The role of auto-HSCT in PET-positive, chemosensitive DLBCL

Autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard consolidation option for transplant-eligible patients with relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL). The addition of anti-CD19 chimeric antigen receptor (CAR) T-cell therapies to the management of patients with relapsed and/or refractory DLBCL has led to a reduction in the number of auto-HSCT procedures in the US, according to data from the Center for International Blood and Marrow Transplant Research (CIBMTR). The data suggest that CAR T-cell therapy is increasingly taking the place of auto-HSCT in patients with PET-positive, relapsed DLBCL who achieve only a partial remission (PR) to salvage therapy. To determine whether auto-HSCT should still be considered an option for such patients, Nirav Shah et al. investigated the outcomes of patients with chemosensitive, PET-positive DLBCL who achieved a PR before undergoing auto-HSCT, using the CIBMTR database.¹ Their results were recently published in Blood, and here we summarize their findings.

Study design

Regularly collected, long-term data on patients who underwent auto-HSCT between 2003 and2018 were evaluated. The primary endpoint was overall survival (OS), and secondary endpoints were non-relapse mortality (NRM), relapse/progression, and progression-free survival (PFS).

The study population included adult patients (≥ 18 years of age) with DLBCL who had a PR to chemotherapy, a positive PET scan, and subsequently underwent auto-HSCT. Only patients receiving first-line chemoimmunotherapy with a rituximab (R) and anthracycline combination (either R-CHOP or R plus dose-adjusted EPOCH) were included. The conditioning regimens were restricted to carmustine, etoposide, cytarabine, and melphalan (BEAM); cyclophosphamide, carmustine and etoposide (CBV); and busulfan and cyclophosphamide (Bu/Cy).

Results

Patient characteristics

The number of patients included in the analysis was 249. Patients were divided into two groups based on the presence or absence of early chemoimmunotherapy failure (ECF), defined as not achieving a complete remission following the first line of chemoimmunotherapy, or relapse/progression within 1 year after initial diagnosis.

Selected characteristics of the patients in a PET-positive PR before undergoing auto-HSCT are presented in Table 1. Most characteristics were comparable, however the median age, stage III–IV disease at the time of diagnosis, and primary refractory status after the first line of therapy differed significantly.

Table 1. Selected baseline characteristics¹

Outcomes

The comparisons of key outcomes among the two patient groups are provided in Table 2.

Table 2. Adjusted auto-HSCT outcomes according to patient group¹

In a multivariate analysis, NRM, relapse/progression, and PFS were not found to be significantly different between the two groups, while mortality risk was significantly higher in the ECF group (p = 0.03).

Subgroup analyses

In a subgroup analysis of patients who received ≥ 2 lines of therapy prior to auto-HSCT, there were no significant differences in NRM or relapse/progression among the no ECF (n = 64) and ECF (n = 150) groups.

The absence of ECF was associated with a significantly higher 1-year PFS compared with the ECF group (50% vs 67%; p = 0.01), however there was no significant difference in the 5-year PFS.

The 1- and 3-year OS rates were also significantly higher in patients with no ECF compared with patients with ECF (1-year OS, 84.6% vs 63.2%, p < 0.001; 3-year OS, 69.1% vs 51.9%, p = 0.01). However, the 5-year OS rates were not significantly different between the groups.

Another subgroup analysis of patients who received a platinum-based regimen at a second-line setting did not yield any significant differences among the groups in terms of the 5-year PFS and OS.

Conclusion

The results of this study demonstrate that auto-HSCT can provide durable disease management in patients with relapsed DLBCL achieving PET-positive PR after salvage therapy. Subset analyses showed similar outcomes in patients with and without ECF.

To date, no studies have demonstrated that CAR T-cell therapy is superior to auto-HSCT in chemosensitive disease. Studies comparing the standard approach that consists of salvage therapy followed by auto-HSCT in patients responding to CAR T-cell therapy without salvage attempt are ongoing (NCT03391466 [ZUMA-7] and NCT03570892 [BELINDA]); read more here. While the outcomes of these trials will be key to inform clinical practice, the authors believe it remains important to consider auto-HSCT consolidation in patients achieving only a PR after salvage therapy for the following reasons: favorable results observed with auto-HSCT, the lack of data favoring CAR T-cell therapy over auto-HSCT, the higher cost associated with CAR T-cell therapy, the potential of CAR T-cell therapy as a salvage option in relapse after auto-HSCT, and the poor prognosis for patients relapsing after CAR T-cell therapy.

The study limitations included retrospective study design and the lack of central evaluation of PET results.