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Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell-lymphoma patient cohort from five centers in Germany and the United States (Germany, N=66; US, N=106, Total, N=172), we demonstrate that wide-spectrum antibiotics treatment (‘high-risk antibiotics’) prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely confounded by an increased pre-treatment tumor burden and systemic inflammation in high-risk antibiotics-pre-treated patients. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals impacting CAR-T efficacy, we focused on the high-risk antibiotics non-exposed patient population. Indeed, in these patients, significant correlations were uncovered between pre-CAR-T-infusion Bifidobacterium longum and microbiome-encoded peptidoglycan biosynthesis, and CAR-T treatment-associated 6-months survival or lymphoma progression. Furthermore, predictive pre-CAR-T treatment microbiome-based machine-learning algorithms trained on the high-risk antibiotics non-exposed German cohort and validated by the respective US cohort robustly segregated long-term responders from non-responders. Bacteroides, Ruminococcus, Eubacterium and Akkermansia were most important in determining CAR-T responsiveness, with Akkermansia also associating with pre-infusion peripheral T cell levels in these patients. Collectively, we uncover conserved microbiome features across clinical and geographical variations, which may enable cross-cohort microbiome-based predictions of outcomes in CAR-T cell immunotherapy.

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine( Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016- 2019) (P

This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively (

Purpose We report the long-term results of a prospective trial conducted to determine the efficacy and safety of radiation therapy (RT) alone in treating localized mucosa-associated lymphoid tissue (MALT) lymphoma. Methods and Materials Patients with localized MALT lymphoma were eligible and treated with involved field RT to doses of 24 to 39.6 Gy. Relapse-free survival (RFS) was the primary endpoint. Kaplan-Meier analysis was used to estimate RFS, progression-free survival (PFS), and overall survival (OS) defined from time of study entry. Preplanned subgroup analyses were performed based on site of involvement. Results From 2000 to 2012, 75 patients were accrued; 73 received protocol-specified RT. Median follow-up was 9.8 years. Thirty-four patients had gastric MALT, 17 orbital, 13 head and neck nonorbit, 4 skin, and 5 disease of other sites. Thirteen of 34 patients with gastric MALT were Helicobacter pylori positive at the time of initial diagnosis and underwent 1 to 3 courses of triple antibiotic therapy. All gastric MALT patients had documented persistent MALT without H. pylori on endoscopy before enrollment in the study. All patients achieved a complete response with a median time of 3 months. Eleven patients (15%) had disease relapse, 9 of which were at sites outside the RT field with median time to progression of 38.3 months. Median PFS was 17.5 years, and median RFS and OS were not reached. The 10-year relapse-free rate was 83% (95% confidence interval [CI], 74%-93%). The 10-year PFS rate was 71% (95% CI, 60%-84%). The 10-year OS rate was 86% (95% CI, 77%-96%). RFS, PFS, and OS did not differ by disease site (P = .17, .43, and .50, respectively). All relapses were successfully salvaged. One patient developed metastatic gastric adenocarcinoma and was found to also have recurrent MALT on biopsy. Otherwise, all relapsed patients were alive without evidence of disease at last follow-up, and no patient died of MALT lymphoma. Sixty-seven patients (92%) experienced acute toxicity during radiation, all of which were grade 1 and 2, with only 1 grade 3 toxicity. Twenty-two patients (30%) experienced late toxicity, with only 1 grade 3 toxicity. Conclusions This prospective study confirms that RT for MALT lymphoma provides excellent long-term RFS with acceptable rates of toxicity. Current efforts are focused on RT de-escalation in an effort to further avoid treatment-related morbidity. Clinicaltrials.gov NCT04465162 .

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity, with limited data on the outcome in the relapsed/refractory setting. We evaluated the outcome of all patients diagnosed between 04/1979 and 01/2019 with relapsed or progressive NLPHL after initial active therapy at two institutions, refractory disease being defined as lack of response to treatment and/or relapse within three months of treatment. NLPHL patients with histological evidence of transformation at time of first relapse or progression were excluded. In total, 69 patients with recurrent NLPHL were included in the study. After a median follow-up after initial diagnosis of 14 years (range, 0·5-46 years), median progression-free survival after front-line treatment (PFS-1) was four years. Second-line therapy included chemotherapy in 28 (41%) patients, biological therapy (rituximab, lenalidomide or brentuximab vedotin) in 14 (20%), high-dose chemotherapy followed by autologous stem cell transplant in 14 (20%) and radiation therapy (RT) alone in 10 (15%). The five-year PFS after second-line therapy (PFS-2) was 68% [95% confidence interval (CI), 54-79%] but the five-year overall survival (OS) after second-line therapy (OS-2) remained excellent, at 94% (95% CI, 85-99%). Due to excellent outcome in case of recurrence, studies aimed at characterizing its biology to guide therapy de-escalation are needed.

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (D...

Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P = .03) and C-reactive protein (P = .001) levels and a low peak monocyte count (P = .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P = .02) and overall survival (progression being the most common cause of death; P = .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.

Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin Lymphoma (NHL) that can be further classified into 3 sub-types: nodal, extra-nodal and splenic [1]. MZL rarely involves the central ne...

