Iqbal, Madiha

Abstract Intravascular lymphoma (IVL) is a rare extranodal non‐Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003–2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS‐IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non‐CNS‐IVL patients with abnormal FDG‐PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS‐IVL and 63.5% (35/55) had non‐CNS‐IVL. CNS‐IVL group consists of clinically isolated CNS involvement (CNS‐only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M‐IVL) (14.5%; 8/55). Non‐CNS‐IVL group consists of clinically isolated skin involvement (skin‐only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P‐IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B‐cell IVL. Rituximab + high‐dose methotrexate‐based regimen were used in 75% (12/16) of CNS‐IVL patients and RCHOP in 60% (17/28) of non‐CNS‐IVL patients. Estimated 5‐year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin‐only IVL was associated with excellent survival. Platelet count <150x10 9 /L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.

7556 Background: The majority of R/R NHL progressions after CART involve pre-existing sites, suggesting a promising role for bridging radiotherapy (bRT). We assessed the local control rate of disease sites bridged with radiotherapy prior to CART and identified predictors of in-field recurrence. Methods: We retrospectively reviewed 35 patients with aggressive B-cell NHL who received bRT between leukapheresis and CART infusion between 2018 and 2021 at a multi-site single institution. bRT local control rate (LC), calculated based on the total number of irradiated sites, was defined from bRT end date. Progression-free survival (PFS) and overall-survival (OS) were defined from the date of CART infusion. In-field recurrence was defined as disease relapse occurring within the radiation planning target volume. Kaplan-Meier plots and cox regression modeling were used to estimate the desired output. Results: Median age of the cohort at time of CART infusion was 59 (range 19-73). The median equivalent 2 Gy dose (EQD2) administered was 23.3 Gy (range 4-41 Gy). The median time from end of bRT to CART infusion was 14 days (range 6-42). Five (14%) patients also received bridging chemotherapy with bRT. Among the 34 evaluable patients, 30 (88%) achieved an objective response (59% complete response and 29% partial response). At a median follow-up of 12 months, 1-year PFS was 48% and 1-year OS was 72%. No progression occurred beyond 240 days. On review of treatment plans and pre-treatment PET/CT scans, 59 sites were identified that received bRT prior to CART infusion. The median size and SUVmax of the irradiated sites were 8.7cm (range 1.5-22) and 13 (range 4-46), respectively. Of the 59 irradiated sites, 8 sites (13.6%) in 7 patients had in-field local recurrence, translating to 1-year LC of 84%. No in-field recurrence occurred beyond 180 days. Moreover, no local recurrence occurred in patients who received radiation to all known sites of active disease to EQD2> 30 Gy (n = 4 patients); these patients remained in remission except for 1 who experienced progression outside the bRT field. On univariate analysis, triple hit lymphoma (THL) (OR 22.8, 95% CI: 3.8-138.3; p < 0.001), tumor size (OR 1.25, 95% CI: 1.1-1.4; p < 0.001), specifically ≥ 9cm (OR 9.4, CI: 1.2-77.3; p = 0.036) and SUVmax (OR 1.1, CI: 1.02-1.15; p = 0.008), specifically ≥ 20 (OR 5.6, CI: 1.3-23.7; p = 0.018), were significantly associated with increased risk of in-field recurrence. On multivariate analysis, THL (OR 32.9, CI: 3.2-336.0; p = 0.03) and tumor size (OR 1.3, CI: 1.1-1.6; p = 0.01) retained significant association with in-field recurrence. Conclusions: Bridging radiotherapy prior to CART provides excellent and durable in-field local control for R/R B-cell NHL. Patients with triple hit histology and bulky disease are likely at higher risk of in-field recurrence and may benefit from higher doses of bRT.

