Abstract
Background: PTCL is a heterogeneous group of hematologic malignancies associated with a poor prognosis for most subtypes. In the relapsed setting, hematopoietic stem cell transplantation (HSCT) is the only potentially curative option for patients with PTCL. However, many patients are not able to achieve an adequate response to allow for HSCT.
Belinostat (Beleodaq) is a potent pan-histone deacetylase inhibitor that was recently approved in the US for the treatment of patients with R/R PTCL. Approval was based on data from the pivotal Phase 2 BELIEF study that enrolled 129 patients with R/R PTCL (N = 120 evaluable), and demonstrated durable clinical benefit and tolerability. This analysis presents data for 12 of the enrolled patients (9 evaluable) who proceeded to HSCT following belinostat treatment.
Methods: Patients with R/R PTCL received belinostat as a 1000 mg/m2IV infusion on Days 1-5 of a 21-day cycle. The primary endpoint of the study was Objective Response Rate (ORR; Complete Response [CR] + Partial Response [PR]) determined by an Independent Review Committee (IRC). We present efficacy and safety data for the subset of 12 patients who subsequently went on to HSCT.
Results: Among 12 patients who subsequently proceeded to HSCT, 4 went on to receive an autologous HSCT and 8 received an allogeneic HSCT; 8 patients (67%) were female and 4 (33%) were male, and the median age was 54.5 (range 31-71) years. The median number of prior anticancer therapies was 2 (range 1-8), including 3 patients with prior autologous HSCT. The median number of belinostat treatment cycles was 2.5 (range 1-14) compared to the median of 2.0 (range 1-8) in the overall study population. Most patients in this subgroup had PTCL-Not Otherwise Specified (58.3%), angioimmunoblastic T-cell lymphoma (16.7%), or anaplastic large cell lymphoma (16.7%); 41.7% of patients had Stage IV disease.
Three of the 12 patients were not evaluable for response due to insufficient histological material for confirmation by central pathologic analysis. The IRC-confirmed ORR for the 9 evaluable patients was 33.3% vs 25.8% in the study overall, and included 2 CRs, 1 PR, 2 patients with stable disease (SD) and 3 patients with progressive disease (PD). Duration of Response after transplant ranged from 41-261 days for the 3 belinostat responders. At last study contact, 2 patients had died from cardiac events (unrelated to belinostat) and 10 remained alive, with Overall Survival (OS) ranging from 8-23+ months. Most adverse events (AEs) were Grade 1-2, with two treatment-related Grade ≥3 AEs (neutropenia and prolonged QT interval); 3 serious AEs (arthralgia, lower limb fracture, and pyrexia) were reported in this subgroup.
Conclusions: Belinostat was well tolerated in previously treated patients with R/R PTCL and enabled some patients to proceed to HSCT. Three patients responded and went on to HSCT following belinostat; the remaining patients had HSCT following SD (2), PD (4) or were not evaluable (3). OS was prolonged when compared to historical controls.
Summary of Patients Treated with Belinostat Who Subsequently Went on to Hematopoietic Stem Cell Transplantation Sorted by Subtype and Response Table 1PatientSubtype(Stage)Prior RegimensECOGPSBelinostat CyclesIRC ResponseOS(months)DoR(days) Evaluable Patients931-003^PTCL-NOS (IIIB)3114CR11.56261907-006PTCL-NOS (IIA)5 + auto SCT02SD13.93-907-007^PTCL-NOS (IVA)402SD12.09-907-005^PTCL-NOS (IIIA)202PD13.63-140-002PTCL-NOS (IVA)817PD17.64-914-006PTCL-NOS (IIIA)4 + auto SCT02NE13.73-245-001AITL (UNK)106PR19.9141221-003ALCL ALK– (IA)2 + auto SCT011CR20.4173907-001ALCL ALK– (IVA)204PD22.87- Non-Evaluable Patients*914-002PTCL-NOS (IVB)102PD7.75-147-002^AITL (IIIB)221NE9.43-147-001Hepatosplenic TCL (IVA)103NE10.22-
AITL = angioimmunoblastic T-cell lymphoma; ALCL = anaplastic large cell lymphoma; ALK = alkaline phosphatase; auto = autologous; CR = complete response; DoR = duration of response; ECOG = Eastern Cooperative Oncology Group; IRC = independent review committee; NE = not evaluable; NOS = not otherwise specified; OS = overall survival; PD = progressive disease; PR = partial response; PS = performance status; PTCL = peripheral T-cell lymphoma; SCT = stem cell transplantation; SD = stable disease; TCL = T-cell lymphoma
*Lack of central pathologic confirmation resulted in exclusion from the evaluable population
^Autologous hematopoietic SCT
Disclosures
Al-Ali: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Hsu:Spectrum Pharmaceuticals: Employment. Choi:Spectrum Pharmaceuticals: Employment. Allen:Spectrum Pharmaceuticals: Employment. Visser:Sanofi: Membership on an entity's Board of Directors or advisory committees. Horwitz:Celgene: Consultancy, Research Funding; Millenium: Consultancy, Research Funding; Infinity: Research Funding; Kiowa-Kirin: Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy; Jannsen: Consultancy.
Long-term Remission After Allogeneic Hematopoietic Stem Cell Transplantation for Refractory Cutaneous T-Cell Lymphoma
