Abstract: Background: Early progression of disease (POD) in patients (pts) with mantle cell lymphoma (MCL) following intensive frontline treatment has been associated with inferior survival (Dietrich et al Ann Oncol 2014 and Visco et al Br J Haematol 2019), but the optimal time point to define early POD and the predictive significance of early POD following less intensive frontline treatment is not well established. We compare outcomes after all frontline treatments in a large MCL cohort categorized by time to progression and describe outcomes by class of second line treatment for pts with primary refractory disease. Methods: Clinical and outcome data for MCL pts treated between 2000 and 2017 were collected from 12 US centers. Overall survival (OS), defined from time of 1st progression, and secondary progression free survival (PFS2), defined from 1st progression to 2nd progression or death, were estimated by Kaplan-Meier and compared by log-rank test. Univariable and multivariable analyses were performed using Cox proportional hazards models for OS. 95% confidence intervals were calculated for all estimates and displayed in square brackets. We defined intensive treatment as high dose cytarabine in frontline therapy and/or autologous stem cell transplant in 1st remission. Pts were categorized into three groups: (a) refractory disease to frontline therapy or POD within 6 months of frontline therapy was termed primary refractory (PRF); (b) POD between 6 to 24 months of therapy was termed POD24 and (c) POD beyond 24 months was termed POD & gt;24. Salvage therapy was categorized as chemoimmunotherapy (CIT) for pts treated with CIT alone, BTK inhibitor (BTKi) for pts treated with BTKi single agent or in combination, and lenalidomide / bortezomib for pts treated with one or both agent +/- anti-CD20 therapy. Results: Of 1,168 pts with MCL, 457 pts had relapsed and were included in this analysis. The median age was 62, 77% were male, and ECOG PS was 0/1 in 94%. Median follow-up was 2.6 years (yr) after first progression. The most common induction regimens were R-HyperCVAD (26%), R-CHOP (24%), bendamustine and rituximab (19%), and R-M-CHOP (10%). Frontline treatment was intensive in 54%. Sixty five pts (14%) were PRF, 153 (34%) had POD24, and 239 (53%) had POD & gt;24. Additional baseline characteristics and comparison between groups are summarized in Table 1. The median OS was 1.3 yr [0.9-2.4] for PRF pts, 3 yrs [2-6.8] for POD 24, and 8 yrs [6.2-not reached (NR)] for POD & gt;24 (p & lt;0.0001). Comparing median PFS2 by time to POD, median PFS2 was 1 yr [0.4-1.3] for PRF, 1 yr [0.8-1.4] for POD24 and 2.3 yrs [1.8-3.2] for POD & gt;24 pts (p & lt;0.0001). Among PRF pts, median OS was 0.9 yr [0.4-3] for intensive treatment pts versus 2.0 yrs [0.9-4.5] among less intensive treatment (p=0.33). Among POD24 pts, median PFS2 was 0.8 yr [0.5-1] following intensive vs 2 yrs [0.8-2.9] with less intensive treatment (p=0.0003); likewise OS was shorter after intensive vs less intensive treatment, median 2 yrs [1.1-3.4] vs 6.8 yrs [3.1-9.7] (p=0.05). Both PRF and POD24 were associated with inferior OS on univariable analysis (Table 2) and remained associated with inferior OS on multivariable analysis independent of MIPI score and B symptoms (sx); HR 7.7 [3.9-15.1] for PRF and HR 2.5 [1.4-4.5] for POD24, HR 2.5 [1.4-4.5] for high MIPI score, and HR 1.3 [0.8-2.2] for B sx. Among pts with PRF MCL, median PFS2 and OS were 1.2 [0.5-2.3] and 2.4 [0.7-4.5] yrs for BTKi (n=21), 0.5 [0.2-2.3] and 1.1 [0.5-NR] yrs for CIT (n=22), and 0.3 [0.1-0.6] and 1.9 [0.1-2] yrs for lenalidomide / bortezomib (n=8) as 2nd line therapy. Two pts with PRF MCL received no further therapy and both died within one month of POD. Conclusions: Time to relapse is predictive of outcome in pts with MCL and outcomes with current salvage therapies are poor for pts with relapse within 6 months of frontline therapy. Of currently available second line therapies, BTKi were associated with improved PFS2 in refractory pts. Outcomes are particularly poor for pts who receive intensive induction therapies yet still relapse early, representing a population at high risk for early mortality related to MCL. Novel treatment approaches should be evaluated in this population, including CAR-T cell therapy, and attempts to improve risk stratification at diagnosis and develop improved therapies for high-risk pts should continue. Disclosures