Sobuzoxane-Containing Regimens Show Promising Response As Salvage Therapy for Relapsed or Refractory Angioimmunoblastic T-Cell Lymphoma (AITL) and Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS)
Authors: Shimizu Ikuo , Takeda Wataru , Kirihara Takehiko , Sato Keijiro , Fujikawa Yuko , Ueki Toshimitsu , Hiroshima Yuki , Sumi Masahiko , Ueno Mayumi , Ichikawa Naoaki , Kobayashi Hikaru 
Published: October 2019

Abstract
Abstract 4849

Background:
Peripheral T-cell lymphoma (PTCL) is an intractable entity with limited response to CHOP-like regimens or more intensive regimens. Although some relapsed or refractory patients may benefit from allogeneic stem cell transplantation, management of elderly patients remains problematic. Sobuzoxane (MST-16) is an oral topoisomerase II inhibitor developed and approved in Japan (Narita T et al. Cancer Chemother Pharmacol 1990). Some anecdotal reports revealed its activity against refractory or relapsed PTCLs as a single-drug regimen or in combination regimens.

Patients and Methods:
We retrospectively reviewed consecutive cases of patients with angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) who were refractory to or relapsed after CHOP-like chemotherapy during the period spanning January 1990 to March 2012 at Nagano Red Cross Hospital (Nagano, Japan). Diagnosis was performed by certified pathologists based on biopsy samples and flow cytometry. We compared efficacy, safety, and survival time between patients who underwent MST-16-containing regimens and other salvage regimens, including autologous or allogeneic stem cell transplantation.

Results:
Among 40 patients with AITL or PTCL-NOS, 27 (median age, 65 years; range, 48–86) were administered salvage chemotherapy. The MST-16 group (n=13) received MST-16 alone (9), MST-16 and etoposide (3), or MTX-HOPE (methotrexate, hydrocortisone, vincristine, MST-16, and etoposide) (1). The median number of previous regimens was 3 (range 1–4). The non-MST-16 group (n=14) consisted of multiple regimens including EPOCH (2), ESHAP (2), CEPP (cyclophosphamide, etoposide, procarbazine, and prednisolone) (1), IVAM (2), DeVIC (1), DHAP (1), ABEP (doxorubicin, bleomycin, etoposide, and prednisolone) (1), or high dose therapy with autologous or allogeneic stem cell transplantation (3). Patients in the MST-16 group were of significantly higher age (p=0.027) and had less hepatosplenomegaly (p=0.028) compared to those in the non-MST-16 group. No significant difference was observed in patient performance status, B symptoms, LDH, immunoglobulin values, International Prognostic Index (IPI) scores, and Prognostic Index for T-cell lymphoma (PIT) scores between the two groups. Among MST-16 group, overall response rate was 62.1% (CR 31.0%, PR 31.0%). Notably, additional patients (14.3%) achieved durable SD by palliative MST-16 chemotherapy. With a median observation period of 25 months, median survival time was significantly longer in the MST-16 group compared to the non-MST-16 group (23 months vs. 4 months, respectively; p=0.027). Those with a longer remission period over 6 months due to a CHOP-like regimen tended to respond better to MST-16 salvage regimens (p=0.059). With respect to adverse events, two deaths occurred (one patient with pulmonary aspergillosis following ABEP, and one patient with pneumocystis pneumonia following MST-16).

Conclusions:
Although this study was of a small scale and retrospective, it supports the notion that MST-16-containing regimens may present a promising approach for relapsed/refractory AITL or PTCL-NOS patients, particularly for those who relapse following a long remission of over 6 months due to a CHOP-like regimen, those not indicated for SCT, and those for whom steroid use is difficult. Given the pleomorphic nature of these entities, there remains the possibility that selection bias may have accounted for the difference observed between the two arms. Further prospective studies with other approaches (e.g., biological or immunohistopathological) may lead to the identification of pathologies other than hepatosplenomegaly that benefit from MST-16.

Disclosures:
No relevant conflicts of interest to declare.