Arai, Sally

Introduction: High dose chemotherapy and autologous stem cell transplantation (ASCT) is one of the most effective therapies in light chain (AL) amyloidosis. It is associated with a high hematologic response rate and leads to durable remissions. High dose melphalan is the most frequently used conditioning chemotherapy, as has been used in multiple myeloma (MM). Melphalan dose is based on renal function, age, degree of cardiac involvement and patients' frailty and is predictive of outcomes. While studies that assessed the conditioning schedule have been conducted in MM, with variable results, no such studies were done in AL amyloidosis. Methods: In this retrospective study, we explored the impact of the conditioning schedule on post-transplant outcomes in a large multicenter study. Patients with AL amyloidosis who underwent ASCT for the primary diagnosis of AL amyloidosis between January 1, 2003, and December 31, 2020, were included in this study. Results: One thousand seven hundred and eighteen (n=1718) patients from 9 centers are included. The median age was 58 years, and 61% were male. Most patients had one (43%) or two (33%) involved organs, with the most involved organs were the kidneys (69%) followed by the heart (52%). Induction therapy was given to 52% of patients. The conditioning regimen was almost exclusively melphalan (99.2%), with 65% receiving full dose melphalan (≥170 mg/m 2). Melphalan was given over two days in most patients (80%). A rest day between conditioning and stem cell infusion was provided in 53% of patients, mostly in those who received melphalan on a single day rather than over 2 days (87% vs 44%, P<0.001). Post-transplant hematologic response was available for 1569 patients (91% of patients) and were assessed from baseline. Complete response (CR) and very good partial responses (VGPR) were achieved post-ASCT in 33.7% of patients each. Low dFLC-partial response (PR) was achieved in 2.7% and PR in 18% of patients. Altogether, satisfactory post-ASCT response (CR, VGPR, or low-dFLC PR combined) was achieved in 70% of patients. Compared to no induction, less than a PR to induction was associated with a lower probability of achieving satisfactory post-ASCT response, while PR or better to induction had higher chances of satisfactory post-ASCT response (65% vs 46% vs 84%, P<0.001). A single day of melphalan conditioning was associated with a higher probability of satisfactory post-ASCT response compared to two days of conditioning (82% vs 67%, P<0.001). Omitting a day of rest between conditioning and stem cell infusion was also associated with higher satisfactory post-ASCT response compared to having a rest day (76% vs 65%, P<0.001). The Table lists other predictors for a post-ASCT satisfactory hematologic response. In a nominal multivariate logistic regression analysis, independent predictors for higher post-ASCT satisfactory hematological response rate included: PR or better to induction therapy, female gender, kappa light chain isotype, lower dFLC at baseline, and kidney and liver involvement. In addition, full dose melphalan, conditioning given over a single day and having no rest day between conditioning and stem cell infusion were also associated with a higher likelihood of satisfactory post-ASCT response. Post-ASCT hematologic CR rate was higher in those receiving full dose conditioning (36% vs 28%, P<0.001), in those having no rest day (40% vs 28%, P<0.001) but not in those who received one day of conditioning versus two days (35% vs 33%, P=0.5). The rate of ICU admission was higher in those receiving no day rest (17.7% vs 12.6%), P=0.003) and among those who received reduced dose melphalan (18.1% vs 13.3%, P=0.008) but not based on number of conditioning days (P=0.56). Day 100 mortality was significantly higher in the no rest day group (5.6% vs 3.2%, P=0.01) and among those receiving reduced dose melphalan (6.8% vs 3.1%, P=0.004) compared to their counterparts, but not based on the number of days of conditioning (P=0.89). The median follow-up in the entire cohort was 104 months (95% CI 98-110). In a multivariate analysis for overall survival (OS), the conditioning dose but not the conditioning schedule was independently associated with OS. Conclusions: This study is the first to demonstrate the effect of melphalan conditioning schedule on post-transplant response. This study supports a single day melphalan conditioning in AL amyloidosis to improve post-ASCT response.