e19049 Background: Prognosis of COVID-19 is poor in the setting of immunosuppression. Casirivimab/imdevimab (REGEN-COV), bamlanivimab, and sotrovimab are investigational monoclonal antibodies (MoAbs) authorized for treatment of mild/moderate COVID-19 for patients (pts) 12 years or older and who are at high-risk for progression to severe COVID-19. These neutralizing antibodies, against SARS-CoV-2 spike proteins, have been shown to decrease risk of progression to severe disease. Recipients of allogeneic stem cell transplants (allo-SCT) or chimeric antigen T cell therapy (CAR T cell) represent a high risk population. However, treatment outcomes with these MoAbs in these pts are not well described. Methods: This retrospective study included 33 consecutive adult pts who developed mild/moderate COVID-19 and received anti-spike SARS-CoV-2 MoAbs between December 2020 and November 2021. Allo-SCT (N=27) or CAR T cell (N=6) recipients were included, and outcomes were analyzed separately. Pts received REGEN-COV (N=19), bamlanivimab (N=11), or sotrovimab (N=1), missing (N=2). Results: In the allo-SCT cohort (N=27), median age at time of COVID-19 was 55 (23-76) years. Median time from allo-SCT to COVID-19 was 31 (22-64) months. Two pts received CAR T-cell therapy prior to allo-SCT. Diagnoses included leukemia or myeloid diseases (82%), lymphoma (11%), or myeloma (7%). Transplant characteristics are summarized (Table). Thirteen pts were vaccinated against SARS-CoV-2 prior to breakthrough COVID-19. Events considered included hospitalization due to COVID-19, disease progression, or death from any cause. The 6-month event-free and overall survivals were 81% and 91%, respectively. In the CAR T cell recipients cohort (N=6), 4 pts received axicabtagene ciloleucel for diffuse large B-cell or follicular lymphoma and 2 received brexucabtagene autoleucel for mantle cell lymphoma. The median follow-up was 8 (1-11) months. Two pts received autologous SCT prior to COVID-19. Median time from CAR T cell therapy to COVID-19 was 10 (3-24) months. Three pts were vaccinated prior to COVID-19. Only 1 pt was hospitalized due to severe COVID-19 requiring mechanical ventilation leading to death. Conclusions: These results show a potential benefit of MoAbs in high-risk pts, namely allo-SCT or CAR T cell recipients. Future studies should evaluate the role of prophylactic use MoAbs in these populations. A comparative analysis with a matched control cohort (who did not receive MoAbs) will be provided at the meeting. [Table: see text]

Abstract Polatuzumab vedotin (PV) is an antibody–drug conjugate targeting CD79b that is approved for patients with relapsed/refractory large B-cell lymphoma (LBCL). Patients who relapse after chimeric antigen receptor (CAR) T-cell therapy were not included in the registration study, and reports of PV use after CAR T cells are limited. This multicenter retrospective analysis included patients with LBCL who relapsed or progressed after CAR T-cell therapy and subsequently received PV with or without rituximab and bendamustine between July 2019 and May 2021. Response to treatment and progression were assessed based on the 2014 Lugano criteria. Fifty-seven patients were included in the study: 18 (32%) patients were primary refractory to CAR T-cell therapy, and 34 (60%) patients received PV-based therapy immediately after CAR T-cell therapy. PV was combined with rituximab in 54 (95%) patients and administered with bendamustine in 35 (61%) patients. A response was achieved in 25 (44%) patients, including complete remission in 8 (14%). No significant association between baseline characteristics and response was observed. After a median follow-up of 47 weeks (95% confidence interval [CI], 40-54), 46 (81%) patients had disease progression or died, and the median progression-free survival was 10 weeks (95% CI, 5-15). On a multivariate analysis, bone marrow involvement (hazard ratio, 5.2; 95% CI, 1.8-15; P = .003) and elevated lactate dehydrogenase levels (hazard ratio, 5.0; 95% CI, 1.4-16; P = .01) were associated with shorter progression-free survival. Studies aimed at better characterizing the intrinsic mechanism of resistance and identifying optimal consolidation strategies for these patients are warranted.

