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Previous analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated effective antitumor activity and acceptable safety of pembrolizumab 200 mg given every 3 weeks for up to 35 cycles (~2 years) in patients with relapsed/refractory (R/R) primary mediastinal B-cell lymphoma (PMBCL) whose disease progressed after or who were ineligible for autologous stem cell transplantation. End points included objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR) by investigator per 2007 Response Criteria; overall survival (OS); and safety. In this final analysis, median duration of follow-up was 48.7 months (range, 41.2-56.2). ORR was 41.5% (complete response, 20.8%; partial response, 20.8%). Median DOR was not reached; no patients who achieved complete response had progressed at the data cutoff. Median PFS was 4.3 months; 4-year PFS rate was 33.0%. Median OS was 22.3 months; 4-year OS rate was 45.3%. At the data cutoff, 30 patients (56.6%) had any-grade treatment-related adverse events (AEs); the most common were neutropenia, asthenia, and hypothyroidism. Grade 3 or 4 treatment-related AEs occurred in 22.6% of patients; no grade 5 AEs occurred. After 4 years of follow-up, pembrolizumab continued to provide durable responses, with promising trends for long-term survival and acceptable safety in R/R PMBCL.

Here, we report the first comparative analysis of patient-reported outcomes (PROs) with chimeric antigen receptor T-cell therapy vs standard-of-care (SOC) therapy in second-line relapsed/refractory large B-cell lymphoma (R/R LBCL) from the pivotal randomized phase 3 ZUMA-7 study of axicabtagene ciloleucel (axi-cel) vs SOC. PRO instruments were administered at baseline, day 50, day 100, day 150, month 9, and every 3 months from randomization until 24 months or an event-free survival event. The quality of life (QoL) analysis set comprised patients with a baseline and ≥1 follow-up PRO completion. Prespecified hypotheses for Quality of Life Questionnaire-Core 30 (QLQ-C30) physical functioning, global health status/QoL, and EQ-5D-5L visual analog scale (VAS) were tested using mixed-effects models with repeated measures. Clinically meaningful changes were defined as 10 points for QLQ-C30 and 7 for EQ-5D-5L VAS. Among 359 patients, 296 (165 axi-cel, 131 SOC) met inclusion criteria for QoL analysis. At day 100, statistically significant and clinically meaningful differences in mean change of scores from baseline were observed favoring axi-cel over SOC for QLQ-C30 global health status/QoL (estimated difference 18.1 [95% confidence interval (CI), 12.3-23.9]), physical functioning (13.1 [95% CI, 8.0-18.2]), and EQ-5D-5L VAS (13.7 [95% CI, 8.5-18.8]; P < .0001 for all). At day 150, scores significantly favored axi-cel vs SOC for global health status/QoL (9.8 [95% CI, 2.6-17.0]; P = .0124) and EQ-5D-5L VAS (11.3 [95% CI, 5.4-17.1]; P = .0004). Axi-cel showed clinically meaningful improvements in QoL over SOC. Superior clinical outcomes and favorable patient experience with axi-cel should help inform treatment choices in second-line R/R LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03391466.

This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to 90Y-ibritumomab-tiuxetan 0.4 mCi/kg (arm A) vs. rituximab 375 mg/m2 every 8 weeks for 2 years (arm B). After a median follow-up of 10.55 years, 53 patients eventually progressed with a 10-year PFS of 50% vs. 56% for patients in arm A and B, respectively (HR = 1.42; p > 0.1). No significant differences were seen in OS (10-year OS 78% vs. 84.5%; HR = 1.39, p > .1). Patients receiving 90Y-ibritumomab-tiuxetan showed higher incidence of second neoplasms than those in arm B (10-year cumulative incidence 18.5 vs. 2%, respectively; p = .038). In conclusion, in FL patients responding to R-CHOP, no significant differences were found between consolidation and maintenance, although with higher late toxicity for consolidation.

Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses., This article provides real‐world European data on the results of relapsed/refractory large B‐cell lymphoma patients treated with tisagenlecleucel.

PURPOSE Romidepsin, a histone deacetylase inhibitor, has demonstrated activity in relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single agent. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used as first-line treatment of PTCL; however, it has limited efficacy. Results from a phase Ib and II study showed the feasibility of combining romidepsin with CHOP (Ro-CHOP). METHODS This study is a randomized phase III study of Ro-CHOP versus CHOP in adult patients with previously untreated PTCL. All patients received CHOP in 3-week cycles for six cycles. Romidepsin, 12 mg/m2, was administered intravenously over a 4-hour period on days 1 and 8 of each 3-week cycle for six cycles. The primary end point was progression-free survival (PFS) according to International Working Group 1999 criteria. RESULTS Between January 2013 and December 2017, 421 patients were enrolled (Ro-CHOP, n = 211; CHOP, n = 210). The median PFS for Ro-CHOP versus CHOP was 12.0 months (95% CI, 9.0 to 25.8) versus 10.2 months (95% CI, 7.4 to 13.2) with a hazard ratio of 0.81 ( P = .096). In the Ro-CHOP versus CHOP arms, the median overall survival was 51.8 versus 42.9 months and the objective response rate was 63% versus 60% with complete response plus unconfirmed complete response rates of 41% versus 37% ( P > .1 in all comparisons), respectively. Grade 3 or 4 treatment-emergent adverse events occurring in ≥ 30% of patients in the Ro-CHOP arm included thrombocytopenia (50% v 10% in the Ro-CHOP v CHOP arms, respectively), neutropenia (49% v 33%), anemia (47% v 17%), and leukopenia (32% v 20%). CONCLUSION The addition of romidepsin to CHOP did not improve PFS, response rates, nor overall survival and increased the frequency for grade ≥ 3 treatment-emergent adverse events. Ro-CHOP does not represent a significant advance in the standard of care for patients with previously untreated PTCL.

The search of prognostic factors is a priority in diffuse large B-cell lymphoma (DLBCL) due to its aggressiveness. We have recently found that the level of circulating MDSCs is a good marker of survival in a translational study based on a trial (EudraCT Number: 2014-001620-29), using lenalidomide combined with R-GDP (rituximab plus gemcitabine, cisplatin, and dexamethasone). Since Vitamin D is a known immunomodulator, we have studied blood levels of these cell populations comparing patients with deficit of vitamin D levels (&lt, 15 ng/mL with those with normal levels &gt, 15 ng/mL. Mann–Whitney U test was used to compare cells distributions between groups, Wilcoxon test to compare cells distribution at different times and Spearman test to measure the association between cell populations. Patients with vitamin D deficit maintained the increased level of immune suppressor cells, whereas we observed a depletion of all immune suppressor cells in patients with normal vitamin D levels. In conclusion, we have confirmed the importance of vitamin D in the response to treatment in R/R DLBCL, suggesting that vitamin D deficit may be involved in the immune deficit of these patients, and thus, vitamin D supplementation in these patients may help to obtain a better response, warranting further investigation.

Introduction Tisagenlecleucel (tisa-cel) is a second generation, CD19-targeted Chimeric Antigen Receptor (CAR) T-cell therapy for relapsed or refractory (R/R) large B-cell lymphoma (LBCL). The pivotal phase 2 trial JULIET included 93 patients and reported an overall response rate (ORR) of 52% and a complete response rate of 40% among treated patients. However, very little is known regarding its safety and efficacy in the commercial or real-world setting as well as from an intention-to-treat perspective. In our study, we report clinical outcomes of patients with R/R LBCL treated with commercial tisa-cel in 10 Spanish institutions. Methods Data were collected retrospectively from all consecutive patients with R/R LBCL who underwent apheresis for tisa-cel at a Spanish site from December 2018 until June 2020. Evaluable patients included those who received a CAR-T infusion and had at least 1 month of follow-up. Adverse events after infusion were graded according to the ASTCT consensus and efficacy outcomes were assessed according to the Lugano criteria. Efficacy outcomes were calculated in the patients who received a CAR T-cell infusion and in all patients who underwent apheresis for tisa-cel (intention-to-treat). Results During the study period 91 patients with R/R LBCL underwent apheresis for tisa-cel. At the study cutoff, 69 (76%) patients had received a CAR T-cell infusion whereas 22 (24%) had not due to progressive disease (n=10, 45%), pending manufacturing process (n=7, 32%), out of specification (OOS) or manufacturing failure (n=4, 18%), or others (n=1, 5%). Sixty-one patients had at least the first disease response evaluation at 1-month post-infusion. Baseline characteristics of the whole cohort and the infused patients are summarized in Table 1. Among infused patients, median age was 57 years (range 24-77) and 65% were male. Most of the patients had a high-risk International Prognostic Index score (62%), an advanced stage at diagnosis (91%) and were refractory to the previous therapy (80%). Median follow-up after CAR T-cell infusion was 4 months (1-16). Fifty-six patients (81%) received bridging therapy before infusion, including chemotherapy in most cases (n=51, 91%). All patients received fludarabine and cyclophosphamide as lymphodepleting chemotherapy. Median time from apheresis to infusion was 53 days (range 29-225). Median infused cell dose was 2.2 x 108 CAR positive viable T-cells (range 0.4-4.2 x 108). Eleven (16%) products were considered OOS although 45% of them were infused. Among the infused patients, 47 (68%) and 9 (13%) developed any grade of cytokine release syndrome (CRS) and neurotoxicity, respectively. Grade >2 CRS and neurotoxicity events occurred in 3 (4%) and 0 patients, respectively. Tocilizumab was administered to 21 (30%) patients and steroids to 13 (19%) patients. Nine (13%) patients required admission to the Intensive Care Unit. By day 100, 2 (3%) patients experienced non-relapse mortality. Other adverse events including infections and tumor lysis syndrome are summarized in table 2. Best response achieved among the infused patients included complete remission in 17 (28%) patients and partial remission in 22 (36%) patients, with an ORR of 64%. Stable disease and progressive disease were the best response in 4 (7%) and 18 (29%) patients, respectively. Considering all patients who underwent apheresis, CR and PR were obtained in 19% and 24% (ORR 43%), respectively. Median progression-free survival (PFS) and overall survival (OS) for infused patients were 3 months (95%CI 2.1-3.4) and 8 months (95%CI 5.7-10.8), respectively. In the univariate analysis, patients with ECOG score >1 (HR 4.3 95%CI 1.5 - 40.9) (p < 0.001) and IPI score >2 (HR 4.8 95%CI 1.6 - 14.4) (p = 0.002) were associated with lower PFS while an ECOG score >1 was also associated with lower OS (HR 3.4 95%CI 1.15 - 34.4) (p = 0.04). In the intention-to-treat analysis for all patients who underwent apheresis, median PFS and OS from apheresis were 4 months (95%CI 2.8-5.8) and 9 months (95%CI 5.8-11.8), respectively. Conclusions Treatment with tisa-cel was able to induce disease response with a good toxicity profile in a population of patients with LBCL treated in a European country. Poor performance status at the time of CAR T-cell infusion was associated with lower PFS and OS. Disclosures Iacoboni: Novartis, Gilead, Celgene, Roche: Honoraria. Guerreiro:Novartis: Honoraria. Mussetti:Novartis, Gilead: Honoraria, Research Funding. Sancho:Roche, Janssen, Celgene, Novartis, Gilead, Sandoz, Mundipharma y Takeda; Advisory y/o consultor para Roche, Janssen, Celgene, Novartis, Gilead, Sandoz, Celltrion y Kern-Pharma.: Honoraria. Hernani:Gilead: Honoraria. Sureda Balari:Takeda: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Consultancy; Celgene: Consultancy, Honoraria; BMS: Speakers Bureau; Roche: Honoraria. Martin Garcia-Sancho:Celgene, Eusa Pharma, Gilead, iQuone, Kyowa Kirin, Roche, Morphosys: Consultancy; Roche, Celgene, Janssen, Servier, Gilead: Honoraria. Kwon:Jazz: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Reguera:Celgene, Novartis: Consultancy; Novartis, Gilead: Honoraria. Barba:Novartis, Celgene, Gilead, Pfizer, Amgen, Roche: Honoraria.

