ALBERT

Description: Abstract 3131 Introduction: Although MCL is reported to be an FDG-avid NHL subtype, PET-CT is not currently recommended in the modified IWG criteria (Chesen et al, JCO 2007) to stage, survey and assess treatment response in MCL. PET-CT is however frequently used for these purposes in clinical practice in MCL. Although convincing data exists regarding the prognostic utility of PET-CT imaging in Hodgkin Lymphoma (interim & post treatment) and DLBCL (post treatment), its prognostic utility both during treatment and immediately following treatment have not systematically been evaluated in a large MCL patient cohort to support its use in clinical practice. Methods: We conducted a two-center (JTCC & UPenn), retrospective cohort study to examine the prognostic utility of pre-treatment (PET-1), interim-treatment (PET-2 after 2–3 treatment cycles) and post-treatment PET-CT (PET-3) imaging in a uniform MCL patient cohort undergoing dose-intensive chemotherapy (R-HCVAD) or high-dose chemotherapy followed by autologous stem (ASCT) cell rescue in the 1st line setting. The primary study endpoints were PFS and OS. PET-CT images were centrally reviewed for the purposes of this study using standardized response criteria proposed by the Imaging Subcommittee of International Harmonization Project in Lymphoma (Juweid et al, JCO 2007). Radiologists were blinded to clinical outcomes at the time of PET-CT review and results were dichotomized at each time point and their concomitant SUV max at a suspected site of disease was recorded. Result: 82 pts (median age 61, range 35–95) with advanced stage (98% stage IV) MCL with PET-CT data were identified for this analysis. Of these, 57 pts were treated with R-HCVAD (50) or ASCT (7) in the first-line setting. 154 PET-CT scans were reviewed. Overall treatment response rate (IWG) was 93% (76% CR + 17%PR). With median follow-up of 23 months (disease progression) and 27 months (overall survival), 3 year PFS and OS estimates were 70% (CI 53–82%) and 82% (CI 65–91%) respectively. Median baseline characteristics: WBC 7.4, ECOG PS 1, LDH/ULN .82, Ki-67 (MIB-1) 28% (range 10–90%), MIPI 3.5 (31% intermediate risk, 19% high risk). 20% and 30% of pts were blastoid variant and leukemic phase at diagnosis respectively. Pre-treatment PET-CTs were FDG-avid in 92% of MCL patients with a median SUV max of 7.8 (range 2.4–36.7) at a suspected site of disease. Pre-treatment PET-CT SUV max was positively associated with high Ki-67 (variance-weighted least-squares regression, p=.01). PET-2 and PET-3 were positive in 34% and 18% of patients respectively. Kaplan Meier and Cox regression survival analyses were used to test the association between PET-CT and survival. Interim PET-CT status was not associated with PFS (HR 1.1, CI .4-3.6, p=.8) or OS (HR .8, CI .15-4.6, p=.8). Post treatment PET-CT status was statistically significantly associated with PFS (HR 5.4, CI 2.0–14.5, p=.001, Harrell's C =.70, Figure) and trended towards significant for OS (HR 3.2, CI .8-11.9, p=.1). Post treatment PET-CT status remained an independent predictor of PFS in multivariate analysis which included MIPI score, blastoid variant and Ki-67. Conclusion: Our cohort is the first large series of MCL patients treated essentially with R-HCVAD examining the correlation between PET-CT and outcome in the front-line setting. A positive PET-CT following the completion of therapy identifies patients with an inferior PFS and a trend towards inferior OS. These data do not support the prognostic utility of PET-CT in pre-treatment (no upstaging) and interim treatment settings. This information should be incorporated into the design of future prospective clinical trials. We are currently examining the relationship of novel computer-assisted quantitative FDG-PET/CT measures of total tumor volume and total tumor metabolic burden with clinical outcome in patients with mantle cell lymphoma. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4204 Introduction: Most patients with asymptomatic advanced-stage low grade follicular lymphoma (FL) are managed by a ”watch and wait” strategy until they develop disease related symptoms or significant progression in tumor volume. The median time to first treatment (TFT) has been reported to be about 30 months from initial diagnosis (Ardeshna et al., Lancet 2003; 362: 516–22). Various prognostic factors such as FLIPI have been developed to estimate progression free survival and overall survival, but predictors for TFT from diagnosis have not been well defined in this population. The optimal frequency of follow-up and surveillance imaging remains unclear. Methods: We reviewed our institutional database of FL patients who underwent [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) or FDG-PET imaging at diagnosis or as part of follow-up imaging during the ”watch and wait” period. Only patients with FL with low grade histologies (grade 1 or 2) on tissue biopsy who were untreated prior to FDG-PET imaging and with a minimum of 6 months of follow-up after the imaging were included in the analysis. SUVmax was defined as the highest lesional SUV on each scan and was determined by a nuclear medicine physician. ROC curve analysis was used to identify SUVmax cutoff values which would best predict short (≤ 6 months) vs. long (〉 6 months) TFT with clinically relevant sensitivity and specificity for a training set of patients. The SUVmax cutoff value was then tested in another set of patients for the ability to categorize patients by TFT ≤ 6 months vs. 〉 6 months from imaging. Comparison between the two groups was performed using the Fisher's exact test. STATA 10.1 software was utilized for data analysis. Results: 78 FL patients followed in our institution from 2001 until 2011 were included in the study. In the training set of 27 patients (median age 52 years, range 19–67), the ROC curve analysis revealed that an SUVmax cutoff at 10 could distinguish between those with TFT ≤ 6 months vs. 〉 6 months. When applied to the test set of 51 patients (median age 53, range 18–82), an SUVmax ≥ 10 was able to predict short TFT correctly in 14 out of 16 patients who required treatment ≤ 6 months from the FDG-PET or FDG-PET/CT scan (positive predictive value of 88%). SUVmax ≥ 10 had a high specificity in the test set (90%), but limited sensitivity (47%). A Fisher's exact test (two sided) confirmed that the association between SUVmax ≥ 10 and short vs. long TFT groups was statistically significant (p=0.006). Conclusion: SUVmax ≥ 10 on FDG-PET or FDG-PET/CT imaging in patients with low grade FL can be used to identify those who will have a short TFT. An SUVmax cutoff at 10 could be an important factor in determining the frequency of clinical and imaging follow-up in asymptomatic, advanced-stage low grade FL patients who are managed by a ”watch and wait” strategy. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: High-grade B cell lymphoma (HGBCL) with rearrangements of MYC in addition to either BCL2 or BCL6 (DHL) generally has a poor prognosis for response to conventional therapies. Nevertheless, current studies of responses to anti-CD19 CAR-T cell therapies (CAR-T) have not demonstrated poorer overall response rates (ORR) in patients with DHL (Locke Lancet Oncol 2019, Schuster NEJM 2019). Double expressor diffuse large B-cell lymphoma (DEL), which lacks the chromosomal rearrangements of DHL but overexpresses MYC and BCL2 proteins by immunohistochemistry, has been similarly associated with poor outcomes, including after autologous and allogeneic stem cell transplantation (Herrera JCO 2017; Kawashima Biol Blood Marrow Transplant, 2018). DEL and DHL each have a different cell of origin and biology; DEL is typically activated B cell-like phenotype, whereas DHL typically have germinal center-like phenotype. To our knowledge, the association of DEL and outcomes with CAR-T has not been assessed. We aimed to assess whether DEL is associated with outcome after CAR-T. Methods: We retrospectively reviewed the records of 75 consecutive patients with aggressive B-cell lymphomas treated with commercial CAR-T therapy at the University of Pennsylvania between April 2018 and October 2019. We included all patients with either diffuse large B cell lymphoma or HGBCL who had both: a) fluorescence in situ hybridization testing for MYC, BCL2 and BCL6 chromosomal rearrangements, and b) immunohistochemical staining (IHC) for MYC and BCL2. Patients who had both MYC and BCL2 and/or BCL6 chromosomal rearrangements were classified as DHL; patients with IHC expression of both MYC in 〉 40% and BCL2 in 〉 50% of tumor cells without meeting criteria for DHL were classified as DEL. Patient characteristics were collected. Fisher's exact test was used to compare overall response rate (ORR) and log-rank test was used for