Abstract In the pre–novel agent era, the median postprogression overall survival (PPS) of patients with classic Hodgkin lymphoma (cHL) who progress after autologous stem cell transplant (ASCT) was 2 to 3 years. Recently, checkpoint inhibitors (CPI) and brentuximab vedotin (BV) have improved the depth and durability of response in this population. Here, we report the estimate of PPS in patients with relapsed cHL after ASCT in the era of CPI and BV. In this multicenter retrospective study of 15 participating institutions, adult patients with relapsed cHL after ASCT were included. Study objective was postprogression overall survival (PPS), defined as the time from posttransplant progression to death or last follow-up. Of 1158 patients who underwent ASCT, 367 had progressive disease. Median age was 34 years (range, 27-46) and 192 were male. Median PPS was 114.57 months (95% confidence interval [CI], 91-not achieved) or 9.5 years. In multivariate analysis, increasing age, progression within 6 months, and pre-ASCT positive positron emission tomography scan were associated with inferior PPS. When adjusted for these features, patients who received CPI, but not BV, as first treatment for post-ASCT progression had significantly higher PPS than the no CPI/no BV group (hazard ratio, 3.5; 95% CI, 1.6-7.8; P = .001). Receipt of allogeneic SCT (Allo-SCT) did not improve PPS. In the era of novel agents, progressive cHL after ASCT had long survival that compares favorably with previous reports. Patients who receive CPI as first treatment for progression had higher PPS. Receipt to Allo-SCT was not associated with PPS in this population.

AbstractClinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant‐eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)‐based regimens before ASCT. Study endpoints included event‐free survival (EFS), progression‐free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI‐based regimens prior to ASCT. When adjusted for time to relapse, pre‐ASCT response and use of BV maintenance, patients receiving CPI‐based regimens had superior 2‐year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI‐based regimens were associated with superior 2‐year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03–0.5, p < .0001). OS did not differ by pre‐ASCT salvage regimen. In this large multicenter retrospective study, CPI‐based regimens improved EFS and PFS compared to other salvage regimens independent of pre‐ASCT response. These data support earlier sequencing of CPI‐based regimens in R/R cHL in the pre‐ASCT setting.

Abstract Background: MGTA-145, a CXCR2 agonist, has shown promising activity for hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical models and healthy volunteers. It has the potential to become the first GCSF free regimen for HSC mobilization/apheresis in preparation for transplant, with fewer side effects, better patient experience and optimal resource utilization. Methods: We conducted a single center phase 2 trial of MGTA-145 + plerixafor for HSC mobilization in patients with multiple myeloma (MM), NCT04552743. Primary endpoint was collection of ≥2 x 10 6 CD34+ cells/kg in up to 2 days of mobilization/apheresis. Secondary endpoints were collection of 4 and 6 x 10 6 CD34+ cells/kg, safety and engraftment. Patients with MM, 18-70 years of age, within 1 year of starting treatment & CrCl &gt; 30 ml/min were eligible. Patients received plerixafor 0.24 mg/kg (0.16 mg/kg if renal dysfunction) SQ, followed 2 hours later by MGTA-145 (0.03 mg/kg) IV over 3-10 minutes and apheresis within 30 minutes. Mobilization and collection were repeated for a second consecutive day if day 1 yield was &lt; 6 x 10 6 CD34+ cells/kg. The study was open-label single arm trial of 15 patients. If 13 or more patients met primary endpoint, an expansion cohort of 10 patients was planned. The trial has 85% power at a 5% one-sided type I error rate. Our analysis is based on aggregated results from total cohort of 25 patients. Results: Median age was 62 years, 52% were female, 24% had ISS stage 3, 57% had high-risk FISH (primarily gain1q). Induction therapy was VRD in 68% (17), daratumumab VRD in 24% (6), CyBorD in 8% (2) patients. Median duration of induction was 4 months (3-6) and median lenalidomide exposure was 5 cycles (1-8), with &gt; VGPR in 88% of patients. (Table 1) Plerixafor 0.24 mg/kg was given in 24 (96%) patients. Median pre-apheresis CD34 count was day 1, 24/uL (3-99) & day 2, 15/uL (5-46). Median total HSC cell yield (CD34+ cells/kg x 10 6) was 5.0 (1.1-16.2), day 1 yield was 3.4 (0.3-16.2) and day 2 yield was 1.9 (0.5-4.6) (Fig1). 