7551 Background: Transplant-ineligible pts with R/R DLBCL have a poor prognosis (Gisselbrecht C, et al. Br J Haematol 2018). Several treatment options are available including platinum-based chemotherapies such as oxaliplatin plus rituximab and gemcitabine (R-GemOx). Adding polatuzumab vedotin to R-GemOx (Pola-R-GemOx) may improve outcomes for pts with a continued unmet medical need. The safety of polatuzumab vedotin and platinum-based therapy combinations must be considered as both are associated with neuropathy. POLARGO (NCT04182204; MO40598) is a Phase III, multicenter, open-label, randomized trial evaluating the safety and efficacy of Pola-R-GemOx vs R-GemOx in pts with R/R DLBCL. Methods: Results from the safety run-in stage of POLARGO are presented. The primary endpoint is the safety and tolerability of polatuzumab vedotin (1.8 mg/kg) + R-GemOx (R, 375 mg/m2; Gem, 1000 mg/m2; Ox, 100 mg/m2) given every 21 days for up to 8 cycles. Safety was assessed by the incidence, nature, and severity of adverse events (AEs; NCI CTCAE v5.0), with a focus on peripheral neuropathy (PN). Dose interruptions and reductions were used to assess tolerability. Granulocyte-colony stimulating factor was given as primary prophylaxis with each cycle (C) of therapy; anti-infective prophylaxis for pneumocystis and herpes virus was mandatory. Results: As of October 26, 2021, 15 pts were enrolled and 11 (73%) pts received ≥4 cycles of Pola-R-GemOx. Median age was 76 (range 47–87) years, 10 (67%) pts had an IPI score of 3–5, 7 (47%) had ≥2 prior therapy lines, and 8 (53%) were refractory to last treatment. Grade (Gr) 3–4 AEs were reported in 5 (33%) pts: thrombocytopenia (20%) and neutropenia (13%) were the most common. Two (13%) pts had serious AEs (Gr 3 febrile neutropenia and Gr 3 infection [n = 1 each]). There were no Gr 5 AEs or AEs leading to drug discontinuation. Eight (53%) pts had Gr 1 or 2 PN; there were no cases of Gr >3 PN. Three (20%) pts had drug interruptions due to PN. Two (13%) pts had a dose reduction of polatuzumab vedotin and oxaliplatin due to PN at C5 and C8, respectively; one pt (7%) had a dose reduction of polatuzumab vedotin due to Gr 4 thrombocytopenia at C2. End-of-treatment (EOT) objective response rate was 40% (95% CI: 16–68) and complete response rate was 27% (95% CI: 8–55); 7 (47%) pts had progressive disease at EOT. Ten (67%) pts received subsequent therapies following Pola-R-GemOx, including CAR-T cell therapy (n = 3) and stem-cell transplant (n = 1). Conclusions: In the safety run-in stage, Pola-R-GemOx was safe and tolerable. PN was manageable with dose interruptions and reductions; no cases of Gr ≥3 PN were observed. The toxicity of this combination did not compromise delivery of subsequent treatments. POLARGO is currently enrolling pts to receive Pola-R-GemOx vs R-GemOx; results will be presented at a future meeting. Clinical trial information: NCT04182204.

Introduction: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are the two autologous anti-CD19 chimeric antigen receptors T cells commercially approved in Europe for relapsed/refractory (R/R) DLBCL. We performed a retrospective study to evaluate patients characteristics, efficacy and safety for axi-cel and tisa-cel in a large cohort of patients within the GETH-TC (Spanish Group of Stem Transplantation and Cell Therapy)-GELTAMO (Spanish Group of Lymphoma and Autologous Stem Cell Transplantation). Methods: Ten Spanish centers contributed data. Data were collected retrospectively from consecutive patients with DLBCL in whom apheresis was performed for axi-cel or tisa-cel treatment. CRS and ICANS were graded with the ASTCT consensus criteria. Response was assessed according to the Lugano criteria. Patients included had at least 30 days of follow-up. Results: A total of 268 patients with R/R DLBCL underwent apheresis for axi-cel (n=123) and tisacel (n=145) from Nov-2018 to May-2021, of which 232 (86%) received CART-cell infusion (n=110, 89% and n=122, 84%, respectively). Reasons for not undergoing infusion were progression in 10 cases, tumor lysis syndrome in 1, infection in 1, and CR after bridging therapy in 1 for the axi-cel cohort, and progression in 21 (4 after manufacture failure), psychiatric disorder in 1, and post-apheresis cerebral hemorrhage in 1 case for the tisa-cel cohort. Time between apheresis and infusion was 41 days (IQR 40-56) and 49 days (IQR 46-62) (p=0.006), respectively. Characteristics at baseline, apheresis and at lymphodepletion are summarized in Tables 1 and 2. Median age was 60 (range 19-79), 61% of patients were male, most of them treated for DLBCL NOS (66%). There were no significant differences between patients intended to be treated with axi-cel and tisa-cel. 82% of the infused patients received bridging therapy. At apheresis and at lymphodepletion ECOG performance status score was 0-1 in 93% and 91%, and 7 and 32 patients were in response, respectively. The overall response rates (ORRs) at 1 month and 3 months were 65% and 56%, respectively, with 34% and 45% achieving a complete response (CR), respectively. In the intention-to-treat analysis, with a median follow-up of 9 months (IQR 5-15), EFS and OS at 9 months was 44% (95%CI 38-51)(Figure 1) and 59% (95%CI 53-66) with a median EFS and OS of 6 months and 11 months, respectively. At lymphodepletion, characteristics of infused patients and disease were not significantly different between axi-cel and tisa-cel cohorts. Rates of CRS, CRS grade 3-4, ICANS, ICANS grade 3-4 were 89% and 71% (p=0.001), 10% and 7% (p=0.34), 42% and 16% (p=0.001), 20% and 4% (p=0.001) for the axi-cel and tisa-cel cohorts, respectively. ICU admission was needed in 25% and 15% of patients (p=0.06), respectively. Non-relapse mortality at days 100 were 2.5% and 1.4%, and at day 180, 5.4% and 2.2% (p=0.08) for the axi-cel and tisa-cel groups, respectively. With a median follow-up of 8 months for patients who received infusion with axi-cel and 12 months for patients infused with tisa-cel, EFS and OS at 12 months were 48% and 33% (p=0.33), and 53% and 50% (p=0.27), respectively, with a median EFS of 11 and 6 months and a median OS of 13 and 12 months, respectively. In the multivariate analysis, the only factor associated with poor PFS was having ECOG-PS ≥2 at lymphodepletion (HR13, p=0.03). No factors were identified as associated independently to OS. Factors associated to CRS grade 3-4 were IPI score 4-5 at lymphodepletion (OR 1.4, p=0.03) and ECOG-PS ≥2 at apheresis (OR 1.5, p=0.03). For ICANS grade 3-4, factors associated were the use of axi-cel (OR 8, p=0.04) and diagnosis of HG double/triple hit lymphoma (OR 9, p=0.022). Conclusions:This multicentric analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe. Results are comparable to those from the pivotal studies and other large real-life experiences. Up to now, patients included for one or other product in Spain do not differ significantly in terms of baseline characteristics, and within this setting, results are comparable between both products in terms of efficacy. The use of axi-cel was associated to higher rates of CRS and especially, severe forms of ICANS. However, mortality associated to toxicity were low and not significantly different between both cohorts. Figure 1 Figure 1. Disclosures Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria. Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Reguera: Janssen, Kite/Gilead, Novartis: Speakers Bureau; BMS-Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees. Lopez Corral: Gilead, Novartis: Consultancy, Honoraria. Guerreiro: Novartis, Gilead: Consultancy, Honoraria. Caballero: Novartis, Gilead: Honoraria. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Sanchez: Janssen, Jazz Pharmaceuticals, Gilead, Novartis, Amgen: Consultancy. Sancho: Roche, Janssen, Celgene-BMS, Gilead, Novartis, Takeda: Honoraria, Speakers Bureau; Roche, Janssen, Celgene-BMS, Gilead, Novartis, Incyte, Beigene: Speakers Bureau. Bastos-Oreiro: Janssen: Honoraria, Speakers Bureau; F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Honoraria, Speakers Bureau; BMS-Celgene: Honoraria, Speakers Bureau; Gilead: Honoraria; Kite: Speakers Bureau. Oarbeascoa: Gilead: Honoraria, Speakers Bureau. Mussetti: Gilead: Other: Unspecified, Research Funding; Novartis: Honoraria, Other: Unspecified; Takeda: Honoraria. Bailen: Gilead, Pfizer: Speakers Bureau. Martin Garcia-Sancho: Takeda: Honoraria; Novartis: Consultancy; Incyte: Consultancy; Celgene/BMS: Consultancy; Celgene: Honoraria, Other: travel; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Janssen: Honoraria, Research Funding; Servier: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Gilead: Consultancy, Honoraria; Morphosys: Consultancy; Kyowa Kirin: Consultancy; Clinigen: Consultancy; Eusa Pharma: Consultancy; Kern Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Barba: Amgen, Celgene, Gilead, Incyte, Jazz Pharmaceuticals, MSD, Novartis, Pfizer and Roche, Jazz Phar,aceuticals: Honoraria; Cqrlos III heqlth Institute, aSOCIACION espanola contra el cancer, PERIS: Research Funding.