Abstract Introduction. About 60% of patients with large B-cell lymphoma (LBCL) relapse after standard of care (SOC) anti-CD19 autologous chimeric antigen receptor (CAR) T-cell therapy, CD19 downregulation representing a major mechanism of resistance. Therefore, agents able to target B-cell antigens other than CD19 could be clinically effective for these patients. Polatuzumab vedotin (PV) is an antibody-drug conjugate targeting CD79b, and approved by the FDA in combination with bendamustine and rituximab for patients with relapsed or refractory (r/r) LBCL. Patients who relapsed after CAR T-cell therapy were not included in the registration study, and reports of PV use after CAR T-cells in real world practice are very limited. Methods. This is a multi-center retrospective analysis of patients with LBCL who relapsed after SOC CAR T-cell therapy and subsequently received SOC PV with or without rituximab and bendamustine between 07/2019 and 04/2021. PV was given at the standard dose of 1.8 mg/kg IV every 3 weeks in all patients (except for one patient, who received 1.4 mg/Kg). Response to treatment and progression were defined according to 2014 Lugano criteria. Survival curves were calculated using Kaplan-Meier estimates, and were compared between subgroups using the log-rank test. Cox regression was used for multivariate analysis (MVA). Results. Fifty-four patients were included in the study: median age was 59 (range, 22-79 years), 38 (70%) were male, and 30 (56%) had an internal prognostic index score &gt; 3. Median number of systemic therapies before CAR T-cell therapy was 2 (range, 2-6), 16 (30%) patients previously had autologous stem cell transplant (SCT), and 2 (4%) had allogeneic SCT. Sixteen (30%) patients were primary refractory to CAR T-cell therapy, and median time from CAR T-cell therapy to PV was 5 months (range, 1-40 months). CD19 status at time of relapse after CAR T-cell therapy was assessed by immunohistochemistry and/or flow cytometry in 41 patients, and positive in 34 (83%); CD79b status was assessed in 14 patients, and positive in all cases (100%). Thirty-two (59%) patients received PV-based therapy immediately after CAR T cell therapy, while 22 (41%) had intervening treatments (median 1, range 1-5). At time of PV initiation, median absolute neutrophil count was 2.9 (range 0.5-19 X10 9/L), median platelet count was 87 X10 9/L (range 15-437 X10 9/L), median serum creatinine was 0.9 mg/dL (range 0.4-22 mg/dL), and 44 (81%) patients had elevated serum lactate dehydrogenase (LDH). The median number of PV cycles was 2 (range, 1-16): PV was combined with rituximab in 51 (94%) patients, and administered with bendamustine in 33 (61%). A response was achieved in 24 (45%) patients, including complete remission (CR) in 8 (14%) patients and partial remission in 16 (30%)(Figure A), with a median duration of response of 11 weeks (95%CI, 5-17 weeks). No significant association between baseline characteristics and response was observed. To date, 49 (91%) patients stopped PV: 38 (70%) due to progression, 7 (13%) because of CR/patient decision, 3 (6%) to proceed to allogeneic SCT, and 1 (2%) to proceed to an immunotherapy clinical trial (despite absence of progression). No patients stopped therapy because of toxicity. After a median follow up of 45 weeks (95% CI, 20-70 weeks), 44 (81%) patients progressed/died, and median PFS was 9 weeks (95% CI, 4-14 weeks). To date, 34 (63%) died, and median OS was 16 weeks (95% CI, 13-19 weeks)(Figure B). Causes of death included progression in 31 patients and transplant-related complications in 3. On univariate analysis, a shorter median progression-free survival (PFS) was observed for patients with bone marrow (BM) involvement (3 vs 10 weeks, p=0.002), prior central nervous system involvement (4 vs 10 weeks, p=0.02), and elevated LDH (6 months vs not reached, p=0.004). On MVA, the association was maintained only for BM involvement (hazard ratio [HR] 4.8; 95% confidence interval [CI] 1.6-12.5, p=0.004) and elevated LDH (HR 5; 1.4-16.7, p=0.01)(Figure C). Discussion. PV is safe and effective, but has short duration of response in r/r LBCL after anti-CD19 CAR T-cell therapy, except for patients with normal LDH. Studies aimed at better characterizing intrinsic mechanism of resistance, including upregulation of BCL2 family proteins, to favor the development of more effective PV-based combination strategies for these patients, are warranted. Figure 1 Figure 1. Disclosures Crombie: Roche: Research Funding; Merck: Research Funding; Abbvie: Research Funding; Bayer: Research Funding; Karyopharm: Consultancy; Incyte: Consultancy. Kamdar: Celgene (BMS): Consultancy; Adaptive Biotechnologies: Consultancy; Genentech: Research Funding; Kite: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; Genetech: Other; TG Therapeutics: Research Funding; SeaGen: Speakers Bureau; Celgene: Other; KaryoPharm: Consultancy; AbbVie: Consultancy. Hess: ADC Therapeutics: Consultancy; BMS: Speakers Bureau. Neelapu: 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 Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; 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. Lin: Novartis: Consultancy; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Gamida Cell: Consultancy; Sorrento: Consultancy; Legend: Consultancy; Takeda: Research Funding; Merck: Research Funding; Vineti: Consultancy. Strati: Astrazeneca-Acerta: Research Funding; Roche-Genentech: Consultancy.

Abstract Background: AHCT is a standard of care treatment for eligible patients (pts) with MM. Most consensus guidelines recommend that at the time of first AHCT, enough APBHC should be collected to perform two AHCT. However, recent studies have shown that with each decade after 1990, the use of cryopreserved APBHC for a salvage AHCT has declined and is now in the range of 4.6-15% in the decade between 2010-2018. The collection and storage of APBHC for two AHCT incurs additional costs and a prior single center cost analysis revealed that having had collected for just one AHCT in a cohort of 726 MM pts would have saved 3.8 million USD between 1993 and 2011. 1 Most centers that perform AHCT for MM pts continue to collect and store PBAHC for 2 AHCT. Herein we evaluate utilization trends and costs associated with cryopreserved APBHC in patients with MM. Methods: We retrospectively evaluated the clinicopathologic data from 440 patients with MM who underwent APBHC mobilization and collection at Mayo Clinic Florida between 2010 and 2019. The number of apheresis/collection sessions and APBHC product collection yields were determined for patients who were mobilized by any method. We estimated the costs involved in PBSC collection (apheresis) and cryopreservation storage based on our institution-specific charges as of May 2021. The cost of 1 session of APBHC collection/apheresis was $4,680 and the cost of 1 year of APBHC cryopreservation was $4,790 per patient. Statistical analysis was performed using JMP Pro 15 (SAS). Chi-square and Fischer exact tests were used to carry out univariate analysis for categorical variables and Wilcoxon rank sum/Kruskal Wallis for continuous variables. Results: Patient demographics are shown in Table 1. 440 pts underwent at least one collection session and 347 underwent at least 1 AHCT. The median number of mobilization sessions was 1 (95% CI 1.0-1.03), the median number of collection/apheresis sessions was 2.0 (95% CI 2.39-2.59), 84.3% (n=371) required ≥1 collection session. The median number of CD34 stem cells collected was 7.6 x10 6 (95% CI 7.76-8.19 x10 6), and the median number of infused CD34 cells was 4 x10 6(95% CI 4.13-4.37x10 6). The median cost of total collection sessions (defined as # of apheresis/collection sessions x $4,680) was $9,360 per pt (95% CI $11,181-$12,100). The median cost of cryopreservation (defined as # of years of storage x $4,790) was $19,160 per pt (95% CI $9,682-$22,252). The median number of years of storage was 4 (95% CI 4.11-4.65). 77(17.5%) pts have had APBHC in storage for &lt;2 years, 218 (49.5%) have had APBHC in storage for 2-5 years, and 145 (33%) had have APBHC in storage for &gt;5 years. The median time from MM diagnosis to AHCT was 9.0 months (range 13.8-18.5). 82% of patients collected enough APBHC (≥6x10 6, at least 3x10 6 per AHCT)for 2 AHCT. 8% of patients had all APBHC infused during their first AHCT, 83.5% had half of their APBHC infused during their first AHCT, and 8.1% had a different amount of APBHC infused during their first AHCT thus 91.6% of patients who collected APBHC had cells in storage. The median OS for the entire cohort after AHCT was 94.7 months (95% CI 88.6-100). Out of 347 patients who had stem cells in cryopreservation, 5 (1.4%) underwent a salvage AHCT and 3 (0.9%) underwent a tandem AHCT. 61% percent of patients had ≥1 excess collection sessions for APBHC that ultimately went unused. The median cost of excess collection sessions was $4,680 per pt (range, $4,680-$32,760) and the median total cost for excess collection sessions plus costs for storage was $23,840 per pt (range, $4,680-$85,450). The