Brentuximab Vedotin Improves HCT-CI, CR Status, and Peri-Transplant Toxicity In Patients With Relapsed/Refractory Hodgkin Lymphoma Heading To RIC Allo-HCT

Abstract

BackgroundThe prognosis of patients with Hodgkin lymphoma (HL) who relapse following autologous hematopoietic cell transplantation is poor. Although reduced intensity allogeneic hematopoietic cell transplantation (RIC allo-HCT) can induce durable remissions in some patients with relapsed/refractory HL, its use is limited by patient co-morbidities, lack of disease control prior to HCT, and transplant related morbidities/mortalities. Brentuximab vedotin (BV), a novel antibody-drug conjugate, has a 75% objective response rate in patients with relapsed/refractory HL (Younes 2012). We performed a retrospective analysis comparing patient characteristics prior to HCT and outcomes after HCT in relapsed/refractory HL patients who received BV and underwent RIC allo-HCT versus those who did not receive BV but underwent RIC allo-HCT. MethodsBetween Jan 2003 and July 2009 (Pre-BV era), we identified a consecutive case-series of 23 HL patients who underwent RIC allo-HCT with no prior BV exposure (no-BV group). From July 2009 to Dec 2012, we identified a consecutive case-series of 21 additional HL patients who received BV prior to RIC allo-HCT (BV group). Co-morbidities at the time of HCT were measured by the HCT-CI. The Bearman scale was used to capture toxicities associated with RIC allo-HCT. PFS and OS were calculated using Kaplan-Meier method. ResultsBaseline characteristics are listed in Table 1. All patients received fludarabine and melphalan conditioning regimens. Groups were similar in terms of age, stage, response to induction, number of prior therapies, donor type, cell source, and prior auto-HCT. Groups differed in terms of GVHD prophylaxis (institutional shift to tacro/siro from 2005), remission status, and co-morbidity index (HCT-CI) at the time of HCT. Patients in the BV group were more likely to be in complete remission (CR) at the time of transplant (p=0.04). The median HCT-CI was better in the BV group (0 vs. 2, p=0.003). Also the Bearman toxicity score during transplant showed fewer grade III-IV events in the BV patients (0 vs. 7, p=0.015).Table 1RIC allo-HCT following BV: BV group (n=21)RIC allo-HCT: no-BV group (n=23)Median age (range)31 (22, 55)37 (16, 63)Median number of prior regimens (range)4 (3, 6)4 (3, 6)Prior Auto-HCT19/21 (90.5%)19/23 (82.6%)Stages at diagnosisI-II: 9 (42.9%)III-IV: 11 (52.4%)Unknown: 1I-II: 11 (47.8%)III-IV: 11 (47.8%)Unknown: 1Median number of cycles of b-vedotin (range)7 (2, 16)Response to inductionRefractory: 5 (23.8%)Relapsed: 16 (76.2%)Refractory: 7 (30.4%)Relapsed: 16 (69.6%)ChemosensitivitySensitive: 19(90.5%)Resistant: 2 (9.5%)Sensitive: 16 (69.6%)Resistant: 7 (30.4%)Disease status at transplantationCR 6 (28.9%)PR: 9 (42.9%)SD/PD: 6 (28.6%)CR 1 (4.3%)PR: 9 (39.1%)SD/PD: 13 (56.5%)Co-morbidity score at transplant (HCT-CI)0 (0, 3)2 (1, 4)Type of transplantMUD: 11 (52.4%)MRD: 10 (47.6%)MUD: 11(47.8%)MRD: 12 (52.2%)Conditioning regimenFludarabine/melphalan 100%Fludarabine/melphalan 100%GVHD prophylaxisTacro/Siro: 16 (76.2%)Tacro/Siro/MTX: 3CsA/MTX: 2Tacro/Siro: 12 (52.2%)Tacro/Siro/MTX: 4Tacro/MTX: 1CsA/Cellcept: 3CsA/Cellcept/ATG: 1CsA/Cellcept/MTX: 2WBC engraftment (range)14 (11, 21)15 (10, 20)Plt engraftment (range)13 (11, 26)13 (8, 35)Chimerism100%100%aGVHD I-IV, III-IV28.6% , 4.8%47.8%, 8.7%cGVHD76.2%78.3%Bearman ToxicityGrade III-IV07The median follow-up for living patients in the no-BV group was 70.2 month and 23.3 months for the BV group (5 year lag for BV group). The 2-yr PFS for the no-BV group was 26.1% (95% CI: 21.5, 30.9) compared to 51.8% (95% CI: 38.5, 63.6) for the BV group, p=0.099. The 2-yr cumulative incidence of relapse/progression for no-BV was 56.5% (95% CI: 33.2, 74.4) compared to 28.9% (95% CI: 9.9, 51.4) for BV, p= 0.066. The 2-yr OS was 56.5% (95% CI: 44.3, 67) for no-BV compared to 66.6% (95% CI: 47.8, 80.0) for BV. Non-relapse mortality (NRM) at day 100 was 4.3% and 17.4% at 1 yr for the no-BV group. For the BV group NRM at day 100 was 0% and 11.8% at 1 yr. The rate of aGVHD and cGVHD were 56.5% and 78.3% for no-BV, and 33.3% and 76.2% for BV groups, respectively. ConclusionBV prior to RIC allo-HCT in relapsed HL leads to improvements in 1) HCT-CI 2) CR status at time of transplant, and 3) reduced peri-transplant toxicity. Disclosures:Chen:Seattle Genetics, Inc.: Consultancy, Research Funding, Speakers Bureau, Trave expenses Other. Siddiqi:Seattle Genetics: Speakers Bureau.