Maddocks: Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Merck: Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees. Kolla:Amgen: Equity Ownership. Bachanova:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Research Funding; Novartis: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Celgene: Research Funding; GT Biopharma: Research Funding. Gerson:Abbvie: Consultancy; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Merck: Research Funding; Mundipharma: Honoraria; Bayer: Consultancy, Research Funding; Seattle Genetics: Honoraria, Research Funding; Takeda: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Mundipharma: Honoraria. Hill:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Martin:Karyopharm: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Teneobio: Consultancy. Danilov:Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Bristol-Meyers Squibb: Research Funding; Aptose Biosciences: Research Funding; Bayer Oncology: Consultancy, Research Funding; TG Therapeutics: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; MEI: Research Funding; Janssen: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Takeda Oncology: Research Funding; AstraZeneca: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Grover:Seattle Genetics: Consultancy. Karmali:Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau. Ghosh:AstraZeneca: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; SGN: Consultancy, Honoraria, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Research Funding; Forty Seven Inc: Research Funding. Park:BMS: Consultancy, Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Hamadani:Pharmacyclics: Consultancy; Merck: Research Funding; Celgene: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Janssen: Consultancy; Otsuka: Research Funding; Medimmune: Consultancy, Research Funding; Takeda: Research Funding. Kahl:BeiGene: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy. Flowers:Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy; Denovo Biopharma: Consultancy; National Cancer Institute: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Bayer: Consultancy; AbbVie: Consultancy, Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Karyopharm: Consultancy; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy. Cohen:LAM Therapeutics: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Astra Zeneca: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; ASH: Research Funding; Lymphoma Research Foundation: Research Funding; Hutchison: Research Funding; UNUM: Research Funding.

Abstract: Introduction: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent-behaving disease can safely defer treatment (Calzada et al, 2018). In this subgroup, a lack of evidence to support the decision-making behind the choice of therapy has led to a wide diversity in treatments. We evaluated the importance of treatment intensity in patients with MCL who defer initial therapy. Methods: We included patients ≥ 18 years old with MCL from 11 academic centers and defined the deferred subgroup as patients who started therapy ≥ 90 days after diagnosis. Patients who received high dose cytarabine as part of their induction or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy while all other approaches were non-intensive. We identified differences between the baseline characteristics of the two groups using Fisher's exact tests, chi-squared tests, and t-tests as appropriate. We calculated progression-free (PFS) and overall survival (OS) from the date of diagnosis using the Kaplan-Meier method and compared the two groups using the log-rank test. Univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Results: Of 968 identified patients with MCL, 233 did not initiate therapy within 90 days of diagnosis and were considered deferred. Deferred patients had a lower Ann Arbor stage (p 〈 0.001), Ki-67 (p 〈 0.001) and LDH (p=0.007) at diagnosis compared to patients undergoing immediate treatment. Within the deferred group, 80 patients received intensive therapy (including 59 who completed ASCT in first remission), 99 received non-intensive therapy, and the remaining 54 patients did not receive any documented treatment and were excluded from this analysis. The most common intensive regimens included R-HyperCVAD and R-CHOP, and the most common non-intensive regimens included R-bendamustine and R-CHOP without ASCT. There was no difference in time to treatment, ECOG performance status, ethnicity, Ann Arbor stage or presence of