88% (n=22) of patients met the primary endpoint of collecting sufficient HSCs in &lt; 2 days of mobilization + apheresis to proceed to transplant, 68% (17) in 1 day (2 x 10 6 CD34+ cells/kg). 3 patients who did not meet primary endpoint successfully collected HSCs with standard GCSF + plerixafor dosing & 2-3 apheresis sessions. Secondary endpoints of 4 and 6 x 10 6 CD34+ cells/kg in &lt; 2 days were met in 68% (17) and 40% (10) patients. MGTA-145+plerixafor was well tolerated. At least 1 treatment emergent AE (TEAE) with MGTA-145 was seen in 60% of patients (grade 1, n= 14, grade 2, n=1). Pain (all grade 1) was most common, seen in 44% (11), with 38% (9) patients experiencing acute onset transient bone pain with MGTA-145 (duration: 7 minutes, range: 3-28). Using the validated Brief Pain Inventory, 56% (14) patients self-reported pain with mobilization vs 40% (10) at baseline. 7/15 patients without baseline pain reported pain with mobilization. An increase for worst pain was seen on mobilization day 1, that returned to the baseline, but no difference for aggregate score of pain severity/interference (linear mixed effects model). At last follow-up, 18 patients have completed transplant with MGTA-145 mobilized graft, with melphalan 200 mg/m 2 in 15 (83%) patients. Median of 3.5 (2.2-8.1) x 10 6 CD34+ cells/kg were infused. All patients have engrafted. Median time to neutrophil engraftment of 12 days (range: 11-15) & platelet engraftment (platelets &gt; 20,000, no transfusion in 7 days) of 17.5 days (15-33) are comparable to historical data (DiPersio et al. 2009). RBC transfusion was needed in 3 (17%) patients. 14 patients have day 100 follow-up, all with durable engraftment. MGTA-145 + plerixafor mobilized grafts had a favorable graft composition. We observed high enrichment for CD90+CD45RA- among CD34+ cells, a CD34 subset of long term engrafting HSCs (median: 36% of CD34+ cells, range 10-66%, N=25). 74% (17 of 23) grafts were minimal residual disease negative with next generation flow cytometry. Conclusions: This is the first study to evaluate the novel G-CSF-free regimen of MGTA-145 + plerixafor for HSC cell mobilization & collection for hematologic malignancies. The study cohort was representative of transplant eligible patients with MM, with 88% patients meeting the primary endpoint. The regimen was well tolerated. Patients achieved timely & durable engraftment. Our data support further development of this regimen for rapid HSC mobilization. Figure 1 Figure 1. Disclosures Sidana: Janssen: Consultancy, Research Funding; Allogene: Research Funding; Magenta Therapeutics: Consultancy, Research Funding; BMS: Consultancy. Kumar: Bluebird Bio: Consultancy; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Oncopeptides: Consultancy; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy; Antengene: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Roche-Genentech: Consultancy, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Muffly: Pfizer, Amgen, Jazz, Medexus, Pfizer: Consultancy; Astellas, Jasper, Adaptive, Baxalta: Research Funding; Adaptive: Honoraria, Other: fees for non-CME/CE services: , Research Funding. Arai: Magenta Therapeutics: Research Funding. Meyer: Indee, Jura: Consultancy; Orca Biosystems: Research Funding; GigaImmune: Current holder of stock options in a privately-held company; Triursus Therapeutics: Current holder of stock options in a privately-held company. Rezvani: US Department of Justice: Consultancy; Kaleido: Other: One-time scientific advisory board; Nohla Therapeutics: Other: One-time scientific advisory board; Pharmacyclics-Abbvie: Research Funding. Weng: Kite Pharma: Research Funding. Frank: Kite-Gilead: Membership on an entity's Board of Directors or advisory committees; Allogene Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Shiraz: Kite Pharma-Gilead: Research Funding. Girgenti: Magenta Therapeutics: Current Employment. Goncalves: Magenta Therapeutics: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Schmelmer: Magenta Therapeutics: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Davis: Magenta Therapeutics: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Shizuru: Jasper Therapeutics, Inc.: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Chair of scientific advisory board; Forty seven Inc: Other: Inventor on a patent licenses by Forty Seven. Forty seven was acquired by Gilead in 2020. Miklos: Pharmacyclics: Patents & Royalties; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy; Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees.