Conditioning chemotherapy (CCT) has been shown to be essential for optimal efficacy of chimeric antigen receptor (CAR) T-cell therapy. Here, we determined whether the change in absolute lymphocyte count, referred to as delta lymphocyte index (DLIx), may serve as a surrogate marker for pharmacodynamic effects of CCT and whether it associated with germline genetic variants in patients with large B-cell lymphoma (LBCL). One-hundred and seventy-one patients were included, of which 86 (50%) received bridging therapy post-leukapheresis. Median DLIx was 0.5 × 10(9)/L (range, 0.01–2.75 X 10(9)/L) and was significantly higher in patients who achieved complete response (p=0.04). On multivariate analysis, low DLIx was associated only with use of bridging therapy (odds ratio 0.4, 95% CI 0.2–0.8, p=0.007). Low DLIx was independently associated with shorter progression-free (p=0.02) and overall survival (p=0.02). DLIx was associated with genetic variations related to drug metabolism and macrophage biology such as ABCB1, MISP and CPVL. The impact of CCT on lymphocyte count is affected by use of bridging therapy but change in lymphocyte count is independently associated with efficacy. Studies aimed at investigating macrophage biology in this setting may suggest strategies to increase the efficacy of CCT and improve outcomes.

About 70% of patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel) and who achieve a partial response (PR) or stable disease (SD) on the day 30 (D30) positron emission tomography (PET)–computed tomography (CT) scan progress; however, the factors that are predictive of progression are unknown. This a retrospective study of patients with LBCL who were treated with axi-cel at MD Anderson Cancer Center between January of 2018 and February of 2021. Among 50 patients with D30 PR/SD, 13 (26%) converted to a complete response (CR). Among 95 patients with a D30 CR, 72 (76%) remained in CR. On univariate analysis, the only day −5 characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (P = .05). The only D30 factor associated with conversion from D30 PR/SD to subsequent CR was a lower maximum standardized uptake volume (SUVmax; P < .001); all patients with D30 SUVmax ≥ 10 progressed. After a median follow-up of 12 months, no significant difference in median progression-free survival was observed between patients who converted from D30 PR/SD to subsequent CR and those who had been in CR since D30 (P = .19). Novel predictive and prognostic markers based on tissue biopsy and noninvasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease.

In 2 randomized phase 3 trials BR resulted in longer progression-free survival (PFS) than frontline R-CHOP in patients with indolent and mantle cell lymphoma. However, in subset analyses of follicu...

Many patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will not respond to platinum-containing salvage chemotherapy. Predicting treatment failure earlier could help clinicians minimize chemotherapy toxicities for non-responders in favor of other treatments. We conducted a pilot study where 2 early PET/CTs were obtained on days 4 (D4) and 21 (D21) of cycle 1 (C1) of salvage therapy for DLBCL. Twenty-five patients were enrolled and have evaluable data. Ten (40%) had an unplanned therapy change after C1 and before end-of-treatment (EOT) evaluation due to treatment failure on early PET/CT as interpreted by the treating physician. Early PET/CT response at D4 or D21 was not associated with EOT response in evaluable patients. Disease specific survival was longer for patients with a persistent response on both D4 and D21 (p = 0.042). Early PET/CT may predict salvage chemotherapy failure and could inform future clinical trials investigating early therapy change to non-chemotherapy treatments.

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 – 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively. There were no differences in OS, PFS, or LRFS based on COO or MYC/Bcl-2 dual expression (DE). Similarly, patients with MYC translocations without BCL2 or BCL6 rearrangements did not have worse outcomes. Consolidative RT produced excellent local control, regardless of DLBCL biology, with one late in-field failure.

Corticosteroids are used to treat the acute complications of chimeric antigen receptor (CAR) T-cell therapy. Strati et al examine the impact of corticosteroids on patient outcomes following CAR T-cell therapy for large B-cell lymphoma. Use of higher doses of steroids is associated with shorter progression-free survival at 10 months and decreased overall survival., Key Points Higher cumulative dose of corticosteroids is associated with early progression after CAR-T therapy in large B-cell lymphoma.Higher cumulative dose and prolonged, early corticosteroid use is associated with shorter overall survival after CAR-T therapy., Visual Abstract, Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy–associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy–associated toxicities.