B-symptoms between the two groups. However, patients who received non-intensive therapy were older (p 〈 0.001), more likely to have a normal LDH (p=0.03), and more likely to be treated at the reporting academic center (p=0.008). There was no significant difference in OS (Figure 1A, p=0.7) or PFS (Figure 1B, p=0.16) between the deferred patients who subsequently received non-intensive vs. intensive therapy. Univariate analysis of PFS highlighted the significance of: LDH (HR 0.62, p= 0.04), lack of blastoid morphology (HR 0.53, p=0.032), treatment initiation at participating academic center (HR 0.43, p 〈 0.001), post-induction rituximab (HR 0.42, p=0.003), and higher baseline hemoglobin level (HR 0.90, p=0.038) as predictors of improved PFS. Multivariable analysis demonstrated that post-induction rituximab (HR 0.16, p=0.008) and treatment initiation at an academic center (HR= 0.17, p 〈 0.001) predicted improved PFS while pre-existing coronary artery disease (HR=5.28, p=0.015) was associated with decreased PFS. A univariate analysis found that lack of blastoid histology (HR 0.24, p 〈 0.001), normal LDH (HR 0.31, p 〈 0.001), increased baseline hemoglobin (HR 0.83, p=0.005), post-induction rituximab (HR 0.16, p=0.014), and treatment initiation at an academic center (HR 0.34, p=0.003) significantly improved OS. In a multiviariable analysis, lack of blastoid histology (HR 0.11, p 〈 0.001) predicted improved OS while pre-existing diabetes mellitus (HR 5.98, p=0.005) and age (HR 1.08, p=0.001) were significantly associated with inferior OS. Intensity of treatment was not significantly associated with PFS or OS in the univariate or multivariable models. Conclusions: Among this large group of MCL patients who deferred therapy, use of an intensive induction therapy did not improve OS or PFS compared to patients who received non-intensive treatments. Our findings suggest that other patient- and disease-related factors may affect PFS and OS in this patient subgroup. Prospective studies to evaluate tools incorporating these factors will be useful in identifying the optimal therapy approach for patients with MCL who have completed an initial period of observation. Disclosures Calzada: Seattle Genetics: Research Funding. Bachanova:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; GT Biopharma: Research Funding; Gamida Cell: Research Funding. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding. Danilov:Takeda Oncology: Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Astra Zeneca: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Bayer Oncology: Consultancy, Research Funding. Grover:Seattle Genetics: Consultancy. Karmali:Gilead: Speakers Bureau; AstraZeneca: Speakers Bureau. Hill:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Park:Rafael Pharma: Consultancy; BMS: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Speakers Bureau; BMS: Consultancy; Teva: Research Funding; Gilead: Speakers Bureau; Takeda: Research Funding; G1 Therapeutics: Consultancy; Teva: Consultancy. Blum:Novartis: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding; Morphosys: Research Funding. Hamadani:Cellerant: Consultancy; Celgene Corporation: Consultancy; MedImmune: Consultancy, Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Ostuka: Research Funding; Takeda: Research Funding; ADC Therapeutics: Research Funding; Merck: Research Funding; Janssen: Consultancy. Kahl:Genentech: Consultancy; Seattle Genetics: Consultancy; ADC Therapeutics: Research Funding. Flowers:Denovo Biopharma: Consultancy; Celgene: Research Funding; Spectrum: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Gilead: Research Funding; Pharmacyclics/ Janssen: Consultancy; BeiGene: Research Funding; Bayer: Consultancy; Pharmacyclics: Research Funding; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Abbvie: Research Funding; Gilead: Consultancy; Janssen Pharmaceutical: Research Funding; OptumRx: Consultancy; Genentech/Roche: Consultancy; Millennium/Takeda: Research Funding; Abbvie: Consultancy, Research Funding; Karyopharm: Consultancy; National Cancer Institute: Research Funding; Genentech/Roche: Research Funding; Acerta: Research Funding. Cohen:Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: 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; Celgene: 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; Janssen: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Takeda: Research Funding; BioInvent: Consultancy; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract: Introduction: Proteasome inhibitors (PI) and immunomodulatory drugs have become the backbone of therapy for multiple myeloma (MM). The oral boron-containing selective and reversible proteasome inhibitor ixazomib has shown to induce deep and durable responses (Kumar RK et la, Blood 2016. 