Abstract Introduction: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) after autologous stem cell transplant (ASCT); yet studies comparing novel ST with conventional salvage chemotherapy are lacking. In a single center cohort, we demonstrated that bendamustine/brentuximab (BBV) had higher overall response rates (ORR) and complete response (CR) rates in ASCT-eligible R/R cHL (Desai et al JCO, 2021). Herein we report comparative outcomes of novel and conventional ST in R/R cHL who undergo ASCT, in a large multicenter retrospective cohort. Methods: Consecutive R/R cHL pts who underwent ASCT at 12 institutions across United States were included. Demographics and clinical variables at relapse including age, sex, B symptoms, stage, bulky disease (BD, single mass &gt; 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year) were recorded by electronic health records review. Study objectives were ORR, CR to first ST, post-ASCT PFS and OS by final ST. Time to event endpoints were defined from date of ASCT. Results: From 12 participating institutions, 853 pts of R/R cHL who underwent ASCT were eligible for this study. Median age was 33 (14-72) years, 457 (54%) were male, 446 (52%) had BD, 257 (30%) had advanced stage, 271 (32%) had END, 369 (43%) had B symptoms, 142 (17%) had PRD and 307 (36%) had ER. All 853 received at least 1 ST, 245 received 2 ST, 71 received 3 ST and 26 received 4 ST. Seven groups of ST were identified: 1. Conventional platinum-based chemotherapy (PBC) group including ICE, DHAP and ESHAP 2. BBV 3. Brentuximab Vedotin and nivolumab (BV/Nivo) 4. BV alone (BV) 5. gemcitabine-based chemotherapy (Gem) 6. checkpoint inhibitors (CPI) and 7. other miscellaneous agents (Misc). 1st ST was as follows: 553 had PBC; 69 had BBV; 48 had BV/Nivo; 65 had BV; 49 had Gem; 4 had CPI and 63 had Misc. There was no significant difference in the baseline characteristics by type of 1 st ST (data not shown). BBV had significantly higher ORR (92% vs 79%, p&lt;0.001) and CR rate (80% vs 49%, p &lt;0.001) compared to PBC. BV/Nivo had significantly higher CR rate (67% vs 49%, p &lt;0.001) and a trend towards higher ORR (86% vs 79%, p = 0.1) compared to PBC. BV had significantly lower ORR (62% vs 79%, p &lt;0.001) and CR rate (34% vs 49%, p &lt;0.001) compared to PBC. There was no difference in ORR and CR rate of PBC, Gem, CPI and Misc agents. Final ST prior to ASCT was PBC in 451, BBV in 76, BV/Nivo in 48, BV in 87, CPI in 24, Gem in 90 and Misc in 64. Table 1 lists K-M estimates of 2-year survival probabilities for different Final ST groups. Median follow up was 3 (range 0.1-13) years. BV/Nivo group had significantly higher proportion of patients with PRD and BD than PBC, no other differences in baseline characteristics were identified amongst ST groups (data not shown). BV/Nivo (HR: 0.1 (CI 95:0.02-0.4), p&lt;0.01) and CPI (HR: 0.12 (CI 95:0.03-0.5), p&lt;0.01) had significantly higher PFS than PBC. There was no significant difference in PFS between other ST groups (Figure 1a). Type of ST was not significantly associated with difference in OS (Figure 1b). 536 pts underwent ASCT in CR, 273 underwent ASCT in partial response (PR) and 31 underwent ASCT with progressive disease (PD). Pre-ASCT PR (HR 1.6 (CI 95:1.3-2.6), p&lt;0.001) and PD (HR: 4.1 (CI 95: 2.5-6.8), p&lt;0.001) predicted significantly lower PFS compared to CR (Figure 2a). OS was also significantly lower in pts with pre-ASCT PR (HR 1.7 (CI 95: 1.2-1.6), p&lt;0.001) and PD (HR 5.3 (CI 95: 2.8-10), p&lt;0.001) (Figure 2b). Higher number of pre-ASCT ST predicted lower PFS (HR 1.3 (CI 95: 1.1-1.6), p&lt;0.001) and OS (HR 1.5 (CI 95: 1.2-1.8), p&lt;0.001). In pts with pre-ASCT CR, all 36 who had pre-ASCT CR after BV/Nivo were alive and relapse free for follow up of 0.1-5 yrs. BV/Nivo was associated with significantly higher PFS (HR 0.1 (CI 95: 0.01-0.7), p &lt;0.05) but not OS compared to PBC in this subgroup. Increasing number of pre-ASCT ST predicted worse PFS (HR 1.5 (CI 95: 1.2-2.0), p&lt;0.01) and OS (HR 2.2 (CI 95: 1.4-3.4), p&lt;0.001) in this subgroup as well. Conclusions: BV/Nivo has a higher CR rate and better post-ASCT PFS compared to conventional chemotherapy and can lead to durable remissions in pts with pre-ASCT CR. BBV had a higher response rate and similar post-ASCT survival to conventional chemotherapy. BV had lower response rates compared to chemotherapy. Novel ST such as BV/Nivo and BBV may be preferable to conventional chemotherapy in R/R cHL. Figure 1 Figure 1. Disclosures Spinner: Notable Labs: Honoraria. Bachanova: FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; KaryoPharma: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dorritie: SITC presentation: Honoraria; Genmab: Research Funding; University of Pittsburgh/UPMC Hillman Cancer