sum of costs of excess collection sessions was $2,077,920 and the sum of costs of cryopreservation was $5,812,665. Conclusion: The results of this single center analysis show that only 1.4% of patients underwent a salvage AHCT between 2010 and 2019 while 91.6% had APBHC left in storage which confirms the increase in storage of cryopreserved APBHC and declining trend in the use of stored APBHC for salvage AHCT in pts with MM. This is likely due to the advent of next generation novel therapies such as monoclonal antibodies, proteasome inhibitors and immunomodulatory agents. Excess collections, and cryopreservation of unused APBHC incur a cost of nearly $8 million. Institutional policies regarding universal APBHC collection and long-term storage should be reevaluated. 1Phipps C, et al. Bone Marrow Transplantation 2015:50;663-667. Figure 1 Figure 1. Disclosures Murthy: CRISPR Therapeutics: Research Funding. Ailawadhi: Sanofi: Consultancy; Medimmune: Research Funding; Genentech: Consultancy; Ascentage: Research Funding; Pharmacyclics: Consultancy, Research Funding; Xencor: Research Funding; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy; Beigene: Consultancy; GSK: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy; Cellectar: Research Funding; Karyopharm: Consultancy.

Abstract Introduction: Novel genetic classifications of diffuse large B-cell lymphoma (DLBCL) highlight the molecular complexity beyond cell of origin and provide new therapeutic implications. Next generation trials may incorporate novel agents for different genetic subtypes based on the pathogenesis mechanisms. For example, with the LymphGen classification, the MCD, BN2, ST2, and EZB subtypes are predicted to be susceptive to PI3K/mTOR targeting (Wright 2020). However, PI3K inhibitors have not been tested in the frontline, although data on the mTOR inhibitor everolimus were encouraging (Alliance 1085). We launched a phase 1/1b trial (NCT04323956) to investigate the feasibility of combining a novel PI3K inhibitor parsaclisib with standard R-CHOP immunochemotherapy and to seek an efficacy signal. Methods: Adult patients with newly diagnosed DLBCL were eligible if any of the following was present: 1) non-GCB subtype per the Hans algorithm; 2) expression of either Myc (≥40%) or Bcl2 (≥50%) by immunohistochemistry; or 3) MYC rearrangement by FISH. High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, regardless of morphology, was also eligible. All patients received parsaclisib plus R-CHOP. Phase 1 followed a 3+3 design and the primary endpoint was maximum tolerated dose (MTD) of parsaclisib. Dose levels tested were level 1 (20 mg QD, d1-10; starting level) and level 2 (20 mg QD, d1-14). MTD was defined as the dose level below the lowest dose that induced dose limiting toxicity (DLT) in at least one-third of patients. The primary endpoint in phase 1b is complete response (CR) rate by PET. Results: From July 2020 to June 2021, 15 patients were enrolled, 9 in phase 1 and 6 in phase 1b. The median age at diagnosis was 56 years (range 20-79), and 7 (47%) were female. One patient (7%) had ECOG PS ≥2, 7 (47%) had elevated LDH, 7 (47%) had &gt;1 extranodal site, 13 (87%) had stage III/IV, and 7 (47%) had high-intermediate or high risk International Prognostic Index. Pathology was DLBCL in 13 patients (2 with concurrent follicular lymphoma) and high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements in 2 patients. Four (27%) had non-GCB subtype, 7 (47%) had Myc or Bcl2 single expression, 8 (53%) had Myc/Bcl2 double expression, and 5 (33%) had MYC rearrangement (2 with concurrent BCL2 and/or BCL6 rearrangements). In phase 1, 3 patients were enrolled at dose level 1 and 6 patients were enrolled at dose level 2. No DLT was observed. Therefore, MTD was not reached, and dose level 2 was selected for phase 1b dose expansion. Six patients were enrolled in phase 1b to date. At the data cutoff date of 7/22/2021, 8 patients completed all 6 cycles of treatment, 1 competed 5 cycles, 3 completed 3 cycles, 2 completed 2 cycles, and 1 completed 1 cycle. Treatment-related adverse events (AE) are summarized in Table 1. The most common hematological AE included lymphopenia (60%), anemia (53%), neutropenia (53%), and thrombocytopenia (27%), and the most common non-hematological AE included nausea (67%), alopecia (40%), constipation (33%), fatigue (33%), dyspepsia (20%), and peripheral sensory neuropathy (20%). The most common grade 3 or 4 AE included lymphopenia (47%), neutropenia (33%), and anemia (13%). One 80-year-old female required parsaclisib dose reduction in cycle 3 and subsequent parsaclisib discontinuation as well as cyclophosphamide and doxorubicin dose reductions due to febrile neutropenia (no source of infection was identified). No other patients required dose reductions. The median follow-up was 3.7 months (range 0.8-10.7). Thirteen patients were evaluable for interim response by PET. The objective response rate was 92%, with 8 (62%) CR and 4 (31%) partial response (PR). One (8%) patient progressed before cycle 2 following a transient clinical response (shrinking palpable mass). Among those who achieved an objective response at interim, 7 patients were evaluable for end of treatment response and all 7 maintained a response, with 6 (86%) CR and 1 (14%) PR. Conclusions: Parsaclisib and R-CHOP combination therapy was generally well tolerated, with no DLT observed in phase 1 and no major safety concerns in both phase 1 and the ongoing phase 1b expansion. The preliminary efficacy signal of objective response appears encouraging in a small cohort of high risk patients. Parsaclisib plus R-CHOP can be an experimental arm for future frontline DLBCL trials investigating genetic subtype-driven novel therapies. Figure 1 Figure 1. Disclosures Wang: Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; InnoCare: Research Funding; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Genentech: Research Funding; MorphoSys: Research Funding; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. King: Celgene/BMS: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Tun: Gossamer Bio, Acrotech: Consultancy; Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding. Habermann: Seagen: Other: Data Monitoring Committee; Incyte: Other: Scientific Advisory Board; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Parsaclisib is an investigational agent used in this clinical trial.

Abstract Introduction: Intravascular lymphoma (IVL) is an extra nodal non-Hodgkin lymphoma with tropism for vascular endothelium. It is characterized by growth of large cells within the lumen of small to medium sized blood vessels. Central nervous system (CNS) and skin are predominantly involved. This report represents a retrospective single-institution review of IVL. Methods: We identified patients (pts) with IVL evaluated at Mayo Clinic Cancer Center between January 2003 and December 2018. Demographic, clinical, radiologic, pathologic, and therapeutic data were extracted. Statistical analysis of overall survival (OS) and progression free survival (PFS)] was performed using Kaplan-Meier method. Results: Total number of pts was 55; 22% (12/55) had CNS-only IVL, 14.5% (8/55) had CNS and non-CNS IVL, and 63.6% (35/55) had non-CNS IVL. Eighty seven percent (47/54) pts were B cell type, 11% (6/54) were T cell type, one pt had NK cell type IVL and another was unknown. Four pts were diagnosed by autopsy. Median age at diagnosis was 68 years (range, 40-85). Sixty-four percent were males. ECOG performance status was &lt;2 in 66%. The median follow-up time from diagnosis was 63 months [CI 95%, 9-NR], and 47% (26/55) were alive. The most common diagnostic biopsy sites were bone marrow (BM) 45% (25/55), skin 25% (14/55), and brain 29% (16/55). Twenty-nine patients had a PET scan. Seventy nine percent (23/29) had abnormal PET findings, with mean SUV of 8.6 (range 2.5-19.1). Of the 35 pts with non-CNS IVL, 76% (16/21) had abnormal PET; furthermore, the diagnosis was made with biopsies of the following sites: bone marrow 54% (19/35), skin 40% (14/35), lung 14% (5/35), liver 5.7% (2/35), spleen 2.8% (1/35), and omentum 2.8% (1/35). Forty-six percent (13/28) received CNS prophylaxis and ten percent (3/55) had relapse in CNS. Two out of the three pts who had CNS relapse had received CNS prophylaxis. The median time to CNS relapse in non-CNS IVL was 9 months. The most common first-line regimen was high-dose methotrexate+ rituximab containing regimen 62% (10/16) in IVL with CNS involvement and RCHOP (60%) (17/28) in non-CNS IVL. Seventeen percent of (8/48) pts received autologous stem cell transplant (ASCT) and 63% (5/8) pts were transplanted in first complete remission (CR1), and 3 pts after the first relapse. Median OS (mOS) for the whole cohort was 57 months, [CI 95%, 9-NR], and median PFS was 7 months [CI 95%, 2-NR]. There was no significant difference in mOS between groups; CNS-only IVL- 9 months (CI 95%, 1-NR), non-CNS IVL -62 months (CI 95%, 20-NR) vs combined CNS and non-CNS IVL- 4 months (CI 95%, 3-NR). mOS for those who received ASCT in CR1 was not reached (CI 95%, 10-NR) vs 51 months in non-transplant group (CI 95%, 3-NR) p=0.24. In pts with non-CNS IVL, there was no significant difference in mOS between CNS prophylaxis subgroup (NR: CI 95%, 57-NR) vs no-CNS prophylaxis subgroup (20 months: CI 95%, 0-NR), p=0.12. In those with CNS IVL mOS for early diagnosis (0-30 days from symptom onset to diagnosis was NR (CI 95%, 3-NR) vs mOS for late diagnosis (&gt;30 days {31-14,440})-5months (CI 95% 1-NR), p=0.29]. Conclusion: 1. BM was most frequently involved in our patients. We suggest that BM biopsy should be part of diagnostic testing when IVL is suspected. 2. Most cases are of B-cell linage, consistent with reported literature. All non-B cell cases were in non-CNS locations. 3. PET scans were abnormal in more than 70% of cases indicating that this imaging modality is vital in the diagnosis due to odd location and small size of lesions. 4.Overall prognosis in the literature was poor with most patients surviving &lt;1 year. Our cohort has mOS of 57 months. The reason(s) for better survival in our cohort could not be definitively determined. 5. CNS involvement had an overall trend towards poor prognosis; however, those diagnosed early had better outcomes; this did not reach statistical significance due to small sample size. 6. mOS was not reached for those transplanted CR1. There was a trend towards a better survival associated with CNS prophylaxis versus no prophylaxis in non-CNS IVL. 7. We suggest that CNS-centric therapeutic approach and intensive consolidation with ASCT should be considered in managing IVL. Figure 1 Figure 1. Disclosures Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Habermann: Incyte: Other: Scientific Advisory Board; Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy.