Key Points Question What are the radiation doses to normal tissues for patients with favorable Hodgkin lymphoma treated with modern involved-site radiation therapy? Findings This case series study included 42 patients with early-stage favorable Hodgkin lymphoma who were treated with combined modality therapy. The mean heart dose was less than 5 Gy in all patients, and the mean breast dose was 1 Gy or less in all 18 women. Meaning In this study, combined modality therapy for favorable Hodgkin lymphoma with contemporary radiation therapy delivered low radiation doses to organs at risk., This case series study investigates the radiation doses delivered to organs at risk with modern involved-site radiation therapy among patients with early-stage favorable Hodgkin lymphoma treated with 20 Gy after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)., Importance Response-adapted randomized trials have used positron emission tomography–computed tomography to attempt to identify patients with early-stage favorable Hodgkin lymphoma (ESFHL) who could be treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiation therapy (RT). While maximal efficacy is demonstrated with combined modality therapy, RT is often omitted in fear of late adverse effects; however, the application of modern RT could limit these toxic effects. Objective To determine the radiation doses delivered to organs at risk with modern involved-site RT among patients with ESFHL treated with 20 Gy after 2 cycles of ABVD. Design, Setting, and Participants This case series included 42 adult patients with ESFHL (according to the German Hodgkin Study Group criteria) who were treated between 2010 and 2019, achieved complete response by positron emission tomography–computed tomography (1-3 on 5-point scale) following 2 cycles of ABVD, and then received consolidative RT. The study was conducted at a single comprehensive cancer center. Exposures 2 cycles of chemotherapy followed by 20-Gy involved-site RT. Main Outcomes and Measures The medical records of patients with ESFHL were examined. Organs at risk were contoured, and doses were calculated. Progression-free survival, defined from date of diagnosis to disease progression, relapse, or death, and overall survival were estimated using the Kaplan-Meier method. Results The cohort comprised 42 patients with ESFHL (median [range] age at diagnosis, 35 [18-74] years; 18 [43%] women; 24 [57%] with stage II disease). At a median follow-up of 44.6 (95% CI, 27.6-61.6) months, the 3-year progression-free survival and overall survival rates were 91.2% (95% CI, 74.9%-97.1%) and 97.0% (95% CI, 80.4%-99.6%), respectively. The mean heart dose was less than 5 Gy (mean, 0.8 Gy; SD, 1.5 Gy; range, 0-4.8 Gy) in all patients. The mean (SD) breast dose for both breasts was 0.1 (0.2) Gy (left breast range, 0-1.0 Gy; right breast range, 0-0.9 Gy). Conclusions and Relevance In this study, combined modality therapy with 2 cycles of ABVD and 20 Gy for ESFHL was highly effective and avoided excess doses to organs at risk, which may limit long-term toxic effects.

In recent years, cancer treatment has evolved, and new therapies have been introduced with significant improvement in prognosis. The immunotherapies stand out owing to their efficacy and remission rate. Chimeric antigen receptor (CAR) T-cell therapy is a part of this new era of therapies. Chimeric antigen receptor T-cell therapy is a form of adoptive cellular therapy that uses a genetically encoded CAR in modified human T cells to target specific tumor antigens in a nonconventional, non-major histocompatibility complex (MHC) protein presentation. Chimeric antigen receptor T-cell therapy successfully identifies tumor antigens and through activation of T cells destroys tumoral cells. It has been found to efficiently induce remission in patients who have been previously treated for B-cell malignancies and have persistent disease. As the use of this novel therapy increases, its potential side effects also have become more evident, including major complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokine release syndrome is a major systemic inflammatory process as a result of massive cytokine production by the proliferating and activated CAR T cells in which multiple interleukins and immune cells contribute to the inflammatory response. Cytokine release syndrome has been associated with cardiovascular life-threatening complications including hypotension, shock, tachycardia, arrhythmias, left ventricular dysfunction, heart failure, and cardiovascular death. Arrhythmias, among its major complications, vary from asymptomatic prolonged corrected QT interval (QTc) to supraventricular tachycardia, atrial fibrillation, flutter, and ventricular arrhythmias like Torsade de pointes. This article focuses on the cardiovascular complications and arrhythmias associated with CRS and CAR T-cell therapy.

The impact of bridging therapy (BT) administered between leukapheresis and chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is unclear. We evaluated the influence of BT (systemic therapy [ST], radiation therapy [RT], or combined-modality therapy [CMT]) on outcomes of 148 LBCL patients who underwent leukapheresis for planned axicabtagene ciloleucel (axi-cel) infusion. The 55% (n = 81) of patients who received BT were more likely to have international prognostic index (IPI) score ≥3 (P ≤ .01), bulky disease (P = .01), and elevated lactate dehydrogenase (LDH; P ≤ .01). The 1-year progression-free (PFS) and overall survival (OS) rates were 40% and 65% in non-BT patients vs 21% and 48% in BT patients (P = .01 and .05, respectively). Twenty-four patients (16%) did not receive axi-cel, most commonly because of lymphoma progression (88%), despite 80% (n = 19) receiving BT. Among 124 patients who received axi-cel, 50% (n = 62) received BT with ST (n = 45), RT (n = 11), or CMT (n = 6); 1-year PFS and OS rates were not significantly different between BT and non-BT cohorts (P = .06 and .21, respectively). There was no difference in proportion of patients with IPI ≥3, limited-stage disease, or elevated LDH between ST, RT, and CMT groups. Compared with non-BT patients, 1-year PFS was inferior for ST-bridged patients (P = .01). RT-bridged patients had improved PFS compared with ST-bridged patients (P = .05). Despite the poor prognosis associated with requiring BT, RT can be an effective bridging strategy. Future studies are necessary to identify strategies that may improve access to CAR T-cell therapy and outcomes.

Multiple myeloma (MM) and Waldenström's macroglobulinemia (WM) are plasma cell disorders often treated with proteasome inhibitors. Recently, several studies evaluated carfilzomib as an initial treatment for these diseases and reported outstanding clinical outcomes. We conducted a retrospective study to report the efficacy and safety of frontline carfilzomib-based combinations in a standard of care setting. From 2014 until 2016 we identified newly diagnosed MM (n = 54) and WM (n = 6) patients treated with carfilzomib as initial therapy who met study inclusion criteria. The response rate for myeloma patients was 98% with 77% of patients undergoing upfront autologous stem cell transplant. The clinical benefit for WM was 100% with all patients having a resolution of B symptoms and anemia after treatment. Carfilzomib-based regimens are well tolerated and offer a neuropathy sparing approach with excellent responses both in newly diagnosed MM and WM making them a good choice for the frontline treatment of these diseases.