Center: Current Employment; Janssen: Research Funding; F. Hoffman-La Roche Ltd: Research Funding; Juno/BMS: Research Funding; Kite, a Gilead Company: Research Funding; OncLive/Institutional Perspectives on Cancer presentation: Honoraria. Arai: Magenta Therapeutics: Research Funding. Maurer: Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Diefenbach: Genentech, Inc./ F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; IMab: Research Funding; Morphosys: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding; Perlmutter Cancer Center at NYU Langone Health: Current Employment; AbbVie: Research Funding; IGM Biosciences: Research Funding; Incyte: Research Funding; Trillium: Research Funding; Gilead: Current equity holder in publicly-traded company; MEI: Consultancy, Research Funding. Nowakowski: Kyte Pharma: Consultancy; Ryvu Therapeutics: Consultancy; Selvita: Consultancy; Curis: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene/Bristol Myers Squibb: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MorphoSys: Consultancy; Bantham Pharmaceutical: Consultancy; Daiichi Sankyo: Consultancy; Zai Labolatory: Consultancy; Incyte: Consultancy; Kymera Therapeutics: Consultancy; TG Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Nanostrings: Research Funding. Advani: Astellas/Agensys: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees; Cell Medica: Membership on an entity's Board of Directors or advisory committees; Forty Seven: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutical: Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Kyowa: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Millenium: Research Funding; Pharmacyclics: Consultancy, Research Funding; Portola Pharmaceuticals: Consultancy; Regeneron: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees.

8023 Background: MGTA-145 (GroβT), a CXCR2 agonist, has shown promising activity for HSC mobilization with plerixafor in pre-clinical models and healthy volunteers. Methods: This phase 2 single center study evaluates HSC mobilization with MGTA-145 + plerixafor and same day apheresis in patients with multiple myeloma. Patients received plerixafor 0.24 mg/kg (0.16 mg/kg if renal dysfunction) SQ, followed 2 hours later by MGTA-145 (0.03 mg/kg) IV over 3-10 minutes and apheresis within 30 minutes. Mobilization was repeated for a second day if day 1 yield was < 6 x 106 CD34+ cells/kg. This interim analysis reports on mobilization in 10 patients (of 25 planned), including safety cohort of first 6 patients completing transplant. Primary endpoint is collection of 2 x 106 CD34+ cells/kg. Results: Median age was 63 years (range: 46-68), 50% were female, 22% had ISS stage 3 & 50% had high-risk FISH. Induction therapy was VRD in 7 and daratumumab + VRD in 3 patients; median induction duration: 4 months (3-6) & median lenalidomide exposure: 6 cycles (4-6), with > VGPR in 70%. Median total stem cell yield (CD34+ cells/kg x 106) was 7.1 (3-16.2), day 1 yield was 5.4 (1.1-16.2) & yield per apheresis session was 4 (1.1-16.2). 100% of patients met the primary endpoint of collecting sufficient HSCs in < 2 days of mobilization + apheresis to proceed to transplant (2 x 106 CD34+ cells/kg). Secondary endpoints of 4 and 6 x 106 CD34+ cells/kg in < 2 days were met in 90% & 80% patients. 30% patients underwent 1 apheresis, while 70% underwent 2 sessions. MGTA-145 was well tolerated. At least 1 adverse event (AE) was seen in 90% of patients, 20% had grade 2 AEs (anemia, hypokalemia) and 20% had grade 3 AEs (worsening of baseline grade 3 anemia; hypocalcemia); all resolved. Acute & transient bone pain was seen in 40% of patients (back-2, hip-1, sternum-1), all grade 1, all on day 1, & resolved without intervention after 6 minutes (3-10). All 6 patients in the safety cohort have completed transplant with melphalan 200 mg/m2. Median of 4.1 (3.4-5.6) x 106 CD34+ cells/kg were infused. All patients have engrafted timely (DiPersio Blood 2009); median time to neutrophil engraftment: 12 days (11-13) & platelet engraftment: 17 days (16-19). Apheresis graft analysis is available in these 6 patients. Grafts with MGTA-145+plerixafor showed high enrichment for CD90+CD45RA- among CD34+ cells, a CD34 subset of long term engrafting HSCs (median: 31% of CD34+ cells, 27-52), higher than seen with G-CSF (6%, Goncalves TCT 2021). 67% of grafts were minimal residual disease negative with next generation flow cytometry. Conclusions: This is the first study to evaluate the novel regimen of MGTA-145 + plerixafor for same day stem cell mobilization & collection in myeloma/hematologic malignancies, with 100% efficacy in interim analysis and the first to demonstrate successful engraftment in patients with cells collected with this GCSF free regimen. Clinical trial information: NCT04552743.