comparison of progression-free survival (PFS). Results: Seventy-five eligible cases of aggressive B-cell lymphoma were identified; 9 were excluded due to non-DLBCL or HGBCL subtype and 16 were excluded due to insufficient characterization of tissue to assess DHL and DEL status. Fifty patients were eligible for analysis; 18 patients (36%) met criteria for DEL, 10 patients (20%) met criteria for DHL, and the remaining 44% of patients had neither DEL nor DHL (non-DEL/DHL). Tisagenlecleucel was administered to 39 patients, whereas axicabtagene ciloleucel was administered to 11 patients. Median age at leukapheresis was 65 years (range: 35-81). LDH, administration of bridging therapy, and ECOG performance status (PS) did not significantly differ between the three groups. Median follow-up for the entire cohort was 15.9 months. For all patients, best ORR was 54% (27/50 patients), median PFS was 3.7 months (95%CI: 2.8-NE), and median OS was not reached. Best ORR was 56% (10/18) for DEL patients, 50% (5/10) for DHL patients, and 55% (12/22) for patients with non-DEL/DHL. ORR did not differ between these groups (p=1.0). There was no difference in PFS (see Figure, p=0.90), OS (p=0.61), or RD (p=0.38) between the three groups. At 16 months, 69% of responding DEL continue in CR (95%CI: 30-89%), 72% of non-DEL/DHL (95%CI: 35-90%) continue in CR, and 100% of DHL (95%CI: NE) continue in CR. Conclusions: The proportion of patients with DEL in our study was similar to that reported for patients with diffuse large B-cell lymphoma in the literature. There were no significant differences between DEL, DHL, and non-DEL/DHL groups with regard to the proportion of patients with elevated LDH, bridging therapy, or ECOG PS. Although DHL and DEL have a negative prognostic impact on response to salvage therapies and hematopoietic stem cell transplant, neither DHL nor DEL status was associated with inferior response to anti-CD19 commercial CAR-T products. We demonstrate that patients with DEL can achieve prolonged responses after CAR-T. Moreover, neither DEL nor DHL status appeared to impact PFS, OS, or RD outcomes after commercial CAR-T. Figure Disclosures Chong: BMS: Membership on an entity's Board of Directors or advisory committees; Tessa: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; KITE Pharma: Membership on an entity's Board of Directors or advisory committees. Landsburg:Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Triphase: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Gerson:Loxo: Research Funding; Genentech: Consultancy; Pharmacyclics: Consultancy; Abbvie: Consultancy. Svoboda:Atara: Consultancy; Genmab: Consultancy; TG: Research Funding; Adaptive: Consultancy; Astra-Zeneca: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Imbrium: Consultancy; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding. Dwivedy Nasta:Merck: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; Debiopharm: Research Funding; Forty Seven: Research Funding; Incyte: Research Funding; Atara: Research Funding; Rafael Pharmaceuticals: Research Funding. Barta:Atara: Honoraria; Pfizer: Honoraria; Janssen: Honoraria; Seattle Genetics: Honoraria, Research Funding; Monsanto: Consultancy. Garfall:Novartis: Research Funding; Tmunity: Consultancy, Other: Personal fees, Research Funding; Amgen: Research Funding; Kite Pharma: Other: Personal fees; Janssen: Consultancy, Research Funding; GSK: Consultancy; Surface Oncology: Consultancy. Ruella:UPenn/Novartis: Patents & Royalties; Abclon, BMS, NanoString: Consultancy; Abclon: Consultancy, Research Funding. Frey:Amgen: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Syntax: Consultancy, Honoraria. Porter:Incyte: Other: Advisory board; Novartis: Honoraria, Other: Advisory board, Patents & Royalties: CAR T cells for CD19+ malignancies, Research Funding; Janssen: Other: Advisory board; Genentech/Roche: Current equity holder in publicly-traded company, Other: Spouse employment (ended Sept 2020); her salary includes stock/options; Glenmark: Other: Advisory board; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; American Board of Internal Medicine: Other: Member, exam writing committee (end date Oct 2019); Tmunity: Patents & Royalties; Adicet bio: Other: Advisory board; Kite/Gilead: Other: Advisory board. Schuster:AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria; Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding.