidence, nonrelapse mortality, and overall survival (OS).

The adjusted PFS rates at 1 year for the TBC, TT-BCNU, and BEAM cohorts were 83%, 86%, and 72%, respectively. After adjusting for age, Karnofsky performance status, and disease status/time from diagnosis to transplant, TT-BCNU was associated with a similar PFS (HR 1.04, 95% CI 0.72-1.50) compared with TBC, while BEAM was associated with an inferior PFS (HR 1.74, 95% CI 1.10-2.75).

For the TBC, TT-BCNU, and BEAM cohorts, adjusted OS rates at 1 year were 87%, 92%, and 90%, respectively. At 3 years, these rates were 81%, 78%, and 69%, respectively.

In multivariable regression analyses, the use of TT-BCNU was associated with a reduced risk of nonrelapse mortality (HR 0.50, 95% CI 0.29-0.87, P=0.01) compared with the use of TBC, though no significant association was observed in the BEAM cohort (HR 0.50, 95% CI 0.20-1.28, P=0.15).

However, patients who received TT-BCNU had an increased risk of relapse or progression (HR 1.79, 95% CI 1.07-2.98, P=0.03) compared with those who received TBC, as did those who received BEAM (HR 4.34, 95% CI 2.45- 7.70, P<0.001), though use of TT-BCNU was associated with a lower risk versus BEAM (HR 0.41, 95% CI 0.25-0.69, P<0.001).

In subgroup analyses, patients age 59 and younger who received TBC had a lower risk of relapse, better PFS and OS, and comparable nonrelapse mortality at 3 years compared with those who received TT-BCNU. On the other hand, patients age 60 and older who received TBC compared with TT-BCNU -- despite similar incidences of relapse (14% vs 15%) -- had worse 3-year PFS and OS rates, likely reflecting higher nonrelapse mortality (21% vs 13%).

"This finding suggests that TBC may be more suited to patients who are younger and fitter, particularly those with more advanced disease beyond complete remission given the better protection from relapse, and that TT-BCNU may be more suited to patients who are older with more comorbid conditions," Scordo and colleagues wrote.

While the study provided evidence supporting the efficacy of thiotepa-based conditioning regimens, there is a need to better define the safest and most effective thiotepa regimens for all patient populations, particularly those 60 and older, noted John M. Hill Jr., MD, and Kenneth R. Meehan, MD, both of the Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center in Lebanon, New Hampshire, in an accompanying .

"We agree with the authors' suggestion to consider the TBC regimen for younger fit patients while reserving TT-BCNU for older patients with comorbidities and compromised performance status," they wrote. "Accordingly, age- and risk-stratified prospective randomized trials are warranted to better define the role of TBC, TT-BCNU and TT-busulfan regimens in minimizing consolidative transplant toxic effects and optimizing long-term posttransplant outcomes for all patients with this challenging malignant neoplasm."

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