128(20):2415-2422). Triplets containing ixazomib, has shown to be more efficacious than doublet regimens in the relapse setting (Moreau P, et al. N Engl J Med 2016. 374:1621-1634).However, to date, there is not companion diagnostics capable of predicting PI response. We have recently discovered that MM patients resistant to PI lack of the ankyrin (ANK) and death domain (DD) present in the 3'-end of NFKB2. Loss of NFKB2 3'end frequently resulted from a structural rearrangements. We found that NFKB2-ANK and -DD are crucial at initiating bortezomib's apoptotic signal by facilitating caspase-8 activation (unpublished data). Based on this findings, we designed this study to examine the efficacy of NFKB2 break apart FISH to predict the response to ixazomib and dexamethasone (Id) vs. ixazomib, lenalidomide and dexamethasone (IRd) in early relapse MM patients. Methods: In this phase 2 biomarker-driven open-label trial, relapsed patients with & lt;4 lines of therapy were randomized to ixazomib 4 mg weekly 3 of 4 weeks and 40 mg weekly dexamethasone vs. Id plus 25 mg of lenalidomide daily days 21/28, based on the status of NFKB2 rearrangement in plasma cells. Patients were screened for NFKB2 rearrangement detected by NFKB2 break apart FISH. Patients without NFKB2 rearrangement received Id and patients with NFKB2 rearrangement were subsequently randomized in a 1:1 fashion to receive Id or IRd. The primary endpoint is to compare the response rate (MR or better) of Id or IRd at 4 cycles according to the rearrangement status of NFKB2 Results: At the moment of the interim analysis, 60 patients have achieved 4 cycles of treatment. All treatment groups (NFKB2 FISH [-] Id, n=27, NFKB2 FISH [+] Id, n=20 and IRd, n=19) received a median of 2 prior lines of therapy. A trend to higher ORR was observed in NFKB2 FISH negative treated with Id compared with NFKB2 FISH positive (41% CI:58%-97% vs. 30% CI:8%-60%, P=0.4, target p-value goal 0.15), including significantly higher rates of ≥ very good partial response, ≥ partial response, ≥ minimal response (15%, 25%, 15% vs. 4%, 25%, 10%, respectively). ORR for IRd arm is for now 57% CI:27%-80%. Interestingly, & gt;G3 treatment related adverse events were higher in Arm A (15%) and Arm C (13%) vs Arm B (0%). The most common (≥10%) ≥ grade 3 include URI/pneumonia 16% and diarrhea 12% in Id NFKB2 FISH negative vs. neutropenia 18% and diarrhea (10%) in the IRd NFKB2 FISH positive arm. Treatment discontinuations only occurred in 3 NFKB2 FISH positive Id treated patient (13%). Conclusion: Interim analysis demonstrates a trend higher efficacy and ≥G3 toxicity of ixazomib with dexamethasone in MM patients with negative NFKB2 break-apart FISH compared to those with a positive test. Efficacy and toxicity of the triplet regimen are comparable to what is seen in the Tourmaline 1 trial. This study is registered clinicaltrials.gov# NCT02765854 Disclosures Bernal-Mizrachi: Kodikaz Therapeutic Solutions: Consultancy, Current holder of individual stocks in a privately-held company, Patents & Royalties; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Winship Cancer Institute of Emory University: Current Employment; Bigene: Membership on an entity's Board of Directors or advisory committees. Nooka: Takeda: Consultancy, Research Funding; Janssen Oncology: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Other: Travel expenses; Sanofi: Consultancy; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy, Research Funding; Oncopeptides: Consultancy; Adaptive technologies: Consultancy; Karyopharm Therapeutics: Consultancy. Ye: Alexion, AstraZeneca Rare Disease: Other: Study investigator. Vij: BMS: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; BMS: Honoraria; GSK: Honoraria; Oncopeptides: Honoraria; Karyopharm: Honoraria; CareDx: Honoraria; Legend: Honoraria; Biegene: Honoraria; Adaptive: Honoraria; Harpoon: Honoraria. Hofmeister: Ohio State University: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: IP rights, Patents & Royalties; Medscape: Other: Non-pharma speaker for education, research, marketing; DAVA Oncology: Other: Non-pharma speaker for