Brentuximab Vedotin (BV) Does Not Impair Autologous Peripheral Blood Stem Cell Mobilization and Collection in Refractory/Relapsed CD30+ Lymphoma Patients Undergoing High-Dose Chemotherapy and Autologous Stem Cell Transplant (HDC-ASCT)

Introduction. Salvage chemotherapy followed by HDC-ASCT is considered standard of care for chemosensitive patients who have relapsed after initial therapy. CD30 is commonly expressed in Hodgkin Lymphoma (HL) and in some cases of non-Hodgkin lymphoma (NHL). Brentuximab vedotin (BV), an antibody-drug conjugate that targets CD30, induces high response rates and is now used in the salvage setting prior to HDC-ASCT. It is not clear if BV use peri-mobilization would influence mobilization and collection of autologous CD34+ stem cells. We therefore examined 42 patients who were treated with BV prior to HDC-ASCT.

Methods. We retrospectively reviewed the HDC-ASCT databases of University Hospitals Case Medical Center (UHCMC) and MD Anderson Cancer Center (MDACC) and identified 42 patients who were treated with BV prior to HDC-ASCT between February 2009 and April 2014. The median age was 37 years (range, 18-67) and 52% (n=22) were male. Diagnoses were HL (n=30; 71%;), and NHL (n=12; 29%; anaplastic large cell, n=6; diffuse large B-cell, n=3; unknown subtype, n=3). Median times from diagnosis to transplant, from initial BV treatment to transplant and from last BV treatment to stem cell collection were: 21 months (range, 10-210), 5 months (range, 1.5-16.8), and 30 days (range, 2-280), respectively. Our subjects had failed multiple conventional treatments with a median of 3 (range, 2–8) lines of treatment before HDC-ASCT; 38% (n=16) received involved field radiation therapy. BV was given at 1.8 mg/kg IV every 21 days. Median number of BV cycles was 4 (range, 1-16) and the overall response rate to treatment was 71% (CR 55% + PR 16%). Thirty patients (71%) were in complete remission (CR) at the time of transplant (CR2 = 6; CR≥3 = 24), 4 (10%) were in partial remission (PR) (PR2 = 1; PR≥3 = 3), 6 patients (14%) had stable disease and 2 patients (5%) were transplanted with progressive disease. Stem cell collection target was 5 x 10⁶ CD34+ cells/Kg. Mobilization regimens used were chemotherapy/G-CSF-based in 32 patients (76%) and Plerixafor/G-CSF-based in 10 patients (24%). Use of chemotherapy/G-CSF in first mobilization was standard at MDACC, whereas plerixafor/G-CSF was used as first mobilization at UHCMC.

Results. Thirty-nine (92.8%) of 42 patients were successfully mobilized on the first attempt. Second mobilization was required in 3 cases (7.1%). Second mobilization regimens included Cyclophosphamide/G-CSF (n=2) and Plerixafor/G-CSF (n=1). The median number of infused CD34+ cells was 5.46 x10⁶/kg (range, 1.65-54.78 x10⁶/kg). All patients engrafted neutrophils and platelets at a median time of 10 days (range, 9-13), and 10.5 days (range, 7-35), respectively. The median time to RBC transfusion independence was 8 days (0-34). With a median follow-up of 12 months (range, 0–63), day 100 treatment-related mortality was 0%. The one-year actuarial event-free and overall survival is 50.5% and 84.1%, respectively.

Conclusion. Within the limitations of this retrospective study, BV before HDC-ASCT did not adversely affect peripheral blood stem cell mobilization, collection and engraftment in a cohort of heavily pre-treated, relapsed/refractory patients with CD30+ lymphomas.