Background: About one third of patients with relapsed or refractory (r/r) large B-cell lymphoma (LBCL) treated with autologous anti-CD19 CAR T-cell therapy achieve a partial response (PR) or a stable disease (SD) on day 30 (D30) PET-CT scan. Among these patients, only 30% will convert later to a complete response (CR), while 70% will eventually progress, experiencing significantly poor outcomes. Therefore, early identification of patients with D30 PR at risk for subsequent progression is of utmost importance and could allow for the development of novel consolidation strategies. Methods: This is a retrospective study of all patients with r/r LBCL treated with standard of care axicabtagene ciloleucel (axi-cel) at MD Anderson Cancer Center between 01/2018 and 02/2021 (data cut-off 04/2021). Clinical, laboratory and radiological characteristics were collected on day -5 and D30. All patients received lymphodepleting chemotherapy with cyclophosphamide and fludarabine. CRS and ICANS were prospectively graded according to CARTOX criteria from 01/2018 to 04/2019, and ASTCT criteria from 05/2019 onward. Response to treatment and progression were defined according to 2014 Lugano criteria. The association with categorical variables was evaluated using χ2 or Fisher exact tests, as appropriate. The difference in a continuous variable between patient groups was evaluated by the Mann-Whitney test. Results: By D30, 204 out of 206 patients were evaluable for response (2 were lost to follow-up). Among 204 evaluable patients, 102 (50%) achieved CR, 49 (24%) PR, 8 (4%) SD, and 45 (22%) progressive disease (PD)/death. Among the 57 patients who achieved PR/SD on the D30 PET-CT scan, 50 were evaluable for response at day 90 or beyond, and were included in the analysis, 5 were lost to follow-up, and 2 died of unrelated cause before restaging. Among the 50 patients with D30 PR/SD, 13 (26%) converted to CR on subsequent restaging, and 37 (74%) progressed and/or died of progressive disease. Among the 102 patients with D30 CR, 7 were lost to follow-up. In the remaining 95 evaluable patients, 72 (76%) remained in CR at day 90 restaging, and 13 (24%) progressed/died (Figure A). On univariate analysis, among baseline characteristics (day -5), including age, sex, performance status, international prognostic index score, laboratory values, SUV max, number of previous therapies, prior stem cell transplant, and use of bridging therapy, the only characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (median, 193 vs 128 X10 9/L, p=0.05); a trend for association with lower c-reactive protein was also observed (13.7 vs 36 mg/L, p=0.06). No difference in baseline characteristics was observed when comparing patients in CR since D30 to those with D30 PR who subsequently converted to CR. D30 laboratory, clinical and radiological characteristics were evaluated, and the only factor associated with conversion from D30 PR to subsequent CR was lower D30 SUV max (median 5.8 vs 9.8, p= 10 eventually progressing (Figure B). After a median follow-up of 12 months (95%CI, 11-13 months), no significant difference in median PFS was observed when comparing the 13 patients who converted from D30 PR/SD to subsequent CR to the 72 patients who had been in CR since D30 (1-year PFS rate, 100% vs 84%, p=0.19)(Figure C). No significant difference in median PFS was observed also in a landmark analysis at 90 days (p=0.19). Conclusions: Patients with D30 PR/SD subsequently converting to CR experience similar early outcomes as patients who achieved CR by D30. PET-associated parameters, such as SUV max of 10 or higher, may help identify patients with D30 PR/SD at risk of subsequent progression, who may benefit from clinical trials of consolidation therapy. Novel predictive and prognostic markers based on tissue biopsy for patients with D30 PR/SD and non-invasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease. Figure 1 Figure 1. Disclosures Westin: Umoja: Consultancy; ADC Therapeutics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Curis: Research Funding; Iksuda Therapeutics: Consultancy; Genentech: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; 47 Inc: Research Funding; Morphosys: Research Funding. Ahmed: Xencor: Research Funding; Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding. Nastoupil: Denovo Pharma: Other: DSMC; Gilead/Kite: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Novartis: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Pfizer: Honoraria, Research Funding; Bayer: Honoraria; Genentech: Honoraria, Research Funding; IGM Biosciences: Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Epizyme: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; MorphoSys: Honoraria. Steiner: Seattle Genetics: Research Funding; BMS: Research Funding; Rafael Pharmaceuticals: Research Funding. Flowers: Epizyme, Inc.: Consultancy; Acerta: Research Funding; Celgene: Consultancy, Research Funding; Denovo: Consultancy; Guardant: Research Funding; Cellectis: Research Funding; Pharmacyclics/Janssen: Consultancy; Iovance: Research Funding; Ziopharm: Research Funding; AbbVie: Consultancy, Research Funding; 4D: Research Funding; Biopharma: Consultancy; Janssen: Research Funding; Allogene: Research Funding; Novartis: Research Funding; Burroughs Wellcome Fund: Research Funding; Karyopharm: Consultancy; Genentech/Roche: Consultancy, Research Funding; Takeda: Research Funding; Nektar: Research Funding; Sanofi: Research Funding; Xencor: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Pfizer: Research Funding; Kite: Research Funding; TG Therapeutics: Research Funding; BeiGene: Consultancy; Bayer: Consultancy, Research Funding; EMD: Research Funding; Morphosys: Research Funding; Adaptimmune: Research Funding; Amgen: Research Funding; Genmab: Consultancy; SeaGen: Consultancy; Gilead: Consultancy, Research Funding; Spectrum: Consultancy; National Cancer Institute: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Pharmacyclics: Research Funding. Shpall: Novartis: Honoraria; Magenta: Honoraria; Magenta: Consultancy; Adaptimmune: Consultancy; Takeda: Patents & Royalties; Novartis: Consultancy; Affimed: Patents & Royalties; Navan: Consultancy; Axio: Consultancy; Bayer HealthCare Pharmaceuticals: Honoraria. Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees. Strati: Roche-Genentech: Consultancy; Astrazeneca-Acerta: Research Funding.