Abstract Introduction: Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand that can restore integrity to damaged intestinal mucosa in murine models of acute graft-versus-host disease (aGVHD). We previously described AREG as a circulating biomarker of late-onset aGVHD, but its relevance combined with clinical risk factors has not yet been tested in a large cohort of patients with aGVHD occurring prior to day 100 post-transplant. We therefore tested samples from two aGVHD first-line treatment trials, Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0302 and 0802, and identified a clinically relevant threshold level of circulating AREG at aGVHD onset. We then investigated whether incorporating AREG into the refined Minnesota Risk Score could further risk-stratify patients. Patients and Methods: Blood samples were obtained at the onset of systemic aGVHD treatment within BMT CTN 0302 (serum) and BMT CTN 0802 (plasma). All patients with response data and samples for analysis from both trials were included (N=251). We determined the association of AREG with clinical outcomes, including risk stratification by the refined Minnesota criteria, day 28 complete/partial response (CR/PR) to first-line therapy, 2-year overall survival (OS) and 6-month and 2-year non-relapse mortality (NRM). We investigated the effect of AREG on clinical endpoints per a doubling in the value of AREG, defined a clinically relevant threshold level in the AREG values using two-fold cross-validation, and confirmed the clinical relevance of this cut-point in independent samples (N=92) from pooled from drawn from the Chronic GVHD Consortium and the Mount Sinai Acute GVHD International Consortium (MAGIC). Results: In patients enrolled in BMT CTN 0302/0802, AREG levels were 1.7-fold higher in patients with Minnesota high-risk (HR) compared to standard-risk (SR) aGVHD (HR median 53.4 vs SR 31 pg/ml, p&lt;0.01). Every 2-fold increase in AREG was associated with a 33% decrease in the likelihood of day 28 CR/PR (odds ratio [OR] 0.67, p&lt;0.01, table). Clinical factors alone, as determined by the refined Minnesota Risk Score, were associated with day 28 CR/PR (p=0.02, table). Adding AREG to the Minnesota Risk Score could further risk-stratify patients. Minnesota SR patients with elevated AREG ≥ 33 pg/mL showed a 59% lower odds of day 28 CR/PR than SR patients with low AREG (OR 0.41, p=0.02). Patients with Minnesota HR aGVHD with AREG ≥ 33 pg/mL had the worst outcomes, with an 82% lower odds of day 28 CR/PR in comparison to HR with low AREG (OR 0.18, p&lt;0.01). High AREG was associated with worse OS and NRM in both Minnesota SR (hazard ratios 2-year OS 2.3, p&lt;0.01 and 6 month NRM 2.95, p=0.01, respectively) and HR patients (hazard ratios 2-year OS 3.35, p&lt;0.01 and 6-month NRM 9.38, p&lt;0.01 respectively, figure). Finally, in independent samples from the Chronic GVHD Consortium/MAGIC we confirmed that high AREG was associated with worse day 28 CR/PR (55.2% vs. 79.4%, p=0.02) and significantly worse 6-month survival after the onset of aGVHD (57.1% vs. 82.5%, p=0.01). Conclusion: AREG is elevated in patients with poor aGVHD outcomes and adds to the accuracy of risk stratification when combined with the refined Minnesota Risk Score. AREG ≥33 pg/mL at aGVHD onset is associated with lower day 28 CR/PR and higher mortality in samples from 4 multicenter cohorts. The mechanism of elevated circulating AREG in severe aGVHD is not yet known, although we hypothesize the degree of AREG elevation reflects the intensity of immune-mediated tissue injury resulting in AREG release. With accumulating evidence of altered EGFR ligands in aGVHD, further investigation into epithelial repair pathways involving AREG may lead to new adjunctive therapies to overcome poor steroid response in high-risk aGVHD. Disclosures Holtan: Incyte: Other: One-time advisory board member. Khera: Novartis: Consultancy. Lee: Mallinckrodt: Honoraria; Amgen: Other: One-time advisory board member; Bristol-Myers-Squibb: Other: One-time advisory board member; Kadmon: Other: One-time advisory board member. Chen: Immudex: Research Funding. Arora: Takeda Oncology: Consultancy. Flowers: Pharmacyclics: Consultancy. Cutler: Pfizer: Consultancy; Kite: Consultancy; Incyte: Consultancy; Bristol-Myers Squibb: Consultancy; Pharmacyclics: Consultancy; Astellas: Consultancy. Jagasia: Janssen: Consultancy, Research Funding; Therakos: Consultancy, Research Funding; Mallinckrodt: Consultancy. Hexner: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Levine: Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. MacMillan: Magenta Therapeutics: Research Funding.

Introduction: Anti-PD-1 monoclonal antibodies (mAbs) are highly active in relapsed/refractory classical Hodgkin lymphoma (cHL), but most patients (pts) will still relapse. Given this, allogeneic stem cell transplantation (alloHSCT) remains an important option for pts after PD-1 blockade, as it offers the possibility of cure. Prior reports have suggested that alloHSCT after PD-1 mAbs may be associated with severe immune-related complications including acute graft-versus-host disease (GVHD), veno-occlusive disease (VOD) and cytokine release/febrile non-infectious syndrome (CRS). Prior studies of alloHSCT after PD-1 blockade in cHL have been limited by the small number of pts and short follow-up, preventing an accurate assessment of long-term outcomes and complications, risk factors for early toxicity, and the impact of transplant strategies such as choice of GVHD prophylaxis. We therefore assembled a large retrospective international cohort of cHL pts who underwent alloHSCT after PD-(L)1 blockade to better answer these questions, including an assessment of the impact of post-transplant cyclophosphamide (PTCy) on efficacy and toxicity. Methods: Medical records and databases were reviewed at 26 European and United States transplant centers to identify pts with cHL who underwent an alloHSCT any time after receiving a PD-1 or PD-L1 mAb. Response assessment was performed by local investigators according to Lugano 2014 criteria. Overall survival (OS), progression-free survival (PFS), cumulative incidence (CumInc) of relapse (CIR), non-relapse mortality (NRM), acute (a) and chronic (c) GVHD were estimated, as was the association between baseline variables and these outcomes. Results: Between 2014 and 2019, 150 pts were identified who underwent alloHSCT after a median of 10 (range, 1-74) doses of nivolumab (n=118), pembrolizumab (n=31), or avelumab (n=1). The median age was 31 (range 17-68) and pts had received a median of 4 (range, 2-11) lines of therapy prior to PD-(L)1 blockade. 138 pts (92%) had failed BV and 111 (74%) autologous HSCT. The best overall response to PD-(L)1 mAbs was CR for 62 pts (41%), PR for 55 (37%), SD for 17 (11%), PD for 15 (10%) and unknown for 1 (1%). Median time from last dose of PD-(L)1 mAb to alloHSCT was 80 days (range, 17-756) with 70 pts (47%) receiving intervening systemic therapy. At alloHSCT, 90 pts were in CR (60%), 45 in PR (30%), 5 in SD (3%), and 10 in PD (7%). Donors were haploidentical (n=71, 47%), matched sibling (n=29, 19%), matched unrelated (n=39, 26%), mismatched unrelated (n=7, 5%), cord blood (n=2, 1%), or unknown (n=2, 1%). Stem cell source was bone marrow (n=38, 25%), peripheral blood (n=110, 73%), or cord blood (n=2, 1%). GVHD prophylaxis included PTCy in 88 pts (59%) (69/71 (97%) with haploidentical donors; 19/79 (24%) with other donors). With a median post-alloHSCT follow-up for survivors of 23.8 months (range, 1-67), the 2y OS and PFS were 79% (95CI 71-86%) and 65% (95CI 55-73%), respectively, while the 2y CumIncs of relapse and NRM were 21% (95CI 13-29%) and 14%, (95CI, 8-22%), respectively (Fig. 1A-B). 27 pts have died, 3 due to disease and 24 to NRM, including aGVHD (n=7) and VOD (n=2). Veno-occlusive disease (VOD) occurred in 5 pts (day 100 CumInc 4%) and 29 pts (19%) developed CRS (grade 1 n=16; grade 2 n=7; grade 3 n=4; grade 4 n=2). The 6-month CumIncs of grade 2-4, grade 3-4 and grade 4 aGVHD were 39%, 16% and 8%, respectively. Hyperacute GVHD (onset ≤ 14 days after alloHSCT) occurred in 4% of pts and was fatal in 2 pts. The 2y CumInc of cGVHD was 45%. Neither receipt of &gt; 10 doses (median) of anti-PD-(L)1 mAb nor undergoing alloHSCT ≤80 days (median) after last dose of PD-(L)1 mAb were associated with PFS or OS. However, pts with a shorter time to transplant (≤80 days) appeared to have a higher risk of severe (grade 3-4) aGVHD (6m CumInc 24% vs 9%, p=0.006). Recipients of PTCy in this cohort had lower 2y CumIncs of cGVHD (34% vs 58%, p=0.01) and