education, research, marketing; TRM Oncology: Other: Non-pharma speaker for education, research, marketing; Verascity: Other: Non-pharma speaker for education, research, marketing; Aptitude Health: Other: Non-pharma speaker for education, research, marketing; BlueBird Bio: Other: Non-CME speaker; Amgen: Other: Non-CME speaker; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Philips Gilmore: Other: CME speaker; Non-pharma speaker for education, research, marketing; BioAscend: Other: CME speaker; Imbrium: Membership on an entity's Board of Directors or advisory committees; Myeloma360: Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Local PI of CST; Oncolytics: Other: National PI for CST; PI or co-PI IST; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: Local PI of CST; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Local PI of CST; Nektar Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Local PI of CST; BMS/Celgene: Other: National PI for CST; PI or co-PI IST; Local PI of CST; Sanofi: Other: National PI for CST; PI or co-PI IST. Rushton: KSL: Current Employment. Lonial: Merck: Honoraria; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Kaufman: Incyte, celgene: Consultancy; Genentech, AbbVie, Janssen: Consultancy, Research Funding; Tecnofarma SAS, AbbVie: Honoraria; Heidelberg Pharma: Research Funding; Janssen: Honoraria; Novartis: Research Funding; Incyte, TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Fortis Therapeutics: Research Funding; BMS: Consultancy, Research Funding; Amgen: Research Funding; Roche/Genetech, Tecnopharma: Consultancy, Honoraria; Sutro, Takeda: Research Funding.

Abstract: Introduction Black (B) patients with Mycosis fungoides and Sézary Syndrome (MF/SS) have inferior survival and distinct clinical presentations, including many high risk features compared to non-black (NB) patients with MF/SS in large registry studies from the United States. We sought to characterize clinical differences in presentation, treatment, and outcomes to identify drivers of disparities among B patients with MF/SS. Methods We performed a retrospective review of 417 patients with MF/SS diagnosed between 1990 and 2020 at 6 academic institutions in the United States that serve populations with large numbers of Blacks and minorities. Patients with pathologic review and a confirmed histopathologic diagnosis of MF or SS with a stage & gt;1B as their highest TNMB stage were eligible for inclusion. The primary objective was to assess differences in clinical characteristics, treatment patterns, and survival between B and NB patients. Clinical variables included demographics, insurance, zip code, tumor characteristics, and treatment. Descriptive analysis was performed for each variable. Comparison between B and NB patients utilized ANOVA for numerical covariates and chi-square test or Fisher's exact test for categorical covariates. Kaplan-Meier curves for OS were generated, and subgroups were analyzed separated. Results Among 417 patients, 204 (48.9%) were Blacks, 196 (47.0%) were White, and (4.1%) were other races (8 Asian, 5 unknown, 4 Hispanic). The diagnosis was MF in 366 (87.8%), SS in 47 (11.3%), and other 4 patients. Stage at diagnosis was available for 384 patients. 37 (9.6%) were stage 1A, 165 (43%) were stage 1B, 34 (8.9%) were stage 2A, 58 (15.1%) were stage 2B, 44 (11.5%) were stage 3, and 46 (12%) were stage 4 at diagnosis. The median survival of the whole cohort (n=417) was B patients were younger (median 50.1 years in B vs. 60.5 in NB, p & lt;0.001), more often female (49.5% in B; 35.7% in NB, p=0.004), had higher rates of reported lymphadenopathy (78.5% vs. 70%, p=0.039), longer delays from symptom onset to diagnosis (2.0 years in Black vs. 1.2 years in NB, p=0.014), and higher rates of bacteremia at any time in their disease course (19.7% in Black, vs. 6.6% in NB, P & lt; 0.001) compared to NB patients. There was no difference in insurance status (private, Medicare/Medicaid, or uninsured) or comorbidities by race. There was also no differences in overall TNMB stage at diagnosis (p=0.14) compartment stage, or highest stage (p=0.076). Progression to a higher T, N, M, or B stage occurred at similar frequencies in B and NB patients (n=83 (43.2%) in Black and n=73 (38.8%) in NB, p=0.38). Time to first therapy, time to systemic therapy, or total lines of therapy also did not differ by racial group. A greater fraction of B compared to NB patients received systemic therapy but