Combining BeEAM with Brentuximab Vedotin for High-Dose Therapy in CD30 Positive Lymphomas before Autologous Transplantation-A Phase I Study.

The prognosis for patients with CD30+ lymphomas (Hodgkin lymphoma and various T-cell lymphomas) relapsing after autologous stem cell transplantation (ASCT) is critical. Brentuximab vedotin (BV), an ADC targeting CD30, is an obvious candidate for inclusion into high-dose chemotherapy (HDCT) regimens to improve outcomes. This single center phase I trial investigated 12 patients with CD30+ lymphoma (AITL: n = 5; relapsed HL: n = 7; median of two previous treatment lines) undergoing ASCT. In a 3 + 3 dose escalation design, 12 patients received a single BV dose at three dose levels (DL) (0.9/1.2/1.8 mg/kg b.w.) prior to standard BeEAM. All patients were treated as planned; no dose limiting toxicities (DLTs) occurred at DL 1 and 2. At DL 3, one DLT (paralytic ileus, fully recovering) occurred. Grade III febrile neutropenia occurred in one patient, and two others had septic complications, all fully recovering. Median hospitalization was 23 days. Hematologic recovery was normal. Six of twelve (50%) patients achieved CR. PFS and OS at 1 year were 67% (n = 8/12) and 83% (n = 10/12), respectively. The addition of brentuximab to standard BeEAM HDCT seems to be safe. We observed a CR rate of 75% post-ASCT in a highly pretreated population. The efficacy of this novel HDCT combination with BV at a 1.8 mg/kg dose level needs to be explored in larger studies.