Study Examines High-Dose Therapy, ASCT for Rare Type of Non-Hodgkin Lymphoma

A recently published retrospective study assessed the real-world response to either conventional therapy or to high-dose therapy (HDT) followed by autologous blood stem cell transplantation (ASCT) as a first-line therapy for primary central nervous system non-Hodgkin lymphomas (PCNS-NHLs).

PCNS-NHLs are rare extranodal B-cell lymphomas with poor prognoses and no standard treatments. In an ongoing phase 3 study, methotrexate (MTX), rituximab, thiotepa, and cytarabine were associated with a significantly longer overall survival (OS) and progression-free survival (PFS), although another study did not reach the same conclusion.

The current German study, looking at PFS and OS by comparing 2 treatment groups, was conducted at the University Hospital Duesseldorf.

Researchers retrospectively collected long-term follow-up data of 61 consecutive patients with PCNS-NHL from January 2004 to December 2016. The median age was 64 years; most were male. Patients in the high-dose therapy (HDT) group were younger compared with patients in the conventional therapy (CT) group (54.6 years vs. 66.5 years, P < .001). Median follow-up of all surviving patients was 85.5 months (range 57–196) in February 2021.

Results were analyzed with a Cox regression model to determine the clinical predictors for OS and PFS.

Conventional Chemoimmunotherapy Group

Thirty-six patients received conventional chemoimmunotherapy (cCIT) only (CT-group), and regimens varied. Twenty-eight patients (78%) received single-agent MTX with or without rituximab; a median of 3 cycles (range 2–8) of high-dose MTX was given. Eight patients (22%) received various other regimens, and 2 patients received consolidating radiotherapy.

In the CT-group, the overall response rate (ORR) was 61% (Complete Remission [CR] 47%, Partial Resmission [PR] 14%), and there were 8% treatment-related deaths (TRD).

PFS was 31.8 months, and OS was 57.3 months.

High-dose Chemotherapy Group

Seventeen patients received an induction cCIT followed by HDT and ASCT. The induction therapy before HDT consisted mainly of rituximab and high-dose MTX (median 3 cycles; range 2–6 cycles), high-dose cytarabine and thiotepa (median 2 cycles; range 1–4 cycles). All patients achieved an objective response after induction therapy, with 5 (29%) reaching CR and 12 (71%) reaching PR.

The conditioning regimen consisted of carmustine and thiotepa, with or without rituximab, in 14 patients (82%). Three patients (18%) received carmustine, etoposide, cytarabine and melphalan, with or without rituximab as a conditioning regimen.

In the HDT-group, the ORR was 88% (59% CR, 29% PR), and there were 6% TRD. Median PFS and OS were not reached at 5 years. The 5-year PFS and OS were 64.7%.

Outcomes

Eight patients (22%) were alive in CR/PR in the CT-group after a median follow-up of 100 months, and 28 patients died (78%, 24 Progressive Disease [PD], 2 TRD, 2 deaths in remission).

After HDT and ASCT, 10 patients (59%) were still alive in CR/PR after a median follow up of 71 months; 1 patient was treated for PD, and 7 had died (41%, 6 PD, 1 TRD).

All patients achieving CR prior to HDT achieved durable CR.

In the univariate analysis, patients in the HDT group had significantly better PFS (not reached vs 31.8 months, P  =  .004) and OS (not reached vs 57.3 months, P  =  .021). But the multivariate analysis did not show a statistically significant difference that HDT was better for survival.

cCIT led to CR in 29% and an ORR of 100% among patients in the HDT group, and HDT further improved the CR rate to 59%. The authors pointed out that “all patients that achieved CR prior to HDT had a better outcome than those achieving CR after the HDT,” which highlights that an effective induction therapy before starting a consolidation therapy is vital.

Most patients received a carmustine and thiotepa-based HDT as a conditioning regimen, which proved to be more effective than other regimens commonly used in peripheral lymphomas, the authors said.

The induction and consolidation therapy used in this study lacked standardization, the authors said, and randomized comparative studies are needed to understand the role of HDT and ASCT for PCNS-NHL.

Reference

Brezina T, von Dewitz H, Schroeder T, et al. First-line high-dose therapy and autologous blood stem cell transplantation in patients with primary central nervous system non-Hodgkin lymphomas—a single-centre experience in 61 patients. Ann Hematol. Published online January 4, 2022. doi:10.1007/s00277-021-04745-z