Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation

Abstract

Hodgkin lymphoma (HL) relapsing after allogeneic stem cell transplantation (alloSCT) presents a major clinical challenge. In the present investigation, we evaluated brentuximab vedotin, a CD30-directed Ab-drug conjugate, in 25 HL patients (median age, 32 years; range, 20-56) with recurrent disease after alloSCT (11 unrelated donors). Patients were > 100 days after alloSCT, had no active GVHD, and received a median of 9 (range, 5-19) prior regimens. Nineteen (76%) had refractory disease immediately before enrollment. Patients received 1.2 or 1.8 mg/kg of brentuximab vedotin IV every 3 weeks (median, 8 cycles; range, 1-16). Overall and complete response rates were 50% and 38%, respectively, among 24 evaluable patients. Median time to response was 8.1 weeks, median progression-free survival was 7.8 months, and the median overall survival was not reached. Cough, fatigue, and pyrexia (52% each), nausea and peripheral sensory neuropathy (48% each), and dyspnea (40%) were the most frequent adverse events. The most common adverse events ≥ grade 3 were neutropenia (24%), anemia (20%), thrombocytopenia (16%), and hyperglycemia (12%). Cytomegalovirus was detected in 5 patients (potentially clinically significant in 1). These results support the potential utility of brentuximab vedotin for selected patients with HL relapsing after alloSCT.

Trial registration: ClinicalTrials.gov NCT00947856 NCT01026233 NCT01026415.

Figure 1

OS and PFS after brentuximab vedotin therapy.

Figure 2

PFS by response to brentuximab vedotin. Twenty-four patients were evaluable; 1 patient died before the first response assessment. Nine patients had CR, 3 had PR, and 12 had no objective response.

Figure 3

Case study before and after brentuximab vedotin therapy. Positron emission tomography scans before (A) and after (B) 9 cycles of brentuximab vedotin for a 20-year-old patient who had been diagnosed with HL 3 years earlier. The patient had received 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide followed by external beam radiation that yielded a CR lasting 2 months. She was next treated with 2 cycles of ICE, achieving a PR lasting 1 month. Subsequently, gemcitabine, vinorelbine, and doxorubicin (GND), followed by BEAM autoSCT yielded a PR lasting 3 months. She underwent alloSCT for relapsed disease, conditioned with busulfan, fludarabine, and total body irradiation (200 cGy) and had a matched, unrelated donor, but experienced disease progression 4 months after alloSCT. She received her first dose of brentuximab vedotin in December 2009, achieved a PR before the third dose, and a CR was reported after the ninth dose. She completed 16 treatment cycles and remained in CR at the last contact, 6 months after the last dose of brentuximab vedotin.

Figure 4

CMV history and CMV viremia after brentuximab vedotin therapy. *No evidence of CMV viremia or clinical infection was reported. CMV viremia is defined as evidence that CMV is active and replicating but has not caused an invasive infection. †Potentially clinically significant.