Introduction: Plasmablastic lymphoma (PBL) is a rare subtype of non-Hodgkin B-cell lymphoma (NHL), often characterized by immunoblastic morphology and plasmacytic immunophenotype. PBL was initially described in HIV-positive patients (pts) and is now often diagnosed in post-transplant and HIV-negative pts with other immunodeficiency. Pts with limited stage disease treated with induction chemotherapy and consolidative radiotherapy have a good prognosis; however, pts with advanced stage have poor outcome. Previously studied treatment regimens vary and include CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone), HyperCVAD (cyclophosphamide, vincristine, Adriamycin, dexamethasone alternating with methotrexate and cytarabine), and DA-EPOCH (etoposide, vincristine, cyclophosphamide, Adriamycin, prednisone) with or without radiation and autologous stem cell transplant, with no current standard therapy, largely due to the rarity of PBL. Methods: We conducted a retrospective analysis of pts diagnosed with PBL between April 2003 and August 2020 to describe outcomes for pts treated at our center over the past 2 decades. We hope to use this to improve outcomes with novel therapies in the future. We evaluated the baseline demographics, stage, therapy, response rate, progression-free survival (PFS) and overall survival (OS). We used descriptive statistics including mean, standard deviation, median, and range for continuous variables, and frequency counts and percentages for categorical variables. Best response and its 95% exact confidence interval were calculated. Kaplan-Meier method was used to estimate the time-to-event endpoints including progression free survival, and overall survival. Results: 39 pts with PBL were identified, with a median age of 51 years (range 27-91). 16 were HIV+, and 5 were on immunosuppression for autoimmune disease (2), infectious hepatitis (2), or liver transplant (1); the other 18 had no apparent immunosuppression other than advanced age (defined as 70 years and older) in 13. Among those with HIV, 14 were on antiretroviral therapy at time of diagnosis of PBL. The median CD4 count was 140 (range 15-391) and 5 patients had an active viral load. 24 pts were EBV/EBER positive. 6 pts had stage III disease and 33 had stage IV disease. The primary sites of disease included head and neck (13), lymph node (7), gastrointestinal tract (6), other soft tissue (3), abdomen (3), breast (2), gynecologic (2), skin (2), and bone (1). The median LDH was 629 IU/L (313-618). A serum protein electrophoresis was checked in 21 pts and the median was 1.4 g/dL (range 0.2-2.6 g/dL, normal = 0). A beta 2 microglobulin was checked in 28 pts and the median was 3.95 (range 2.55-10.4, normal =0.8 to 2.3 mg/L). The median Ki-67 proliferation index was 85%, and the PBL cells were invariably CD20 negative. 12 cases showed MYC overexpression; 2 had MYC rearrangement by FISH. 32 pts received systemic therapy and were evaluable with 2 median lines of treatment (range 1-6). First line therapy included Hyper-CVAD (n=7), CHOP (n=3), EPOCH (n=19), and other (n=3). The antimyeloma therapy, bortezomib, a proteasome inhibitor, was added to EPOCH for 4 patients or used with dexamethasone in one pt, while the CD38 antibody daratumumab was added to hypercytoxan for the first cycle of an elderly pt with poor performance status (PS). He responded well with improvement in his PS, and subsequently completed 5 cycles of DA-EPOCH and remains in CR. After first line therapy, 59% pts achieved complete response, 13% partial response, and 9% stable disease. 20 pts received intrathecal chemotherapy, 9 pts received radiation, and 8 pts underwent autologous stem cell transplantation (7 as consolidation and 1 at relapse). Please see figure for PFS and OS based on different treatment modalities. Median PFS and OS were 21 and 35.2 months, respectively. Median follow up time was 25.85 months. Conclusions: The majority of our pts (87%) with advanced stage PBL were immunocompromised with HIV (16), requiring immunosuppression (5), or elderly (13). Despite a 56% CR rate with induction, 69% of patients relapsed. Median PFS was less than 2 years and OS was less than 3 years. The dismal outcomes of pts with PBL suggests that this rare and aggressive subtype of NHL with plasmacytic differentiation requires further evaluation with therapies against plasma cell directed antigens such as CD38, BCMA or SLAMF7. *S Lee & C Dillard contributed equally. Figure 1 Figure 1. Disclosures Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Loghavi: Abbvie: Current equity holder in publicly-traded company; Curio Sciences: Honoraria; Gerson Lehrman Group: Consultancy; Guidepoint: Consultancy; Peerview: Honoraria; Qualworld: Consultancy. Ahmed: Seagen: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Xencor: Research Funding. Patel: Pfizer: Consultancy; Janssen: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Oncopeptides: Consultancy.

