Session: 731. Clinical Autologous Transplantation: Results: Poster I
Hematology Disease Topics & Pathways:
Biological, therapy sequence, Diseases, Hodgkin Lymphoma, Therapies, Combinations, Lymphoid Malignancies, Clinically relevant, transplantation, stem cells
We retrospectively analyzed all pts with HRR HL treated at MDACC with HDC/ASCT between 1/1/2005-12/31/2019. HRR HL was defined by ≥1 of the modified AETHERA criteria: primary refractory disease, relapse within 1 year of completing initial therapy, extranodal extension at relapse, B symptoms at relapse, or requiring > 1 salvage therapy line. All pts underwent similar pre-SCT evaluation and met eligibility criteria as per our institutional guidelines. HDC regimens included BEAM, busulfan/melphalan (BuMel), GBM and SAHA/GBM. Post-ASCT consolidative radiotherapy (RT) was considered for bulky relapses and/or PET+ lesions at ASCT. We evaluated age, gender, ASCT year, primary refractory disease, prior disease-free interval (DFI), prior radiotherapy (RT), relapse within prior RT field, extranodal extension at relapse, B symptoms at relapse, bulky relapse (largest lesion >5 cm), No. prior relapses, No. prior lines of therapy, prior brentuximab vedotin (BV), prior anti-PD1, PET results at ASCT, post-ASCT maintenance BV and post-ASCT RT. Differences by regimen cohort were tested with Kruskal Wallis or chi-square tests. Outcomes were compared with the log-rank test. Univariable and multivariable Cox regression analyses evaluated factors associated with progression-free survival (PFS) and overall survival (OS).
A total of 501 pts, treated with BEAM (N=146), BuMel (N=38), GBM (N=189) and SAHA/GBM (N=128), were analyzed (Table 1). The GBM and SAHA/GBM cohorts had significantly more high-risk criteria (P=0.0006), with more pts with primary refractory disease (P=0.001) and bulky relapse (P<0.0001), as well as more pts with PET+ disease at ASCT (P=0.0002), and were slightly younger (P=0.04). Patient- and tumor-related variables did not change over time but there was a significant increase in prior BV (P<0.0001) and anti-PD1 (P<0.0001), a decrease in PET+ disease at ASCT (P=0.0008), and an increase in post-SCT BV (P<0.0001). BEAM and BuMel predominated earlier, GBM and BEAM in middle years, and SAHA/GBM and BEAM in later years (P<0.0001). Consequently, the SAHA/GBM cohort received more prior BV (P<0.0001) and anti-PD1 (P= 0.0001), and more post-ASCT BV (P<0.0001).
At a median follow-up of 50 months (6-186), 205 pts (40.9%) experienced relapse and 129 pts (25.8%) died. There were 2 ASCT-related deaths (both after BEAM) and 11 cases of t-MDS/AML (2 BuMel, 5 BEAM, 3 GBM and 1 SAHA/GBM). Outcomes improved significantly over time, with 2-year PFS/OS of 58%/82% (2004-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016-2019) (P<0.0001) (Fig. 1 and 2).
Multivariable analyses of PFS identified as independent favorable predictors: Prior BV (HR 0.61, P=0.03) and SAHA/GBM (GBM HR 1.24 compared to SAHA/GBM, BuMel HR 2.24, BEAM HR 2.26) (P=0.0003) (Fig. 3). The following were independent adverse PFS predictors: Primary refractory disease (HR 1.46, P=0.02), >2 prior lines (HR 1.51, P=0.04), bulky relapse (HR 1.45, P=0.01), B symptoms (HR 1.58, P=0.009), and PET+ at ASCT (HR 2.54, P<0.0001). Regarding OS, prior BV (HR 0.48, P=0.03) and SAHA/GBM (GBM: HR 1.55, BuMel: HR 5.08, BEAM: HR 5.31) (P<0.0001) (Fig. 4) were independent favorable predictors, whereas age >35 (HR 1.84, P=0.001), >2 prior lines (HR 1.89, P=0.01), B symptoms (HR 1.63, P=0.02), and PET+ (HR 2.24, P<0.0004) were adverse predictors. Post-SCT maintenance BV correlated with better PFS in univariate analyses (P=0.01) but did not retain significance in MVA (P=0.1).
The 5-yr PFS/OS rates were: S/GBM: 72/87%, GBM: 55/75%, BEAM: 45/61% and BuMel: 39/57%. These differences persisted both within the PET-negative (P=0.0002 / P<0.0001) and PET+ subgroups (P=0.002 / P<0.0001).
Outcomes of HRR HL pts have improved over the last 15 years. Incorporation of newer agents (BV and anti-PD1) to salvage therapy, resulting in more PET-negative CRs at ASCT, and the use of more active HDC regimens (especially, SAHA/GBM) were associated with these improved results.
Disclosures: Nieto: Novartis: Other: Grant Support; Affimed: Consultancy, Other: Grant Support; Secura Bio: Other: Grant Support; Astra Zeneca: Other: Grant Support. Hosing: NKARTA Inc.: Consultancy. Kebriaei: Amgen: Other: Research Support; Jazz: Consultancy; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Pfizer: Other: Served on advisory board. Popat: Bayer: Research Funding; Novartis: Research Funding. Qazilbash: Janssen: Research Funding; Bioline: Research Funding; Angiocrine: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy. Alousi: Therakos: Research Funding; Alexion: Honoraria; Incyte: Honoraria, Research Funding. Shpall: Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Rezvani: GemoAb: Membership on an entity's Board of Directors or advisory committees; Formula Pharma: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Other: Educational grant; Affimed: Other: Educational grant; Takeda: Other: Licensing agreement; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; Virogen: Membership on an entity's Board of Directors or advisory committees. Khouri: Pfizer: Research Funding; Bristol Myers Squibb: Research Funding. Ahmed: Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees. Parmar: Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Champlin: Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees; Cytonus: Consultancy; Actinium: Consultancy; Takeda: Patents & Royalties; Omeros: Consultancy; Johnson and Johnson: Consultancy.
OffLabel Disclosure: Vorinostat and busulfan were used as part of conditioning regimens for ASCT for Hodgkin lymphoma.
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