A Randomized Study of Interferon α-2b Versus No Treatment as Consolidation After High Dose Therapy and Autologous Stem Cell Transplantation for Patients With Relapsed Lymphoma

Abstract

Background. Patients with lymphoma who have experienced a first relapse or progression and have disease deemed sensitive to salvage chemotherapy nevertheless have a high likelihood of having a second relapse. To decrease the likelihood of a second relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT), interferon (IFN) ␣-2b was given in a prospective randomized international trial. Methods. In this trial, 221 patients with varying histologic diagnoses (8 small lymphocytic, 37 follicular, 9 mantle, 90 diffuse large B-cell, 20 peripheral T-cell, 3 high-grade B-cell non-Hodgkin lymphoma, and 54 Hodgkin lymphoma) were randomly assigned to receive no further treatment (arm A: 117 patients) or IFN␣-2b, 3 MU three times weekly, for 18 months (arm B: 104 patients). Results. In arm B, 21 patients (20%) did not receive IFN␣-2b because of early progression or absence of hematologic recovery, 29 patients (28%) completed the 18 months of treatment, and 54 patients (52%) interrupted treatment because of progression (23%) or toxicity (29%). Event-free survival and overall survival were not different between the two arms on an intent-to-treat analysis and also if analysis was restricted to patients who were alive and had not experienced disease progression three months after transplantation. The study was not sufficiently powered to evaluate effects in histologic subtypes. Conclusion. In this trial, post-autograft IFN␣-2b did not improve outcomes in a heterogeneous group of patients with lymphoma.

Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review

“…IL-2 and IFN-a combination after ASCT showed no significant differences in the OS [47,77]. Also, IFN-a-2b maintenance therapy did not improve OS [45].…”

“…EFS and OS rates were statistically not different between the 2 arms in an intent-to-treat analysis and the study was insufficiently powered to evaluate treatment effects in histologic subtypes. Interestingly, 50% of patients did not complete IFN-a-2b maintenance therapy because of disease progression or toxicity, which may have affected treatment outcomes [45]. In the second study, no significant differences in PFS (P ¼ .56) or OS rates (P ¼ .88) were observed in 194 NHL patients who were randomized to receive post-ASCT rIL-2 versus observation [46].…”

“…Bosly et al enrolled 54 patients with HL treated with HDC/ASCT. Patients were randomized to IFNa-2b maintenance versus observation [45]. The EFS and OS rates were not different between the 2 arms in an intent-totreat analysis (Table 1).…”

Post-autologous transplant maintenance therapies in lymphoma: current state and future directions

“…This approach yielded similar OS (89% vs 86%; P = 0.9) in the two arms and no significant difference in DFS or relapse rate was found. 41 Similarly, Bosly et al 42 evaluated interferon-2b maintenance therapy versus observation in 54 patients with relapsed HL following treatment with high-dose chemotherapy and ASCT. In this analysis, no EFS or OS differences were noted between the maintenance and observation arms.…”

“…In this analysis, no EFS or OS differences were noted between the maintenance and observation arms. 42 Histone deacetylases are important in a number of subtypes of lymphoma through their interaction with cell cycle progression, along with cytokine and chemokine signaling. 43,44 Panobinostat is a pan-histone deacetylase inhibitor and was found to have activity in HL, including an ORR of 27% (23% PR and 4% CR) in a phase II study.…”