INTRODUCTION: Anaplastic large cell lymphoma, ALK-positive (ALK+ ALCL), is an aggressive CD30 positive T-cell lymphoma. The use of brentuximab vedotin (BV) in the frontline setting has demonstrated improved outcomes. However, data outside of controlled settings such as clinical trials are lacking. Although the overall prognosis of ALK+ ALCL is remarkably better than other T-cell lymphomas, no particular risk factors predictive of early relapse and mortality have been clearly identified. Therefore, we conducted a retrospective review of newly diagnosed ALK+ ALCL managed with systemic therapy and to identify clinico-pathologic characteristics associated with early relapse and mortality. METHODS: We retrospectively analyzed patients with untreated ALK+ ALCL diagnosed between 2002 and 2020 at The University of Texas MD Anderson Cancer Center. The study outcomes were overall survival (OS) and progression-free survival (PFS). The International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (PIT) scores were used for risk stratification. The therapy approaches used during the patients' disease process were divided as follow: BV-based therapy (either alone or in combination with chemotherapy); and non-BV-based therapy. Kaplan-Meier and log-rank test were used for survival analysis. Univariate and multivariate Cox regression analysis were used to estimate hazard ratios (HR) with a 95% confidence interval (CI). Outcomes with a p-value RESULTS: We identified 117 patients, 11 were excluded due to incomplete data. In the remaining 106 patients, the median age at diagnosis was 39 years (range 23-81, 83% CONCLUSION: This large cohort of ALK+ ALCL patients was characterized by younger age, good performance status, advanced disease, and low- to intermediate-risk IPI/PIT scores. Although CR rates to first-line therapy were over 85% with both BV- and non-BV-based regimens, only frontline BV-based regimens conferred improved PFS. Furthermore, bone marrow involvement was associated to shorter OS and PFS. Response rates after salvage therapy were high, but with shorter PFS. In conclusion, this study suggest the addition of BV as the preferred regimen in the management of ALK+ ALCL; a more aggressive approach might be considered to those deemed as high risk for early mortality and relapse (i.e., bone marrow involvement). Further analysis with pathologic and molecular studies are ongoing and results will be reported at the meeting. Figure 1 Figure 1. Disclosures Jain: Lilly: Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy. Chihara: Astrazeneca: Honoraria. Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Samaniego: Arog: Research Funding; Imbrium: Membership on an entity's Board of Directors or advisory committees. Ahmed: Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding; Xencor: Research Funding; Merck: Research Funding. 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. Nastoupil: Takeda: Honoraria, Other: DSMC, Research Funding; Caribou Biosciences: Research Funding; Janssen: Honoraria, Research Funding; Gilead/Kite: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; MorphoSys: Honoraria; TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bayer: Honoraria; Epizyme: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; IGM Biosciences: Research Funding; Denovo Pharma: Other: DSMC. Hosing: Nkarta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Vega: CRISPR Therapeutics and Geron: Research Funding; i3Health, Elsevier, America Registry of Pathology, Congressionally Directed Medical Research Program, and the Society of Hematology Oncology: Research Funding. Pinnix: Merck Inc: Research Funding. Wang: OMI: Honoraria; VelosBio: Consultancy, Research Funding; The First Afflicted Hospital of Zhejiang University: Honoraria; CAHON: Honoraria; BioInvent: Research Funding; Dava Oncology: Honoraria; CStone: Consultancy; Kite Pharma: Consultancy, Honoraria, Research Funding; InnoCare: Consultancy, Research Funding; Imedex: Honoraria; Lilly: Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Moffit Cancer Center: Honoraria; Epizyme: Consultancy, Honoraria; Hebei Cancer Prevention Federation: Honoraria; Clinical Care Options: Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Newbridge Pharmaceuticals: Honoraria; Genentech: Consultancy; Chinese Medical Association: Honoraria; Molecular Templates: Research Funding; DTRM Biopharma (Cayman) Limited: Consultancy; BGICS: Honoraria; Celgene: Research Funding; Bayer Healthcare: Consultancy; Mumbai Hematology Group: Honoraria; Physicians Education Resources (PER): Honoraria; Scripps: Honoraria; Pharmacyclics: Consultancy, Research Funding; Juno: Consultancy, Research Funding; Oncternal: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Loxo Oncology: Consultancy, Research Funding; Anticancer Association: Honoraria; Acerta Pharma: Consultancy, Honoraria, Research Funding. Neelapu: Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria. Flowers: Kite: Research Funding; BeiGene: Consultancy; EMD: Research Funding; Janssen: Research Funding; AbbVie: Consultancy, Research Funding; Xencor: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Celgene: Consultancy, Research Funding; Denovo: Consultancy; TG Therapeutics: Research Funding; Biopharma: Consultancy; Takeda: Research Funding; Ziopharm: Research Funding; Sanofi: Research Funding; Genentech/Roche: Consultancy, Research Funding; Genmab: Consultancy; Gilead: Consultancy, Research Funding; Epizyme, Inc.: Consultancy; National Cancer Institute: Research Funding; Karyopharm: Consultancy; Pharmacyclics/Janssen: Consultancy; SeaGen: Consultancy; Bayer: Consultancy, Research Funding; Guardant: Research Funding; Spectrum: Consultancy; Morphosys: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; 4D: Research Funding; Iovance: Research Funding; Nektar: Research Funding; Cellectis: Research Funding; Acerta: Research Funding; Amgen: Research Funding; Allogene: Research Funding; Adaptimmune: Research Funding; Pharmacyclics: Research Funding. Iyer: CRISPRX: Research Funding; Seattle Genetics: Research Funding; Rhizen: Research Funding; Merck: Research Funding; Legend: Research Funding; Innate: Research Funding; Spectrum: Research Funding; Trillium: Research Funding; Astra Zeneca: Research Funding; Yingli: Research Funding; Cyclacel: Research Funding.

