Histone deacetylase inhibitor abexinostat (S78454/PCI-24781) as a successful approach in a case of refractory peripheral angio-immunoblastic T-cell lymphoma, as a bridge to reduced intensity conditioning haplo-identical allogenic stem cell transplant

A 66-year-old woman presented in 2012 with an unintentional 10 kg weight loss, intermittent fevers, skin rash, generalized lymphadenopathy and hyper. Evaluation revealed histologically proven peripheral angio-immunoblastic T-cell lymphoma (AITL), (stage IV), with cutaneous and osteomedullary involvement, with two international prognostic index (IPI) risk factors and two risk factors for the prognostic index for peripheral Tcell lymphoma. The patient was treated in a clinical trial up-front and received 2-weekly CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). Evaluation after two cycles showed progressive disease. Salvage chemotherapy consisting of CarboDHAP (carboplatin, cytarabine, and dexamethasone) was started. Clinical progression with lymphadenopathy reappearance and night sweats was observed after one cycle. Treatment was switched to an ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) regimen. After six cycles, the patient achieved a complete response (CR), confirmed by chest tomography. Relapse was observed 1 year after the last ABVD cycle, with recurrence of lymph nodes by fluorodeoxyglucosepositron emission tomography/computed tomography (FDG-PET/CT), confirmed by histology (Fig. 1). The patient was included in an international, multicenter, open-label, phase II dose-escalation study of oral administration of the pan-histone deacetylase (panHDAC) inhibitor abexinostat (S78454/PCI-24781, CL178454-001). She received a dose of 80 mg orally twice daily for 14 days of every 21-day cycle. Treatment was well tolerated, with grade I diarrhea and asthenia. Restaging CT scan after four cycles revealed CR. Ten total cycles were administered. FDG-PET/CT confirmed the persistence of CR after cycle 9. The patient was subsequently evaluated for allogenic hematopoietic stem cell transplant (SCT). We performed reduced-intensity conditioning haplo-identical allogenic SCT with her daughter, using cyclophosphamide (14.5 mg/kg/d 2 days), fludarabine (30 mg/m/d 5 days), total body irradiation (2 Grays) and infusion of 4,9.10 CD34+/kg peripheral blood stem cells. Graftversus-host disease (GVHD) prophylaxis consisted of cyclophosphamide 50 mg/kg/d (day 3 and 4), cyclosporine A and mycophenolate mofetil. No acute or chronic GVHD were observed. Chimerism was total donor at day 60. The only complications were cytomegalovirus reactivation, successfully treated with ganciclovir, and an Aspergillus fumigatus documented sinusitis successfully treated with voriconazole. The patient has now reached a follow-up of 10 months post-transplant, she is in excellent general health, and without evidence of recurrent disease. The peripheral T-cell lymphomas (PTCLs), including AITL, represent 20% of mature T-cell and NK-cell neoplasms, and encompass a heterogeneous group of diseases associated with a poor prognosis. The International T-Cell Project (ITCP) and the British Columbia Cancer Agency (BCCA) series are the largest retrospective studies of PTCLs and include outcomes on 1314 and 199 cases, including 213 and 10 AITL patients