Introduction: Similar to classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma (PMBCL) expresses high level of the programmed cell death 1 (PD-1) ligands: PD-L1 and PD-L2. Prior analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated that monotherapy with the PD-1 inhibitor pembrolizumab had effective antitumor activity and acceptable safety in relapsed/refractory (R/R) PMBCL, leading to FDA approval for adult patients with R/R PMBCL after ≥2 prior therapies. Long-term durability of response with PD-1 blockade in patients with PMBCL, especially those who achieve complete remission (CR), remains a critical clinical question. Here we present updated efficacy and safety of patients with R/R PMBCL in KEYNOTE-170 after ~4 years of follow-up. Methods: Patients with R/R PMBCL who progressed after or were ineligible for autologous stem cell transplant and received ≥2 prior therapies received pembrolizumab 200 mg every 3 weeks (Q3W) for up to 35 cycles (~2 years). Response assessments were Q12W per 2007 Revised Response Criteria for Malignant Lymphomas. End points included overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR) by investigator assessment; as well as overall survival (OS) and safety. Data cutoff date was October 23, 2020. Results: At data cutoff, the median duration of follow-up was 48.7 months (range,41.2-56.2). Baseline characteristics of the patients have been previously described (Armand P, et al. J Clin Oncol. 2019; 37(34): 3291-3299). Among all treated patients (N=53), 13 completed 2 years of treatment and 40 patients discontinued, primarily due to progressive disease (n=18). ORR per investigator assessment was 41.5% (95% CI, 30.0-53.7), with 20.8% complete response rate and 20.8% partial response rate. Median DOR was not reached (NR) and 80.6% of patients had a response ≥48 months. Median PFS was 4.3 months (95% CI, 2.8-13.8) and the 48-month PFS rate was 33.0%. Median OS was 22.3 months (95% CI, 7.3-NR) and the 48-month OS rate was 45.3%. At data cutoff, treatment-related adverse events (AEs) of any grade occurred in 30 patients (56.6%); the most commonly reported (incidence >5%) were neutropenia (18.9%), asthenia (9.4%), hypothyroidism (7.5%), and fatigue and pyrexia (5.7% each). Grade 3-4 treatment-related AEs occurred in 22.6% of patients; only neutropenia (n=7) occurred in ≥2 patients. No grade 5 treatment-related AEs occurred. Conclusions: With 48.7 months of follow-up in heavily pretreated participants with R/R PMBCL, treatment with pembrolizumab monotherapy continued to demonstrate sustained antitumor activity. PFS and OS demonstrated promising trends for long-term survival with no new safety signals identified. Disclosures Zinzani: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Thieblemont: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Bouabdallah: Sandoz: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Abbvie: Honoraria; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Waleswski: Roche: Consultancy, Honoraria, Other: Institution: Research Grant/Funding; Takeda: Consultancy, Honoraria; Servier: Honoraria; Gilead: Consultancy, Honoraria; Amgen: Honoraria; Novartis: Consultancy, Honoraria; GSK/Novartis: Other: Institution: Research Grant/Funding; Abbvie: Consultancy, Honoraria. Fogliatto: AstraZeneca: Speakers Bureau. Martin Garcia-Sancho: Celgene: Honoraria, Other: travel; Celgene/BMS: Consultancy; Janssen: Honoraria, Research Funding; Servier: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Gilead: Consultancy, Honoraria; Morphosys: Consultancy; Kyowa Kirin: Consultancy; Clinigen: Consultancy; Eusa Pharma: Consultancy; Novartis: Consultancy; Takeda: Honoraria; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Incyte: Consultancy; Kern Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Christian: Celgene/BMS: Other: Institution: Research Grant/Funding; Acerta: Other: Institution: Research Grant/Funding; Seattle Genetics: Consultancy, Other: Institution: Research Grant/Funding; Genentech: Consultancy, Other: Institution: Research Grant/Funding; AstraZeneca: Consultancy; VeraStem: Consultancy; Morphosys: Consultancy, Other: Institution: Research Grant/Funding; Triphase: Other: Institution: Research Grant/Funding; Millenium: Other: Institution: Research Grant/Funding; Immunomedics: Other: Institution: Research Grant/Funding; Merck: Other: Institution: Research Grant/Funding. Özcan: Amgen: Honoraria, Other: Travel/Accommodations/Expenses; Janssen: Other: Travel/Accommodations/Expenses, Research Funding; Celgene: Research Funding; Archigen: Research Funding; Roche: Other: Travel/Accommodations/Expenses, Research Funding; Bayer: Research Funding; AstraZeneca: Research Funding; Takeda: Honoraria, Other: Travel/Accommodations/Expenses, Research Funding; Pfizer: Research Funding; BMS: Other: Travel/Accommodations/Expenses; Abbvie: Other: Travel/Accommodations/Expenses, Research Funding; Jazz: Other: Travel/Accommodations/Expenses; Abdi Ibrahim: Other: Travel/Accommodations/Expenses; Sanofi: Other: Travel/Accommodations/Expenses; MSD: Research Funding. Perini: Takeda: Speakers Bureau; Roche: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Abbvie: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau. Salles: Debiopharm: Consultancy; Incyte: Consultancy; Morphosys: Consultancy, Honoraria; Janssen: Consultancy; Epizyme: Consultancy, Honoraria; Rapt: Consultancy; Loxo: Consultancy; Ipsen: Consultancy; Miltneiy: Consultancy; Regeneron: Consultancy, Honoraria; Allogene: Consultancy; Velosbio: Consultancy; Takeda: Consultancy; Genmab: Consultancy; Genentech/Roche: Consultancy; Kite/Gilead: Consultancy; Novartis: Consultancy; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria. Shipp: Bayer: Other: Institution: Research Grant/Funding; AstraZeneca: Consultancy, Research Funding; Abbvie: Other: Institution: Research Grant/Funding; Immunitas Therapeutics: Consultancy; Merck: Research Funding; Bristol Myers Squibb: Research Funding. Thompson: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Chakraborty: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Marinello: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Armand: Merck: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Affimed: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Infinity: Consultancy; ADC Therapeutics: Consultancy; Celgene: Consultancy; Morphosys: Consultancy; Daiichi Sankyo: Consultancy; Miltenyi: Consultancy; Tessa: Consultancy; GenMab: Consultancy; C4: Consultancy; Enterome: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding; Otsuka: Research Funding; Sigma Tau: Research Funding; IGM: Research Funding; Kite: Research Funding.

Background: Immunochemotherapy induction followed by rituximab maintenance is the standard of care in previously untreated symptomatic follicular lymphoma (FL). The phase 3 RELEVANCE study of chemotherapy-free combination immunotherapy with lenalidomide and rituximab (R 2) showed promising activity comparable to standard rituximab + chemotherapy (R-chemo) options (Morschhauser, F and Fowler, NH, et al. N Engl J Med. 2018). Reported here are the results of the second interim analysis. Methods: RELEVANCE is a global, randomized, phase 3 trial (NCT01650701) of R 2 vs R-chemo followed by rituximab in patients with previously untreated grade 1-3a FL requiring therapy according to GELF criteria. Lenalidomide dose was 20 mg/d, d2-22/28 for 6-12 cycles (c), continued in responders at 10 mg/d for a total of 18 c. Rituximab dose was 375 mg/m 2 weekly c1 and d1 c2-6 and continued in responders for 12 additional c (q8wk). R-chemo was given per investigator's choice of standard R + cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), R + bendamustine (R-B), or R-CVP, followed by 12 c of rituximab (q8wk). Co-primary endpoints were complete response (CR)/CR unconfirmed (CRu) at 120 wk and progression-free survival (PFS) by independent review committee (IRC) based on 1999 IWG criteria. The prespecified second interim analysis was done after 75% of total PFS events were reached. Results: 1030 patients with high tumor burden were randomized to R 2 (n = 513) and R-chemo (n = 517; 72% R-CHOP, 23% R-B, 5% R-CVP); baseline characteristics were similar in both groups. As of October 30, 2020, at median follow-up of 72 mo, 6-year PFS, according to IRC assessment using FDA censoring rules, was 60% for R 2 and 59% for R-chemo with a hazard ratio (HR) of 1.03 (95% CI, 0.84-1.27). Data according to investigator assessment and EMA censoring rules are shown in the table. Median PFS was not reached for both groups. CR/CRu rates at 120 wk by IRC was 48% for R 2 and 53% for R-chemo (P = 0.10). Secondary endpoints, including overall survival, event free survival, and time to next antilymphoma treatment, were also similar in both groups. 162 (32%) R 2 and 166 (32%) R-chemo patients experienced progression/relapse according to investigator assessment of which 107 and 99 patients received additional treatment(s), respectively. Histological transformation was documented in 13/513 patients the R 2 group and 11/517 patients in the R-chemo group over the 72 mo follow-up period. ORR and overall survival after subsequent treatment(s) for relapse/progression were similar in both groups. The overall safety profile in both groups was consistent with the 1st interim analysis. The number of patients with second primary malignancies (SPMs) were similar between both groups, occurring in 57 (11%) R 2-treated and 67 (13%) R-chemo-treated safety population patients. The total number of SPMs was 64 in the R 2 group and 87 in the R-chemo group, with invasive SPM accounting for 43 (67%) and 52 (60%), respectively. Grade 5 adverse events were reported in 9 (2%) R 2 and 6 (1%) R-chemo treated patients. Conclusions: R 2 continues to demonstrate comparable efficacy vs R-chemo in patients with previously untreated grade 1-3a FL requiring therapy with similar 6-year PFS (60% and 59%) and 6-year OS (89% in both groups). Also, response and overall survival after subsequent treatment were similar in both groups. The overall safety profile of both groups was consistent with the previous analysis, with no new safety signals detected. R 2 provides a chemo-free alternative to R-chemo based on immunotherapy/immunomodulation. Figure 1 Figure 1. Disclosures Morschhauser: Chugai: Honoraria; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Genentech, Inc.: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees. Nastoupil: Bayer: Honoraria; Denovo Pharma: Other: DSMC; Gilead/Kite: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; MorphoSys: Honoraria; Caribou Biosciences: Research Funding; Genentech: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; IGM Biosciences: Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; Epizyme: Honoraria, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding. Feugier: Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Palomba: Wolters Kluwer: Patents & Royalties; Lygenesis: Honoraria; Pluto: Honoraria; Ceramedix: Honoraria; Priothera: Honoraria; Nektar: Honoraria; Novartis: Consultancy; Seres: Honoraria, Other: Stock, Patents & Royalties, Research Funding; Rheos: Honoraria; Magenta: Honoraria; Juno: Patents & Royalties; BeiGene: Consultancy; Kite: Consultancy; WindMIL: Honoraria; Notch: Honoraria, Other: Stock; PCYC: Consultancy. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Libby: Genentech: Research Funding; Janssen: Consultancy, Research Funding; BMS: Research Funding; GSK: Research Funding. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Flinn: Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Haioun: Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen-Cilag: Consultancy; Miltenyi Biotec: Consultancy; Takeda: Consultancy; Celgene: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead Sciences: Consultancy, Honoraria; Servier/Pfizer: Honoraria; Novartis: Honoraria. Ysebaert: Abbvie, AstraZeneca, Janssen, Roche: Other: Advisory Board, Research Funding. Bartlett: Celgene: Research Funding; Bristol Myers Squibb: Research Funding; Forty Seven: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; Merck: Research Funding; Millennium: Research Funding; Pharmacyclics: Research Funding; Autolus: Research Funding; Seagen: Consultancy, Research Funding; Roche/Genentech: Consultancy; ADC Therapeutics: Consultancy, Research Funding. Brice: MSD: Honoraria; BMS: Honoraria; Takeda: Consultancy, Honoraria, Research Funding. Ribrag: Nanostring: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding; Argen-X: Research Funding; Epizyme: Honoraria, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Martin Garcia-Sancho: Celgene: Honoraria, Other: travel; Celgene/BMS: Consultancy; Janssen: Honoraria, Research Funding; Incyte: Consultancy; Takeda: Honoraria; Novartis: Consultancy; Kern Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Eusa Pharma: Consultancy; Clinigen: Consultancy; Kyowa Kirin: Consultancy; Morphosys: Consultancy; Gilead: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Lopez-Guillermo: Roche, Gilead/Kite, Celgene, Novartis, Janssen, AbbVie, Spectrum: Consultancy, Honoraria, Research Funding. Larouche: Gilead: Consultancy. Ando: Astellas Pharma: Honoraria; Celgene: Honoraria; Chugai Pharmaceutical: Research Funding; Kyowa Kirin: Research Funding; Novartis: Honoraria; Takeda Pharmaceutical: Research Funding. Maria: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Astrazeneca: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). André: Johnson & Johnson: Research Funding; Roche: Other: Travel/accomodation/expenses, Research Funding; Incyte: Consultancy; Gilead: Consultancy, Other: Travel/Accommodations/Expenses; Karyopharm: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: Travel/Accommodations/Expenses; AbbVie: Other: Travel/accomodation/expenses; Celgene: Other: Travel/accomodation/expenses; Takeda: Consultancy, Research Funding. Sehn: Genmab: Consultancy; Novartis: Consultancy; Debiopharm: Consultancy. Izutsu: Takeda: Honoraria, Research Funding; Symbio: Honoraria; Solasia: Research Funding; Pfizer: Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; MSD: Research Funding; Kyowa Kirin: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Incyte: Research Funding; Huya Biosciences: Research Funding; Genmab: Honoraria, Research Funding; Fuji Film Toyama Chemical: Honoraria; Eisai: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Beigene: Research Funding; Bayer: Research Funding; AstraZeneca: Honoraria, Research Funding; Yakult: Research Funding; Allergan Japan: Honoraria; AbbVie: Honoraria. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Fowler: Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company. Salles: Velosbio: Consultancy; Epizyme: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Loxo: Consultancy; Regeneron: Consultancy, Honoraria; Novartis: Consultancy; Takeda: Consultancy; Incyte: Consultancy; Rapt: Consultancy; Kite/Gilead: Consultancy; Ipsen: Consultancy; Miltneiy: Consultancy; Genmab: Consultancy; Janssen: Consultancy; Genentech/Roche: Consultancy; Debiopharm: Consultancy; Allogene: Consultancy; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria.