Background: Hodgkin's lymphoma (HL) is a curable malignancy. However, some patients are refractory to frontline therapy. Early prediction of response to frontline therapy could identify patients who may benefit from more intensive therapy. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has an established role in the management of HL. Radiomic features provide a way of quantifying imaging phenotypes and have shown promising results as predictors of outcomes in different lymphomas. Furthermore, great interest has been focused on the heterogeneity of standardized uptake value (SUV) within a single lesion. Since high SUV component (HSc) and low-SUV component (LSc) regions within a single lesion may be associated with different phenotypical characteristics, the radiomic analysis for each regional SUV component may provide a more complete description of lesions. Therefore, we proposed and evaluated new descriptors to quantify the image phenotypes based on HSc and LSc of lesions in HL. Methods: A total of 61 patients with HL of all stages who were seen at MD Anderson Cancer Center between 2016 and 2020 and had analyzable pre-treatment PET/CT were selected. All patients received standard of care ABVD or AVD regimens with or without radiation (Table 1A). Pre-treatment PET/CT scans were analyzed, and HL lesions were semi-automatically segmented using MIM 7 (Cleveland, OH) based on a SUV max threshold of 2.5. Manual edits were made and reviewed by a nuclear medicine physician and a lymphoma specialist. A total of 110 radiomic features were extracted from the segmented lesions in CT and PET using the open-source package of 'PyRadiomics' (Table 1B). Detailed description and algorithms of the extracted radiomics features are available at https://pyradiomics.readthedocs.io/en/latest/features.html. Additionally, each lesion was partitioned into HSc and LSc based on a cutoff value of 3 times the liver SUV mean (Figure A). The ratio of features between SUV components (HSc, LSc) and the lesion area was calculated. Furthermore, the feature difference between HSc and LSc was obtained. The maximum, minimum, average, and standard deviation of the radiomic features within multiple lesions were computed to reveal the distribution of features. A sequential forward feature selection was applied to select the significant features for building a logistic regression model, to predict refractory disease according to Lugano criteria. Two logistic regression models were constructed for early and advanced stage patients. Quantitative measures, namely metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUV max were measured for comparison. The leave-one-out-cross-validation (LOOCV) was applied to yield the receiver-operator-characteristics curve; the area under the curve (AUC) was then computed to evaluate the performance of the proposed model compared to quantitative measurements using DeLong's test. Results: The average of small dependence high gray level emphasis (GLDM) from PET, the difference of major axis length between high- and low- SUV component from PET, and the difference of 10th Percentile (histogram) between high- and low- SUV component from PET were selected for identifying the refractory disease in early stage lesions; the maximum of correlation (GLCM) from PET, SD of small dependence emphasis (GLDM) from PET, and SD of the inverse difference moment normalized (GLCM) from PET were selected for identifying refractory disease in advanced stage lesions. Based on LOOCV, the proposed radiomics model achieved an AUC of 0.93 for refractory disease prediction, which was significantly superior to MTV (AUC, 0.66; P = 0.01), TLG (AUC, 0.64; P = 0.01), and SUV max (AUC, 0.61; P = 0.01) (Figure B) Conclusion: High and low SUV components-based radiomic model of PET/CT was potentially useful for upfront prediction of refractory HL. Validation in a larger cohort using different segmentation methods, inclusion of additional treatment subgroups, comparison to other predictors, and correlation with survival outcomes are underway. Figure 1 Figure 1. Disclosures Ahmed: Seagen: Research Funding; Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Xencor: Research Funding. Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Pinnix: Merck Inc: Research Funding. Wang: Molecular Templates: Research Funding; The First Afflicted Hospital of Zhejiang University: Honoraria; Hebei Cancer Prevention Federation: Honoraria; Bayer Healthcare: Consultancy; Mumbai Hematology Group: Honoraria; Pharmacyclics: Consultancy, Research Funding; BioInvent: Research Funding; Celgene: Research Funding; Physicians Education Resources (PER): Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Scripps: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Imedex: Honoraria; Dava Oncology: Honoraria; Epizyme: Consultancy, Honoraria; Clinical Care Options: Honoraria; BGICS: Honoraria; CAHON: Honoraria; VelosBio: Consultancy, Research Funding; Loxo Oncology: Consultancy, Research Funding; InnoCare: Consultancy, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Anticancer Association: Honoraria; Genentech: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; CStone: Consultancy; Newbridge Pharmaceuticals: Honoraria; Juno: Consultancy, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Chinese Medical Association: Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Oncternal: Consultancy, Research Funding; DTRM Biopharma (Cayman) Limited: Consultancy; OMI: Honoraria; Moffit Cancer Center: Honoraria; Lilly: Research Funding.

