Prospective Phase 2 Trial of High-Dose Gemcitabine/Busulfan/Melphalan (Gem/Bu/Mel) with Autologous Stem-Cell Transplant (ASCT) without Post-ASCT Maintenance, in Hodgkins Lymphoma Patients at High Risk of Post-Transplant Recurrence Comparison with a Concurrent Matched Cohort Treated with BEAM

INTRODUCTION : More active high-dose regimens are needed for refractory or poor-risk relapsed Hodgkin9s lymphomas (HL), where BEAM offers poor results. Post-BEAM maintenance treatment with brentuximab vedotin (BV) x 48 weeks has recently been shown in the AETHERA trial to prolong progression-free survival (PFS) compared to placebo (2-year PFS 63% vs. 51%). We previously developed a regimen of infusional gemcitabine combined with busulfan and melphalan (Gem/Bu/Mel) pursuing inhibition by Gem of DNA damage repair. The encouraging results we saw in HL patients led us to conduct a phase 2 trial of Gem/Bu/Mel in HL patients at high risk of post-ASCT relapse. METHODS : HL patients ages 12-65 with ≥1 of the following criteria were eligible: Persistent active disease after 1 st -line chemotherapy, CR1 2 followed by infusion at a fixed dose rate of 10 mg/m 2 /min over 4.5 hours on days -8 and -3 (total daily dose of 2,775 mg/m 2 ). Each Gem infusion was immediately followed by the corresponding dose of Bu or Mel. Bu was administered intravenously from days-8 to -5 targeting a daily AUC of 4,000. Mel was infused at 60 mg/m 2 /day on days -3 and -2. ASCT was on day 0. Post-HDC involved field radiotherapy (IFRT) was considered to lesions >5 cm at the time of HDC or persistently PET+ at the 1-month post-HDC evaluation. The trial had 80% power to detect a 2-year PFS increase from 50% to 65%.The concurrent BEAM cohort included all patients eligible for this trial who received BEAM off study due to no financial coverage for ASCT in a trial or patient/physician preference. RESULTS : Eighty patients were enrolled on study between 6/11-04/15 (Table 1). There was no transplant-related mortality (TRM). The toxicity profile was manageable, including mucositis (49% G2, 40% G3), skin (22% G2, 11% G3), self-limited transaminase elevation (30% G2, 19% G3), and hyperbilirubinemia (24% G2, 19% G3) with no cases of VOD. There was 1 case of G2 pneumonitis and none of cardiac, renal or CNS toxicity. Neutrophils and platelets engrafted at median days +10 (8-12) and +12 (9-21), respectively. Eight patients received post-HDC IFRT to mediastinum ± neck ± sternum at 30.6-39.6 Gy, starting on median day +42 (41-53) post-HDC, which was well tolerated. No patients received maintenance BV. CONCLUSIONS : Gem/Bu/Mel without maintenance BV was safe and effective in patients with refractory or poor-risk relapsed HL, with comparable results to those from the AETHERA trial using BEAM and maintenance BV. A randomized trial is necessary to compare Gem/Bu/Mel and BEAM. Disclosures Off Label Use: Gemcitabine, busulfan and melphalan are not FDA approved at high doses for Hodgkin9s lymphoma. Alousi: Therakos, Inc: Research Funding. Andersson: Otsuka Research and Development, Inc.: Consultancy. Fanale: Merck: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity9s Board of Directors or advisory committees; Spectrum: Membership on an entity9s Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity9s Board of Directors or advisory committees; Amgen: Membership on an entity9s Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding.