Phase 2 study of suberoylanilide hydroxamic acid (SAHA) in relapsed or refractory indolent non-Hodgkin lymphoma: A California Cancer Consortium study

Abstract

18515 Background: The indolent (follicular, marginal zone and mantle cell) lymphomas tend to recur with decreasing intervals of remission post standard chemotherapy. Vorinostat (SAHA, Zolinza), an orally administered hydroxamic acid histone deacetylase inhibitor with activity against class I and II deactylases, with preclinical and clinical activity against various forms of lymphoma, is being studied in patients with relapsed or refractory indolent lymphoma. Methods: Patients with relapsed or refractory follicular, marginal zone, or mantle cell lymphoma are eligible. Vorinostat is dosed at 200 mg po twice daily for 14 consecutive days on a 21 day cycle. CT scanning and marrow biopsy is performed after every three cycles. Patients may have received up to four prior chemotherapy regimens including Zevalin or Bexxar; previous transplant is allowed. Results: 15 patients (9 female, 6 male) have been enrolled thus far. Median age is 64 (40- 78) years One patient was found to have coexisting DLBCL and was removed from study. Four patients were taken off study due to progression, three stopped due to toxicity (fatigue in a 73 yo woman who had stable to improved marginal zone lymphoma after 10 cycles, fatigue and atrial fibrillation in a 65 yo man after 7 cycles, diarrhea in a 78 year old woman after 2 cycles). Complete Response (CR) in a patient with follicular lymphoma was attained after 9 cycles, this CR persists now for eight months at the time of abstract submission off therapy. A partial response (PR) was seen in a 40 yo man with lymphoma progression despite multiple rounds of therapy, with rapidly expanding masses just prior to starting vorinostat, the largest of which was 16x12.3 cm. This lesion currently measures 7.2x4.6 cm, with disappearance of many other sites; patient continues on vorinostat. Three of the patients with continued stable disease beyond 9 cycles have marginal zone lymphoma, while the two responders (CR or PR) have follicular lymphoma. A patient with PET resolution and decreases in two of the involved sites stopping after 10 cycles due to fatigue, developed rapid progression three months after stopping vorinostat. Conclusions: Vorinostat demonstrates preliminary activity against follicular and marginal zone lymphoma. No significant financial relationships to disclose.