Introduction. Suboptimal CAR T-cell stimulation, expansion, and persistence is of theoretical concern in absence of CD19+ tumor B-cells. Adequate CAR T-cell expansion has been reported in the JULIET study among 7 relapsed or refractory (r/r) large B-cell lymphoma (LBCL) patients who had achieved complete metabolic remission (CMR) before tisagenlecleucel (tisa-cel) infusion. As patients in CMR at time of infusion were excluded from the ZUMA-1 trial, the efficacy of axicabtagene ciloleucel (axi-cel), whose construct and kinetics differ significantly from those of tisa-cel, remains unknown in this population. Methods. This is a retrospective study of all patients with r/r LBCL treated with standard of care (SOC) axi-cel at MD Anderson Cancer Center between 01/2018 and 02/2021 (data cut-off 04/2021). CMR was defined as a Deauville score Results. Two-hundred and six patients with R/R LBCL received SOC axi-cel between 01/2018 and 02/2021. Of these, 162 had a PET-CT scan performed after bridging therapy and before LDC, 10 of whom were in CMR at time of axi-cel infusion. The immediate treatment before achievement of CMR consisted of chemoimmunotherapy in 5 patients (platinum-based in 4 patients, methotrexate-based in 1 patient), radiation therapy in 3 patients, and biological therapy in 2 patients (lenalidomide and rituximab in 1 patient, and ibrutinib in 1 patient). When comparing the 152 patients with metabolically active disease to the 10 patients without, patients with active disease had more frequently at baseline (day -5) an international prognostic index score >= 3 (58% vs 10%, p=0.006), elevated lactate dehydrogenase (LDH)(70% vs 10%, p Interestingly, when comparing patients with active disease to those without, no difference for CRS of any grade (94% vs 90%, p=0.48), grade 3-4 CRS (8% vs 10%, p=0.58), ICANS of any grade (61% vs 70%, p=0.74) or grade 3-4 ICANS (38% vs 40%, p=1) was observed (Figure A). After a median follow-up of 12 months (95% CI, 11-13 months), 87 (54%) patients progressed and/or died, and median progression-free survival (PFS) was 6 months (95% CI, 2-10 months). Median PFS was significantly longer for patients without metabolically active disease at the time of axi-cel infusion (not reached vs 5 months, p=0.04) with a 1-year PFS rate of 80% as compared to 45% (Figure B). At most recent follow-up, 57 (35%) patients died, and median overall (OS) was not reached. One-year OS rate was higher for patients without metabolically active disease at baseline (80% vs 64%), but not statistically significant (p=0.23)(Figure C). Conclusions. Our data support the use of axi-cel in r/r LBCL patients who achieve a CMR before axi-cel infusion, warranting further investigation of its activity as consolidative strategy in future trials. Identification of effective and biologically rational bridging therapies aimed at decreasing disease burden and continue to improve outcomes in patients treated with axi-cel is needed. CAR T-cell amplification data by qPCR and pre-infusion levels of CD19+ non-tumoral B-cells in peripheral blood are being analyzed and will be presented at the conference. Figure 1 Figure 1. Disclosures Westin: Genentech: Consultancy, Research Funding; Iksuda Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Umoja: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Curis: Research Funding; Morphosys: Research Funding; 47 Inc: Research Funding. Steiner: Rafael Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; BMS: Research Funding. Parmar: Cellenkos Inc.: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Fowler: BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company; 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. Flowers: Denovo: Consultancy; Burroughs Wellcome Fund: Research Funding; AbbVie: Consultancy, Research Funding; Acerta: Research Funding; Kite: Research Funding; Karyopharm: Consultancy; EMD: Research Funding; BeiGene: Consultancy; Takeda: Research Funding; Sanofi: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Genmab: Consultancy; Iovance: Research Funding; Allogene: Research Funding; TG Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; National Cancer Institute: Research Funding; Amgen: Research Funding; Cellectis: Research Funding; Nektar: Research Funding; Xencor: Research Funding; Spectrum: Consultancy; Ziopharm: Research Funding; Genentech/Roche: Consultancy, Research Funding; Pharmacyclics/Janssen: Consultancy; Bayer: Consultancy, Research Funding; Morphosys: Research Funding; Biopharma: Consultancy; SeaGen: Consultancy; 4D: Research Funding; Janssen: Research Funding; Gilead: Consultancy, Research Funding; Epizyme, Inc.: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Guardant: Research Funding; Adaptimmune: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding. Ahmed: Xencor: Research Funding; Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding. Nastoupil: Genentech: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; Gilead/Kite: Honoraria, Research Funding; IGM Biosciences: Research Funding; Denovo Pharma: Other: DSMC; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Epizyme: Honoraria, Research Funding; MorphoSys: Honoraria; Caribou Biosciences: Research Funding; ADC Therapeutics: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bayer: Honoraria. Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees. Strati: Roche-Genentech: Consultancy; Astrazeneca-Acerta: Research Funding.