Background: Outcomes are poor for patients with large B-cell lymphoma (LBCL) who relapse early or are refractory to first-line therapy. Furthermore, patients receiving second-line standard-of-care (SOC) therapy often report poor health-related quality of life (QoL; Lin V, et al. J Clin Oncol. 2020;38:e20070). In the ZUMA-7 (NCT03391466) pivotal Phase 3, randomized, open-label, multicenter study of axi-cel (an autologous anti-CD19 chimeric antigen receptor [CAR] T-cell therapy) versus SOC, we conducted the first comparative analysis of patient-reported outcomes (PROs) with CAR T-cell therapy versus SOC as second-line treatment in relapsed/refractory (R/R) LBCL. Methods: PRO instruments, including the EORTC QLQ-C30 (cancer-specific 30-item questionnaire including global health status, functional, and symptom scales) and the EQ-5D-5L (a general questionnaire with 5 QoL domains plus a global assessment), were administered at baseline (prior to treatment), Day 50, Day 100, Day 150, Month 9, and every 3 months from randomization up to 24 months or time of event-free survival event (disease progression, death from any cause, or new lymphoma therapy), whichever occurred first. The QoL analysis set was defined as all patients who had a baseline PRO and ≥1 measure completed at Day 50, Day 100, or Day 150. Prespecified hypotheses for 3 PRO domains (EORTC QLQ-C30 Physical Functioning, EORTC QLQ-C30 Global Health Status/QoL, and EQ-5D-5L visual analog scale [VAS]) were tested using a mixed-effect model with repeated measures at Day 100 and subsequent time points if previous time points were statistically significant. False Discovery Rate was used to adjust P values across key endpoints; sensitivity analyses were conducted to control for covariates and patterns of missingness. A clinically meaningful change was defined as 10 points for each EORTC QLQ-C30 score and 7 points for EQ-5D-5L VAS score. Exploratory analyses on other domains of EORTC QLQ-C30 and EQ-5D-5L were also performed. Results: Of 359 patients enrolled in the ZUMA-7 study, 296 patients (165 axi-cel, 131 SOC) had baseline PROs and ≥1 follow-up measure and were included for analysis. Overall, 70% of patients had primary refractory disease, 42% had high second-line age-adjusted International Prognostic Index (2-3), and 30% were ≥65 years old. For patients in the QoL analysis set treated with axi-cel versus SOC, there was a statistically significant (P Additional exploratory analyses of PRO endpoints (eg, EORTC QLQ-C30 role functioning, social functioning, fatigue, nausea/vomiting, dyspnea, insomnia, appetite loss, diarrhea, and EQ-5D-5L index [US value set]) also showed improvements with axi-cel over SOC. Conclusion: ZUMA-7, the first randomized, global, multicenter Phase 3 study of axi-cel versus SOC in second-line R/R LBCL, showed that treatment with axi-cel results in clinically meaningful improvement in QoL over SOC at Day 100 as measured by multiple validated PRO instruments. Score comparisons at later timepoints warrant cautious interpretation, particularly in the SOC arm, as attrition due to disease progression, new lymphoma therapy, or death may select patients with the best outcomes. The data also suggest faster recovery to pretreatment QoL with axi-cel compared with SOC. The superior clinical outcomes and patient experience with axi-cel over SOC should help inform treatment choices in second-line R/R LBCL. These data are reported on behalf of all ZUMA-7 investigators and contributing Kite members. Figure 1 Figure 1. Disclosures Elsawy: Kite, a Gilead Company: Consultancy, Honoraria; Celgene/BMS: Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy. Chavez: MorphoSys, AstraZeneca, BeiGene, Genentech, Kite, a Gilead Company, and Epizyme: Speakers Bureau; ADC Therapeutics: Consultancy, Research Funding; MorphoSys, Bayer, Karyopharm, Kite, a Gilead Company, Novartis, Janssen, AbbVie, TeneoBio, and Pfizer: Consultancy; AstraZeneca: Research Funding; BMS: Speakers Bureau; Merk: Research Funding. Avivi: Novartis: Speakers Bureau; Kite, a Gilead Company: Speakers Bureau. Larouche: Gilead: Consultancy. Wannesson: Novartis: Consultancy, Research Funding; MSD: Consultancy; BMS: Consultancy; AstraZeneca: Consultancy; Roche: Consultancy, Research Funding. Cwynarski: Kite, a Gilead Company: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Takeda: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Celgene: Consultancy; Atara: Consultancy; Gilead: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; BMS/Celgene: Other: travel to scientific conferences; Janssen: Consultancy, Other: travel to scientific conferences; Roche: Consultancy, Other: travel to scientific conferences, Speakers Bureau. Osman: Kite, a Gilead Company: Consultancy. Davison: Merck: Consultancy; AstraZeneca: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Gilead: Consultancy; Abbvie: Consultancy; Celegene: Consultancy. Rudzki: Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy; MSD: Consultancy; Roche: Consultancy, Speakers Bureau; BMS-Celgene: Consultancy. Dahiya: Jazz Pharmaceuticals: Research Funding; Miltenyi Biotech: Research Funding; Kite, a Gilead Company: Consultancy; Atara Biotherapeutics: Consultancy; BMS: Consultancy. Dorritie: OncLive/Institutional Perspectives on Cancer presentation: Honoraria; Janssen: Research Funding; University of Pittsburgh/UPMC Hillman Cancer Center: Current Employment; Juno/BMS: Research Funding; F. Hoffman-La Roche Ltd: Research Funding; Kite, a Gilead Company: Research Funding; Genmab: Research Funding; SITC presentation: Honoraria. Jaglowski: CRISPR Therapeutics: Consultancy; Takeda: Consultancy; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Radford: AstraZeneca: Current holder of individual stocks in a privately-held company; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Honoraria, Speakers Bureau; BMS: Honoraria. Morschhauser: Servier: Consultancy; Roche: Consultancy, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Janssen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees. Cunningham: AstraZeneca: Research Funding; Clovis Oncology: Research Funding; MedImmune: Research Funding; Roche: Research Funding; Celgene: Research Funding; Bayer: Research Funding; 4SC: Research Funding; Eli Lilly: Research Funding; OVIBIO: Membership on an entity's Board of Directors or advisory committees. Martin Garcia-Sancho: Kern Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Incyte: Consultancy; Takeda: Honoraria; Novartis: Consultancy; Eusa Pharma: Consultancy; Clinigen: Consultancy; Kyowa Kirin: Consultancy; Morphosys: Consultancy; Gilead: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Janssen: Honoraria, Research Funding; Celgene/BMS: Consultancy; Celgene: Honoraria, Other: travel; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Tzachanis: Partner: Consultancy; Takeda: Consultancy, Speakers Bureau; EUSA: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Kyowa Kirin: Consultancy; Magenta: Consultancy; Bristol Myers Squibb: Research Funding; Genentech: Research Funding; Incyte: Research Funding; Fate Therapeutics: Research Funding. Karmali: Roche: Consultancy; BMS/Celgene/Juno: Consultancy, Research Funding; EUSA: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Epizyme: Consultancy; Janssen/Pharmacyclics: Consultancy; AstraZeneca: Speakers Bureau; Genentech: Consultancy; Karyopharm: Consultancy; BeiGene: Consultancy, Speakers Bureau; Takeda: Research Funding. Kekre: Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Thieblemont: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Enblad: Kite, a Gilead Company: Consultancy; Gilead Sciences: Consultancy. Dreger: Riemser: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Bluebird Bio: Consultancy; Janssen: Consultancy; Gilead Sciences: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; BMS: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Malladi: Gilead: Honoraria, Other: Travel support; Gilead Science: Consultancy. Joshi: Open Health: Current Employment; Kite, a Gilead Company: Consultancy, Research Funding; various clients via employment: Consultancy, Research Funding. Wang: Kite, a Gilead Company: Consultancy, Research Funding; additional companies through employment with Open Health: Consultancy, Current Employment, Research Funding. Solem: OPEN Health: Current Employment; Kite, a Gilead Company: Consultancy; multiple clients through employment at OPEN Health: Research Funding. Thornton Snider: Kite, a Gilead Company: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Gilead: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. To: Kite, a Gilead Company: Current Employment, Other: stock or other ownership ; NantWorks: Ended employment in the past 24 months. Kersten: BMS/Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: Travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel support; Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support; Celgene: Research Funding; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding.

Introduction Brexucabtagene autoleucel (brexu-cel) is a second generation, CD19-targeted Chimeric Antigen Receptor (CAR) T-cell therapy approved for relapsed or refractory (R/R) mantle cell lymphoma (MCL). The pivotal phase 2 trial ZUMA-2 enrolled 74 patients and infused 68, with an overall response rate (ORR) of 85% (complete response rate, 59%) among all patients who underwent apheresis (intention-to-treat, ITT). Grade 3 or higher cytokine release syndrome (CRS) and neurologic events occurred in 15% and 31% of patients, respectively. However, very little is known regarding its safety and efficacy in the real-world setting. In our study, we report clinical outcomes of patients with R/R MCL treated with commercial brexu-cel. Methods Data were collected retrospectively from all consecutive patients with R/R MCL who underwent apheresis for brexu-cel at 7 European sites, in 3 different countries, from start of the Compassionate Use Program in Europe (February 2020) until June 2021. Evaluable patients included those who received a CAR-T infusion and had at least 1 month of follow-up. Adverse events after infusion were graded according to the ASTCT consensus and efficacy outcomes were assessed according to Lugano criteria. Efficacy outcomes were calculated in the patients who received a CAR T-cell infusion and in all patients who underwent apheresis for brexu-cel (ITT). Results During the study period 28 patients with R/R MCL underwent apheresis for brexu-cel. At data cutoff, 19 (68%) patients had received a CAR T-cell infusion whereas 9 (32%) had not due to progressive disease (n=4), pending manufacturing process (n=4) or achieving a complete response with bridging (n=1). Baseline characteristics of the whole cohort and the infused patients are summarized in Table 1. Among infused patients, median age was 67 years (range 51-78) and 89% were male. Most of the patients had a high-risk simplified Mantle Cell Lymphoma International Prognostic Index score (63%), an advanced stage (84%) and 32% had received a prior autologous stem cell transplant. Median follow-up after CAR T-cell infusion was 5 months (range 1-10). Fifteen patients (79%) received bridging therapy after apheresis, including ibrutinib in 8/15 (53%) patients, immunochemotherapy in 7/15 (47%) and radiotherapy in 6/15 (40%). Half the patients (53%) had progressive disease as best response to bridging; 4 (27%) patients had stable disease, 2 (13%) partial response and 1 (7%) achieved a complete response. Median time from apheresis to brexu-cel delivery was 30 days (range 22-48) and median time from apheresis to infusion was 42 days (range 28-77). Among the infused patients, 17 (89%) and 12 (63%) developed any grade of CRS and neurotoxicity, respectively. Grade >2 CRS and neurotoxicity events occurred in 1 (5%) and 5 (26%) patients, respectively. Tocilizumab was administered to 16 (84%) patients and steroids to 12 (63%) patients. Two (11%) patients required admission to the Intensive Care Unit for grade 4 neurotoxicity and septic shock, respectively. At data cutoff, all infused patients were alive except for 1 patient who died due to progressive disease. Other adverse events are summarized in table 2. Best response achieved among the infused patients included complete remission in 13 (68%) patients and partial remission in 4 (21%) patients, with an ORR of 89%. Stable disease and progressive disease were the best response in 1 (5%) patient each. Median progression-free survival (PFS) and overall survival (OS) for infused patients were not reached with the current follow-up (Figure 1); estimated 6-month OS was 91% (95%CI 50.8-98.6) and 6-month PFS was 83% (95%CI 55.4-94.2). Three (16%) patients progressed at days 14, 33 and 90 post-infusion. In the univariate analysis, the percentage of patients with complete response was consistent across key subgroups with high-risk features (including blastoid morphology and TP53 mutation). Response rate and survival analysis by ITT will be presented at the meeting when all products still undergoing manufacturing are complete. Conclusion This multicenter, international study confirms that treatment with brexu-cel in patients with R/R MCL in the real-world setting has very promising efficacy, including in high-risk patients. The early safety profile was manageable and similar to the pivotal trial. Longer follow-up is needed to better assess long-term efficacy and ITT analysis. Figure 1 Figure 1. Disclosures Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Chiappella: Takeda: Other: advisory board; Clinigen: Other: lecture fee, advisory board; Novartis: Other: lecture fee; Gilead Sciences: Other: lecture fee, advisory board; Janssen: Other: lecture fee, advisory board; Roche: Other: lecture fee, advisory board; Servier: Other: lecture fee; Celgene Bristol Myers Squibb: Other: lecture fee, advisory board; Astrazeneca: Other: lecture fee; Incyte: Other: lecture fee. Corral: Gileqd: Honoraria; Gilead: Consultancy; Novartis: Consultancy. Bastos-Oreiro: BMS-Celgene: Honoraria, Speakers Bureau; Gilead: Honoraria; Janssen: Honoraria, Speakers Bureau; F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Kite: Speakers Bureau. Schmidt: Novartis: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Kite/Gilead: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Takeda: Consultancy, Other: Travel, Accommodations, Expenses; BMS: Consultancy, Other: Travel, Accommodations, Expenses; Bayer Healthcare: Research Funding; Janssen: Other: Travel, Accommodations, Expenses. Carpio: Regeneron, TAKEDA, Celgene, Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travels and accommodation. Reguera: Janssen, Kite/Gilead, Novartis: Speakers Bureau; BMS-Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees. Kwon: Gilead: Honoraria. Martín García-Sancho: Janssen: Honoraria, Research Funding; Novartis: Consultancy; Gilead: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Zinzani: Beigene: Other, Speakers Bureau; MSD: Consultancy, Other: Advisory board, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; SANDOZ: Other: Advisory board; SERVIER: Other: Advisory board, Speakers Bureau; BMS: Other: Advisory board, Speakers Bureau; JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; GILEAD: Other: Advisory board, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; ADC Therap.: Other; Incyte: Other, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. Subklewe: Pfizer: Consultancy, Speakers Bureau; Janssen: Consultancy; Takeda: Speakers Bureau; Klinikum der Universität München: Current Employment; Gilead: Consultancy, Research Funding, Speakers Bureau; Miltenyi: Research Funding; MorphoSys: Research Funding; Novartis: Consultancy, Research Funding, Speakers Bureau; Roche: Research Funding; Seattle Genetics: Consultancy, Research Funding; BMS/Celgene: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau. Barba: Novartis: Honoraria; Pfizer: Honoraria; Gilead: Honoraria; BMS: Honoraria; Amgen: Honoraria.

Background: Peripheral T-cell lymphoma (PTCL) is an aggressive form of non-Hodgkin lymphoma (NHL) that is typically associated with a poor prognosis. Romidepsin is a histone deacetylase inhibitor approved by the US Food and Drug Administration for patients with PTCL who have received at least 1 prior therapy (J Clin Oncol. 2012;30:631). Presented here is the final analysis of a phase III randomized study comparing romidepsin + cyclophosphamide, doxorubicin, vincristine, and prednisone (Ro-CHOP) with CHOP in patients with previously untreated PTCL. Methods: Ro-CHOP (NCT01796002) is a randomized multicenter phase III study in adult patients with previously untreated PTCL (i.e. nodal or extranodal entities including primary cutaneous non epidermotropic TCL, with the exclusion of ALK-positive anaplastic large cell lymphomas and EBV-positive extranodal NK/T-cell lymphomas). Diagnostic biopsies were centrally reviewed (94%), and patients were randomized based on International Prognostic Index (IPI) score at baseline (< 2 vs ≥ 2), age (≤ 60 vs > 60 y), and histology type (nodal vs extranodal) to receive either Ro-CHOP or CHOP. Two-sided P-value from log-rank test stratified by all 3 stratification factors was used. All patients received CHOP in 3-week cycles for 6 cycles. Romidepsin, 12 mg/m2, was administered intravenously on days 1 and 8 of each 3-week cycle for 6 cycles (Lancet Haematol. 2015;2:e160), with dose reductions to 10 and 8 mg/m2 based on toxicity. The primary end point was progression-free survival (PFS) per Response Adjudication Committee assessment according to International Working Group 1999 criteria. Secondary end points included overall survival (OS), objective response rate (ORR), complete response (CR) + CR unconfirmed (CRu), and safety. Results: As of the December 13, 2019 cutoff date, 421 patients were included in the intention-to-treat population (Ro-CHOP, n = 211; and CHOP, n =210). Median age was 65 y (range, 25-81); 76 patients (18%) had ECOG PS of 2-3; 267 (63%) had Ann Arbor stage IV disease; and 342 (81%) had IPI score ≥ 2. At a median follow-up of 27.5 mo, the study did not meet its primary end point because Ro-CHOP did not show a statistically significant PFS improvement vs CHOP alone. Median PFS for Ro-CHOP vs CHOP was 12.0 mo (95% CI, 9.0-25.8) vs 10.2 mo (95% CI, 7.4-13.2), with a hazard ratio of 0.81 (95% CI, 0.63-1.04; P = 0.096). Median OS for Ro-CHOP vs CHOP was 51.8 mo (95% CI, 35.7-72.6) vs 42.9 mo (95% CI, 29.9-not evaluable). ORR of Ro-CHOP vs CHOP was 63% vs 60% with CR + CRu rates of 41% vs 37%. In the safety population (Ro-CHOP, n = 210; CHOP, n = 208), any-grade treatment emergent adverse events (TEAEs) that occurred ≥ 40% in the Ro-CHOP or CHOP arms, respectively, included anemia (67% vs 38%), nausea (55% vs 31%), thrombocytopenia (52% vs 17%), neutropenia (51% vs 37%), and vomiting (40% vs 10%). Grade 3/4 TEAEs that occurred in ≥ 30% of patients in the Ro-CHOP or CHOP arm, respectively, included thrombocytopenia (50% vs 10%), neutropenia (49% vs 33%), anemia (47% vs 17%), and leukopenia (32% vs 20%). One grade 5 TEAE occurred in the Ro-CHOP arm (E. coli sepsis), and 2 occurred in the CHOP arm (colitis and acute cholecystitis). In the Ro-CHOP vs CHOP arms, TEAEs led to CHOP dose interruption in 75 (36%) vs 42 (20%) patients, reduction in 54 (26%) vs 31 (15%) patients, and discontinuation in 7 (3%) and 6 (3%) patients, respectively. In the Ro-CHOP arm, TEAEs led to romidepsin interruption, reduction, and discontinuation in 132 (63%), 77 (37%), and 17 (8%) patients, respectively. Conclusions: The addition of romidepsin to CHOP did not improve PFS, the primary endpoint of the study, and response rates and OS appeared similar with the combination. The toxicity profile of Ro-CHOP was consistent with its phase Ib/II data, with no unexpected findings. The high rates of TEAEs with the addition of romidepsin hampered the ability to adequately administer 6 cycles of CHOP. Additional exploratory analyses to compare Ro-CHOP outcomes in specific patient subgroups are ongoing. The combination of CHOP plus romidepsin does not represent an advance in the standard of care for patients with previously untreated PTCL. Figure Disclosures Bachy: Beigene: Membership on an entity's Board of Directors or advisory committees; Roche, Gilead: Consultancy; Amgen: Research Funding; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria. Camus:PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); JANSSEN: Honoraria; AMGEN: Honoraria. Thieblemont:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Hospira: Research Funding; Incyte: Honoraria; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Bayer: Honoraria. Casasnovas:Amgen: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses, Research Funding; Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy, Honoraria. Ysebaert:Roche: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Guidez:BMS: Honoraria; CELGENE: Honoraria; TAKEDA: Honoraria; JANSEN: Honoraria; AMGEN: Honoraria; Service Hématologie et Thérapie cellulaire CHU POITIERS: Current Employment. Kim:JJ: Research Funding; Celltrion: Research Funding; Kyowa Kirn: Research Funding; Donga: Research Funding; Mundipharma: Research Funding; Pfizer: Research Funding; F. Hoffmann-La Roche: Research Funding. Lim:National Cancer Centre Singapore: Current Employment. André:Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Johnson & Johnson: Research Funding; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Novartis: Consultancy, Research Funding; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Takeda: Consultancy; Celgene: Other, Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy; Seattle Genetics: Consultancy. Martin Garcia-Sancho:Celgene, Eusa Pharma, Gilead, iQuone, Kyowa Kirin, Roche, Morphosys: Consultancy; Roche, Celgene, Janssen, Servier, Gilead: Honoraria. Penarrubia Ponce:Novartis: Consultancy; Takeda: Consultancy, Honoraria; Janssen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Servier: Honoraria; HOSPITAL CLINICO UNIVERSITARIO DE VALLADOLID: Current Employment; Abbvie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy; Celgene: Consultancy, Honoraria; Incyte: Consultancy. Staber:msd: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Celgene/ BMS: Consultancy, Honoraria. Trotman:BeiGene: Research Funding; Takeda: Research Funding; F. Hoffmann-La Roche: Research Funding; Celgene: Research Funding; PCYC: Research Funding. Hüttmann:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Other: Travel expenses; University Hospital Essen, University of Duisburg-Essen, Essen, Germany: Current Employment; Seattle Genetics: Research Funding; Lead Discovery Center GmbH: Consultancy; Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Honoraria. Gaulard:Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); INNATE PHARMA: Research Funding; TAKEDA: Consultancy, Honoraria, Research Funding; CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris: Current Employment. Delfau-Larue:MUNDIPHARMA: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); ROCHE: Honoraria; GILEAD: Honoraria; AMGEN: Honoraria. De Leval:Lausanne University Hospital & Lausanne University Institute of Pathology: Current Employment; Lunaphore Technologies SA: Consultancy, Honoraria; Abbvie: Honoraria; Roche Diagnostics: Honoraria. Meignan:ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Li:BMS: Current Employment, Current equity holder in publicly-traded company. Morschhauser:F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Servier: Consultancy. Delarue:Celgene International, a BMS company: Current Employment; BMS: Current equity holder in private company. OffLabel Disclosure: Romidepsin is not approved for patients with previously untreated PTCL.

Background: Mantle cell lymphoma (MCL) accounts for approximately 5-7% of non-Hodgkin lymphomas (NHL). Bruton's tyrosine kinase (BTK) inhibitors, eg ibrutinib, are indicated for treatment of adults with MCL who have received ≥1 prior therapy. Primary and acquired resistance to ibrutinib is common and linked with poor outcomes, and remains an unmet medical need. Parsaclisib, a potent, highly-selective, next-generation PI3Kδ inhibitor, demonstrated clinical activity in patients (pts) with relapsed or refractory (R/R) NHL. We report preliminary results for parsaclisib monotherapy in a cohort of pts with R/R MCL who were previously treated with ibrutinib in the open-label, phase 2 study CITADEL-205 (NCT03235544). Methods: Pts must be ≥18 years of age with pathologically confirmed MCL, R/R disease to the most recent treatment, documented cyclin D1 overexpression or t(11;14) translocation, have Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, and received 1 to 3 prior systemic treatments (including ibrutinib). Prior treatment with PI3Ki was prohibited. Pts were allocated to receive parsaclisib 20 mg once daily (QD) for 8 weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg QD (daily-dosing group [DG]). Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was required. Objective response rate (ORR) was the primary endpoint; complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability were secondary endpoints. All radiology-based endpoints were based on independent review. Results: From October 2017 to January 17, 2020 (data cut-off), 47 pts were treated (WG, n = 12; DG, n = 35). Enrollment is ongoing. At cut-off, 70% of pts had discontinued treatment, most commonly due to progressive disease (62%). Median exposure (range) was 2.2 (0.1-18.0) months. Median age was 70 years and 79% of pts were men. Median time since initial diagnosis was 4.7 years. Most pts (85%) had ECOG PS ≤1 and 51% had high-risk MCL International Prognostic Index. The median number of prior systemic therapies was 3; 38% of pts had prior hematopoietic stem cell transplant, and 38% were refractory to most recent systemic therapy. At data cut-off, 46 pts were evaluable for efficacy, including 12 in WG and 34 in DG (Table). Median follow-up (range) for this population was 10.2 months (1.5-25.9) overall and 7.6 months (1.5-25.9) for DG. ORR (95% confidence interval [CI]) and CRR were 28.3% (16.0-43.5) and 2.2%, respectively in all evaluable pts, and 35.3% (19.7-53.5) and 2.9%, respectively in DG. Median time to complete or partial response was 7.6 weeks. Median DOR (95% CI) was 7.3 months (0.2-not estimable) among all responders and 3.7 months (0.2-7.3) for DG. Median PFS (95% CI) was 3.65 months (1.9-3.9) overall and 3.65 months (1.9-5.5) for DG. Among 47 safety-evaluable pts, most common treatment-emergent adverse events (TEAEs) occurring in >10% of pts were anemia (19.1%), diarrhea (19.1%), neutropenia (14.9%), asthenia and cough (12.8% each), decreased appetite, dyspnea, fatigue, pyrexia and rash (10.6% each). Most common grade ≥3 TEAEs reported in ≥5% of pts included anemia (12.8%), neutropenia (10.6%), thrombocytopenia and rash (6.4% each). TEAEs leading to dose interruption or reduction occurred in 31.9% and 2.1% of pts, respectively. TEAEs leading to treatment discontinuation occurred in 2 (4.3%) pts (diarrhea and colitis). Serious TEAEs reported in ≥2 pts were diarrhea, dyspnea, peripheral swelling and pneumonia (4.3% each). Two pts experienced fatal TEAEs (one pt had general physical health deterioration and respiratory tract infection, deemed not related to treatment; one pt had pneumonia, neutropenia, and septic shock, deemed related to treatment and disease progression). New or worsening grade ≥3 laboratory test values of clinical interest occurring in ≥5% of pts included decreased neutrophils (14.9%), platelets (10.6%), and hemoglobin (8.5%); there were no grade ≥3 increases in alanine/aspartate aminotransferase. Conclusion: Preliminary efficacy data indicate that parsaclisib monotherapy is clinically active in this difficult-to-treat patient population. Treatment with parsaclisib had an acceptable safety profile and was generally well tolerated. Updated study results will be presented. Disclosures Zinzani: EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, 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; Janssen: Consultancy, Honoraria, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Eusapharma: Consultancy, Speakers Bureau. Delwail:Amgen: Consultancy. Paneesha:Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Janssen: Honoraria; AbbVie: Honoraria. Rule:AstraZeneca: Consultancy; Celgene: Consultancy; Celltrion: Consultancy; Janssen Oncology: Consultancy, Research Funding, Speakers Bureau; Roche Pharma AG: Consultancy, Research Funding. Martin Garcia-Sancho:Roche, Celgene, Janssen, Servier, Gilead: Honoraria; Celgene, Eusa Pharma, Gilead, iQuone, Kyowa Kirin, Roche, Morphosys: Consultancy. Salles:Amgen: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Gilead Sciences: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Servier: Consultancy, Honoraria; Acerta Pharma: Consultancy; Kite Pharma: Consultancy; Merck: Consultancy, Research Funding; Novimmune: Consultancy; Pfizer: Consultancy; Sanofi: Other. Sancho:Sandoz: Consultancy; Celltrion: Consultancy; Roche: Consultancy, Honoraria; Takeda: Honoraria; Novartis: Consultancy, Honoraria; Kern-Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria. Zheng:Incyte: Current Employment, Current equity holder in publicly-traded company. DeMarini:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Jiang:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Mehta:Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gelgene/BMS: Research Funding; Affimed: Research Funding; Merck: Research Funding; Kite/Gilead: Research Funding; Juno Parmaceuticals/BMS: Research Funding; Innate Pharmaceuticals: Research Funding; Oncotartis: Research Funding; Roche-Genentech: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; fortyseven Inc/Gilead: Research Funding; Takeda: Research Funding.

BACKGROUND Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), non-candidates for autologous stem-cell transplantation (ASCT), have few treatment options. Ibrutinib is an oral Bruton's tyrosine kinase inhibitor that has shown increased antitumor activity in patients with DLBCL of different subtype from germinal center B-cell like (non-GCB). In the present phase II clinical trial (NCT02692248), we investigated the efficacy and toxicity of the combination of Ibrutinib with the R-GEMOX-D regimen (rituximab, gemcitabine, oxaliplatin and dexamethasone), in patients with non- GCB DLBCL. METHODS We included patients with histological diagnosis of non-GCB DLBCL (according to Hans algorithm), with relapsed or refractory disease after at least 1 line of immunochemotherapy and non-candidates for ASCT. Patients received an induction treatment consisting of 6 (in case of complete remission [CR] after cycle 4) or 8 (in case of partial response [PR] or stable disease after cycle 4) cycles of R-GEMOX-D at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles, and the secondary objectives were: CR rate, progression-free survival (PFS), overall survival (OS) and toxicity. Analyses were performed in the intention to treat population (data cut-off 10th April 2020). RESULTS Sixty-four patients (59.4% male) were included between March 2016 and November 2018. Median age was 67 (25-84) years. Patients had received a median of 2 previous lines of treatment; 56.3% were refractory ( Of the 64 patients who started study treatment, 44 and 35 patients, respectively, were evaluated for response after 4th cycle and at the end of induction. Twenty-four (37%) patients started maintenance with ibrutinib, 7 of whom continue or have completed it. Causes of withdrawal from the trial (n=57) were progression (n=40), adverse event (n=6), transplantation (n=5), withdrawal of consent (n=3) and other causes (n=3). ORR and CR rate after 4th cycle were 53.2% and 35.9%, respectively. Patients with relapsed disease had significantly higher ORR (67.9% vs 41.7%, p=0.037) and CR rate (57.1% vs 19.4%, p=0.002) than patients with refractory disease. At the end of induction, ORR and CR rate were 35.9% and 29.7%, respectively. After a median follow-up of 22 months (range: 1 to 39 months), the estimated 2-year PFS and OS were 21% and 25%, respectively (Figure 1A and 1B), being significantly better in patients with relapsed disease (Figure 1C and 1D). In the multivariate analysis, status of lymphoma at study entry significantly influenced PFS (HR 0.45; 95% CI 0.25-0.82; p=0.009) and OS (HR 0.51; 95% CI 0.27-0.94; p=0.0031) independently from the IPI and the number of previous treatment lines. The most frequent adverse events (AE) (present in at least 20% of patients) were thrombocytopenia (67.2%), diarrhea (51.6%), neutropenia (46.9%), anemia (37.5%), fatigue (34.4%), nausea (29.7%) and paresthesia (20.3%). The most frequent grade 3-5 AE (present in at least 10% of patients) were thrombocytopenia (46.9%), neutropenia (35.9%), diarrhea (15.6%) and anemia (14.1%). Three patients presented a grade 5 AE, two of them related (aspergillosis and pneumonia, respectively) and one unrelated (heart failure). CONCLUSIONS The combination of ibrutinib with R-GEMOX-D as salvage therapy for patients with non-GCB DLBCL is associated with high response rates, especially in relapsed patients. The vast majority of refractory patients progress very early, so this regimen could be considered as a bridge to other consolidation therapies. Biological studies analyzing cell of origin by gene expression profiling, minimal residual disease and mutational spectrum are in progress. Disclosures Abrisqueta: Roche: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau. Giné:Janssen: Research Funding; Gilead: Research Funding; Roche: Research Funding. Grande:Janssen: Research Funding. Caballero:Roche: Other: travel; Gilead: Other: travel; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel; BMS: Other: travel; Takeda: Other: travel; Kite: Membership on an entity's Board of Directors or advisory committees. Martin Garcia-Sancho:Roche, Celgene, Janssen, Servier, Gilead: Honoraria; Celgene, Eusa Pharma, Gilead, iQuone, Kyowa Kirin, Roche, Morphosys: Consultancy. OffLabel Disclosure: Off-label use of a new combination in the context of a clinical trial. New combination (Ibrutinib + R-GEMOX)

Context: Outcomes of patients with transformed lymphoma have historically been poor, prompting many centres to include stem-cell transplant (SCT) as part of the treatment strategy. However, several studies in the rituximab era suggest that survival may be more favourable than previously recognized, questioning the need for such intensive therapies. Objective: We analyzed the efficacy of SCT in transformed lymphomas at a single reference Transplant Unit. Design: We collected data from 51 patients; the indication was a diagnosis of diffuse large B-cell lymphoma (DLBCL) transformed from an indolent lymphoma, from 1995 to 2018. Of them, 36 received an auto-SCT and 15 an allo-SCT. Results: Median age was 60 (range, 40-69) and 52 (range, 35-65) years for patients receiving auto-SCT and allo-SCT, respectively. Patients in the allo-SCT group had been more intensively pretreated, as 13 (87%) patients received >3 lines of treatment before SCT and 13 (87%) underwent a previous auto-SCT, whereas patients in the auto-SCT group were pretreated with a median of 2 (range, 1 to 4) lines of treatment. Regarding disease status at transplant, most patients (78% and 73% in the auto and allo-SCT groups, respectively) were transplanted in complete remission (CR). All auto-SCT patients received BEAM as conditioning regimen, whereas patients in the allo-SCT group received several fludarabine-based combinations. Transplant-related mortality (TRM) was 3.2% and 27% in the auto and allo-SCT groups, respectively. With a median follow-up of 61 and 50 months,4-year overall survival (OS) and progression-free-survival (PFS) were 87% and 76%, for the auto-SCT patients, and 52% and 56%, respectively, for the allo-SCT patients. In the auto-SCT group, 12 (33%) patients experienced disease progression and 7 (19.5%) died (5 [13.9%] from lymphoma), whereas in the allo-SCT group, only 2 (13%) patients had disease progression but 4 (27%) died due to transplant-related causes. Conclusions: SCT is a potentially curative option for patients with transformed lymphoma, since more than a half of patients are long-term survivors. Progression is the major cause of failure in auto-SCT whereas allo-SCT patients died because of toxicity. Efforts need to be made to identify patients who do not benefit from auto-SCT to avoid toxicity.

7500Background: Immunochemotherapy induction followed by rituximab maintenance is the standard of care in previously untreated symptomatic FL. Phase II studies of chemo-free combination immunotherapy with lenalidomide and rituximab (R2) show promising activity. Methods: RELEVANCE is a global, randomized, phase III trial (NCT01650701) of R2 vs R-chemo followed by rituximab in previously untreated grade 1-3a FL patients requiring therapy according to GELF criteria. Lenalidomide dose was 20 mg/d, d2-22/28 for 6-12 cycles (c), continued in responders at 10 mg/d for a total of 18 c. Rituximab dose was 375 mg/m2 weekly c1 and d1 c2-6 and continued in responders for 12 additional c (q8wk). R-chemo was given per investigator’s choice of standard R-CHOP, R-bendamustine (R-B), or R-CVP, followed by 12 c of rituximab (q8wk). Co-primary endpoints of CR/CRu at 120 wk and PFS (50% interim analysis by 1999 IWG) are reported here. Results: As of 31May2017, 1030 patients with high tumor burden were randomized to R2 (n = 5...

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma with diverse clinical, pathological and genetic features. An 80-year-old woman was diagnosed with a stage IV-X-A (Ann Arbor staging system) low grade systemic follicular lymphoma (FL). Four months after the diagnosis, she developed asymptomatic, indurated, annular erythematous plaques with centrifugal growth on the abdomen, arms and neck. The skin biopsy revealed a dermal infiltration compatible with diffuse large B-cell lymphoma. Light chain restriction by flow cytometry was demonstrated. The variable, diverse and joining genes of immunoglobulin G heavy chains were sequenced and cloned, and showed the same pattern for both the initial follicular lymphoma and the skin infiltration. Translocation t (14;18) was present in both samples. Based on these findings, a diagnosis of transformation of follicular lymphoma into diffuse large B cell lymphoma was made. Although other hematological disorders such as primary cutaneous diffuse large B cell lymphoma, mycosis fungoides and the cutaneous infiltration of chronic juvenile myeloid leukemia can present as annular lesions, we were unable to find any previous reports of these as a manifestation of cutaneous infiltration by systemic non-Hodgkin lymphoma.

Abstract 3 In elderly pts with newly diagnosed MM, the VISTA trial has demonstrated that the combination of bortezomib plus melphalan – prednisone (VMP) is significantly superior to MP alone. However, it remains to be elucidated which agent is the optimal partner for bortezomib: an alkylating agent or an immunomodulatory drug. In order to answer this question, Spanish Myeloma Group activated a phase III trial comparing VMP versus VTP (T for thalidomide) as induction therapy. To evaluate if the treatment regimen could be further optimized by decreasing the toxicity while maintaining efficacy, the intensity of both schedules of induction was reduced as compared with the VISTA regimen but supplemented with maintenance therapy. Between April 2005 and October 2008, 260 pts were randomized to receive 6 cycles of VMP vs VTP as induction therapy followed by maintenance with VT vs VP for up to three yrs. In the VMP arm pts received bortezomib 1.3 mg/m2 twice weekly (days 1, 4, 8, 11; 22, 25, 29 and 32) for one 6-week cycle, followed by once weekly (days 1, 8, 15 and 22) for five 5-week cycles in combination with oral melphalan 9 mg/m2 and prednisone 60 mg/m2 once daily on days 1–4 of each cycle. In the VTP arm pts received the same bortezomib and prednisone, but instead of melphalan they received thalidomide at a dose of 100 mg daily. Following the 6 cycles of induction, pts moved into maintenance that consisted in a conventional cycle of bortezomib, 1.3 mg/m2 twice weekly (days 1, 4, 8, 11) administered every three months in combination with either continuous thalidomide, 50 mg daily (VT) or prednisone, 50 mg on alternate days (VP). 253 pts are evaluable for response to induction; 125 were assigned to receive VMP and 128 to VTP. Regarding baseline characteristics, both arms were well balanced. Response rate to induction therapy was similar in both arms: ≥ PR in 81 and 79% of pts treated with VMP and VTP respectively, with a CR rate of 22% vs 27% (p=NS) and CR+nCR of 36% in both arms. Only two pts progressed under induction treatment in each arm. After a median follow-up of 22m (8-40), there weren't significant differences in terms of 2-y TTP (VMP 75% vs VTP 70%), PFS (VMP 71% vs VTP 61%) and OS (VMP 81% vs VTP 84%). 178 pts were randomized to maintenance and 143 are evaluable for efficacy. Overall, maintenance therapy was able to increase the CR rate from 25% (mean obtained after induction therapy) up to 42%, with no significant differences between VT and VP arms (46 and 38%). After a median duration of maintenance of 13 m there is a trend in favour of VT in terms of 1-y TTP (84% vs 71%; p=0.05), without differences in 1-y OS (92% for VT vs 89% for VP). 27 pts presented high-risk cytogenetic abnormalities (CA) ((4;14)t, (14;16)t, del[17p]); the CR rate was similar in this high-risk group as compared with standard risk group (26% vs 25% after induction and 42% after maintenance in both groups). There aren't differences between high-risk and standard-risk pts in the 2-y TTP (74% vs 73%) and 2-y OS (77% vs 81%) from inclusion; however, there is a trend to lower 1 y-TTP from the time to randomization to maintenance for the high-risk group compared to the standard-risk (68% vs 79%) without differences in 1 y-OS (90% vs 93%). Regarding toxicity, during the induction therapy, VMP resulted in higher incidence of ≥G3 neutropenia than VTP (37 vs 21%) and this translated into more ≥G3 infections (7 vs Disclosures: Mateos: Janssen Cilag: Honoraria, Speakers Bureau; Celgene corporation: Honoraria, Speakers Bureau. Off Label Use: VTP is not approved for the treatment of untreated MM patients. Cibeira:Jansen-Cilag: Honoraria; Celgene: Honoraria. Gutiérrez:Janssen Cilag: Honoraria; Celgene: Honoraria. García-Laraña:Janssen-Cilag: Honoraria; Celgene: Honoraria. Palomera:Janssen-Cilag: Honoraria; Celgene: Honoraria. de Arriba:Janssen-Cilag: Honoraria; Celgene: Honoraria. San-Miguel:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen–Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Several mutations and aberrant gene expression have been proposed as prognostic factors in cytogenetically normal acute myeloid leukemia (CN-AML), but few studies have analyzed the clinical value of several genes in a large group of CN-AML patients. In 121 de novo CN-AML included into the Spanish PETHEMA therapeutic protocols, we evaluated FLT3 and NPM1 mutations and BAALC , ERG , EVI1 , MLL -PTD, MN1 , PRAME , RHAMM and WT1 RNA levels. Ninety-one patients achieved CR with standard induction therapy while 20/111 (16.5%) were refractory to treatment. This latter subgroup showed higher ERG (media 1.0±0.8 vs. 0.6±0.6;p=0.012) and lower PRAME (media 28.8±52.9 vs. 1640.6±6102.0;p=0.014) levels than no-refractory patients. Moreover, high ERG expression (defined by median value) was associated with shorter OS at 2-years (38% vs. 61%;p=0.012) and RFS at 2-years (38% vs. 60%;p=0.005). By contrast, high PRAME levels (defined by 75 th percentile) was related to longer OS (61% vs. 48%;p=0.029) and RFS (74% vs. 43%;p=0.016). Additionally, high EVI expression (defined by 75 th percentile) was associated with a poorer OS (37% vs. 56%;p=0.049). The same results in OS were observed in patients with high BAALC RNA levels (median value; 41% vs. 62%; p=0.049). Interestingly, ERG , EVI1 and PRAME markers improved the current prognostic classification of CN-AML based on FLT3 and NPM1 status. Therefore, intermediate risk patients ( FLT3-ITD/NPM1mut and FLT3wt/NMP1wt ) with low ERG , low EVI1 or high PRAME achieved long OS and RFS, similar to the favorable FLT3 wt/ NPM1 mut subgroup. By contrast, the opposite expression subgroup (high ERG , high EVI1 or low PRAME ) showed OS and RFS similar to the adverse FLT3 -ITD/ NPM1 wt subset. These results allowed identify clearly two risk-subgroups for OS and RFS, based on three molecular markers ( FLT3 , NPM and one of the 3 proposed genes). In conclusion, we demonstrated that ERG , EVI1 and PRAME are relevant prognostics markers in CN-AML and they could improve their risk-stratification.