this did not reach statistical significance (72.6% in Black vs. 62% in NB, p=0.060). There was no difference in large cell transformation at any point, or white blood cell count (WBC), lactate dehydrogenase (LDH), or T-cell receptor (TCR) clonality in skin/blood at diagnosis. On univariate analysis, race was not associated with survival; the median survival was 10.5 years (95% CI 8-13.2) in B patients and 10.9 years (95% CI 7.2-14.1) in NB patients. Covariates associated with inferior survival included older age (p & lt;0.001), number of comorbidities (p & lt; 0.001), bacteremia (p & lt; 0.001), higher overall TNMB stage, higher individual T, N, M and B stage, progression to a higher N or M stage, positive TCR in the blood, WBC value, and LDH value. Insurance status and year of diagnosis (prior to 2010, vs. following 2010) were not associated with survival. On multivariate cox proportional hazard model, age at diagnosis, comorbidities, extra-cutaneous disease, bacteremia, TNMB stage at diagnosis, and progression to a higher nodal stage remained statistically significant for survival. Conclusions We present the first multicenter analysis of racial disparities in MF/SS, with nearly 50% B patients. B patients had distinct presentations, delay in diagnosis, and higher rates of bacteremia compared to NB patients. In contrast to US-registry studies, there was no difference in survival between B and NB patients. This finding could be explained by access to academic centers and/or higher rates of insurance coverage among B patients in our cohort. Additional analyses will be updated at the time of the presentation. Figure 1 Figure 1. Disclosures Allen: ADC Therapeutics: Consultancy; Kyowa Kirin: Consultancy; Secure Bio: Consultancy. Mehta: Seattle Genetics; Incyte; TG Therapeutics: Consultancy; Seattle Genetics; Incyte; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Affirmed; Kite/Gilead; Roche-Genetech; Celgene/BMS; Oncotartis; Innate Pharmaceuticals; Seattle Genetics; Incyte; Takeda; Fortyseven Inc/Gilead; TG Therapeutics; Merck; Juno Pharmaceuticals/Bristol Myers Squibb: Research Funding. Huen: Rhizen: Research Funding; Elorac: Research Funding; Kyowa Kirin: Research Funding; Tillium: Research Funding; Innate: Research Funding; Galderma: Research Funding; Miragen: Research Funding. Porcu: Viracta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Daiichi: Honoraria, Research Funding; Kiowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum: Consultancy; DrenBio: Consultancy.

Abstract: In the current study, the authors perform a retrospective analysis of overall survival (OS) and progression‐free survival (PFS) among patients with non–small cell lung cancer who were treated with single‐agent immune checkpoint blockade between 2013 and 2018. The data indicate similar outcomes between Black and White patients with regard to OS, PFS, and the rate of immune‐related adverse events. Large studies are needed to make these findings more generalizable.

Abstract: Clinical outcomes and predictors of survival in patients with newly diagnosed mantle cell lymphoma (MCL) treated in the rituximab era (2000–2015) at 12 US academic centers were assessed to identify determinants of survival across age groups. Objectives were to characterize and compare practice patterns, outcomes and prognostic factors for survival in younger patients (age  〈  65) and older patients (age ≥ 65 years). Among 1162 patients included, 697 were younger and 465 were older. In younger patients, 2‐year progression free survival (PFS) and overall survival (OS) rates were 79% and 92% respectively; blastoid histology, ECOG ≥ 2, and lack of maintenance rituximab (MR) remained statistically relevant to poor OS on univariate analysis (UVA) and multivariate analysis (MVA). In older patients, 2‐year PFS and OS rates were 67% and 86% respectively; lack of maintenance rituximab remained significantly associated with inferior PFS and OS on UVA and MVA ( p   〈  0.001). Two‐year PFS rates were 79%, and 67% and 2‐year OS rates were 92% and 86% for ages 〈 65 and ≥ 65 respectively ( p   〈  0.001). First‐line high‐dose cytarabine exposure and/or MR lessened the negative impact of age on survival. Taken collectively, survival outcomes for older patients remain inferior to those of younger patients in the rituximab era. However, maintenance rituximab and potentially high‐dose cytarabine‐based induction can mitigate the negative impact of age on survival.