relapse (12% vs 31%, p=0.02), superior 2y PFS (76% vs 54%, p=0.015), and similar rates of severe aGVHD (15% vs 18%, p=0.5), 2y NRM (12% vs 16%, p=0.5), and 2y OS (82% vs 78%, p=0.6). Conclusions: With extended follow-up of a large international cohort, our results argue that alloSCT performed after PD-(L)1 mAbs is a feasible strategy associated with an excellent PFS and a very low CIR for this disease. The use of PT-Cy appears to be associated with improved outcomes and may at present represent the optimal transplant strategy in this pt population. Figure Disclosures Corradini: kite: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Roche: Honoraria; Novartis: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Ho:Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Omeros Corporation: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Unum Therapeutics Inc.: Research Funding. Herrera:Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria. Hamadani:Pharmacyclics: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Merck: Research Funding; Otsuka: Research Funding; Janssen: Consultancy; Medimmune: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy. Ansell:LAM Therapeutics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding. Nieto:Astra-Zeneca: Research Funding; Affimed: Consultancy; Affimed: Research Funding; Novartis: Research Funding. Feldman:Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Pfizer: Research Funding; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Viracta: Research Funding; Trillium: Research Funding; Roche: Research Funding; Takeda: Honoraria, Speakers Bureau. McGuirk:ArticulateScience LLC: Other: Assistance with manuscript preparation; Bellicum Pharmaceuticals: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Stamatoulas Bastard:Celgene: Honoraria; Takeda: Consultancy. Houot:Bristol Myers Squibb: Honoraria; Merck Sharp Dohme: Honoraria. Manson:Bristol Myers Squibb: Honoraria. Orvain:Incyte: Honoraria; Novartis: Honoraria; Jazz Pharmaceuticals: Other: Travel & accommodations; Pfizer: Other: Travel & accommodations. Bouabdallah:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Frigault:Novartis: Consultancy; Kite/Gilead: Honoraria; Nkarta: Consultancy; Incyte: Consultancy; Juno/Celgene: Consultancy; Foundation Medicine: Consultancy; Xenetic: Consultancy. Chen:Takeda: Consultancy; Kiadis: Consultancy; Magenta: Consultancy; Abbvie: Consultancy; Incyte: Consultancy. Lynch:T.G. Therapeutics: Research Funding; Rhizen Pharmaceuticals S.A: Research Funding; Takeda Pharmaceuticals: Research Funding; Juno Therapeutics: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Smith:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Denovo Biopharma: Research Funding; Genentech: Research Funding; Ignyta (spouse): Research Funding; Incyte Corporation: Research Funding; Ayala (spouse): Research Funding; Seattle Genetics: Research Funding. Byrne:Karyopharm: Research Funding. Cohen:Hutchison: Research Funding; Astra Zeneca: Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Genentech, Inc.: Consultancy, Research Funding; UNUM: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; Lymphoma Research Foundation: Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Santoro:Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; BMS: Consultancy; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau. Armand:Sigma Tau: Research Funding; Otsuka: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Infinity: Consultancy; Genentech: Research Funding. Zinzani:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Carlo-Stella:Servier: Consultancy, Honoraria, Other: Travel, accommodations; Genenta Science srl: Consultancy; Boehringer Ingelheim: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Sanofi: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; AstraZeneca: Honoraria; Janssen Oncology: Honoraria; MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Takeda: Other: Travel, accommodations.