Abstract Background :COVID-19 adversely affects individuals with cancer. Several studies have found that seroconversion rates among patients with hematologic malignancies are suboptimal when compared to patients without cancer. Among patients with hematologic malignancies, seroconversion rates also appear to be influenced by recent treatment and the type of treatment they have received. Patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are immunocompromised due to impaired humoral and cellular immunity in addition to prescribed immunosuppressive therapy. Chimeric antigen receptor T-cell (CAR T) therapy is now widely used for NHL and MM, but little is known about seroconversion rates after COVID-19 vaccination among these populations. Current national guidelines recommend COVID-19 vaccination to be offered to CAR T recipients as early as three months thereafter. We retrospectively evaluated SARS-CoV-2 spike-binding IgG antibody levels following COVID-19 vaccination among NHL and MM CAR T therapy recipients. Methods:This retrospective study was conducted at three Mayo Clinic sites on NHL and MM patients that received CAR T infusions from Sept 2016 to June 2021. Baseline characteristics were ascertained from medical records. All NHL and MM patients who had received CAR T at any point and were alive at the time that the COVID-19 vaccine first became available were eligible for inclusion for antibody response evaluation. For antibody response to vaccination, antibody spike values &gt; 0.80 U/mL were considered positive. Results: Out of 104 CAR T infusions, 73 patients are alive at the time of this submission. We have had 7 patients with known COVID-19 pre-CAR T and all 7 are currently alive (5 have antibody titers and 2 have not been tested yet). Nineteen patients developed known COVID infection post-CAR T (13 alive and 6 deceased). The mortality of COVID post-CAR T in our sample was 31.5%. Furthermore, of the 13 patients that survived COVID-19, they received CAR T an average of 416 days prior to COVID-19 infection (median = 337, range = 54 - 1406); the 6 patients who died from COVID-19 had received CAR T an average of 250 days prior to COVID-19 infection (median = 164, range = 7 - 846). All 6 deceased patients did not receive COVID-19 vaccination pre-CAR T. Out of 17 CAR T patients tested for antibody spike titers post COVID-19 vaccination, 76.4% were able to mount an antibody response. More patients with MM had a higher titer response to the vaccine (&gt;250 U/mL) compared to the NHL counterparts (0.80-249 U/mL). All patients that received the vaccine, regardless of antibody response, were alive at the time of this submission. Conclusions:The majority of CAR T recipients with NHL and MM are able to mount an antibody response following COVID-19 vaccination in our relatively small sample. The frequency of seroconversion among CAR T recipients seems to be similar to patients with hematologic malignancy who had received a hematopoietic cell transplant reported elsewhere. These findings are limited by our small sample size and may be influenced by the timing of vaccination relative to CAR T. Furthermore, almost half of our patients received IVIG post CAR T which could potentially cause false positive antibody results as pooled immunoglobulin preparations may contain COVID-19 antibodies from vaccinated healthy donors. To better understand the characteristics of the immunologic response against SARS-CoV-2 in patients post-CAR T, larger multicenter studies exploring both humoral and cellular immunity will be needed. JEWN, MI and JM are co-first authors and PV, HM and AR are co-senior authors. Figure 1 Figure 1. Disclosures Munoz: Physicians' Education Resource: Honoraria; Seattle Genetics: Honoraria; Bayer: Research Funding; Gilead/Kite Pharma: Research Funding; Celgene: Research Funding; Merck: Research Funding; Portola: Research Funding; Incyte: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; Janssen: Research Funding; Millennium: Research Funding; Gilead/Kite Pharma, Kyowa, Bayer, Pharmacyclics/Janssen, Seattle Genetics, Acrotech/Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche.: Speakers Bureau; Pharmacyclics/Abbvie, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, BMS, Kyowa, Alexion, Beigene, Fosunkite, Innovent, Seattle Genetics, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, Beigene, Servier: Consultancy; Targeted Oncology: Honoraria; OncView: Honoraria; Kyowa: Honoraria. Bergsagel: Oncopeptides: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: human CRBN mouse; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Genetech: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Wang: Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; InnoCare: Research Funding; Novartis: Research Funding; MorphoSys: Research Funding; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Fonseca: Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy; AbbVie: Consultancy; Patent: Prognosticaton of myeloma via FISH: Patents & Royalties; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees; Scientific Advisory Board: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Amgen: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Mayo Clinic in Arizona: Current Employment; Celgene: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy. Palmer: Sierra Oncology: Consultancy, Research Funding; CTI BioPharma: Consultancy, Research Funding; Protagonist: Consultancy, Research Funding; Incyte: Research Funding; PharmaEssentia: Research Funding. Dingli: Novartis: Research Funding; GSK: Consultancy; Apellis: Consultancy; Alexion: Consultancy; Sanofi: Consultancy; Janssen: Consultancy. Kapoor: Sanofi: Research Funding; AbbVie: Research Funding; Takeda: Research Funding; Karyopharm: Consultancy; Cellectar: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding. Kumar: Roche-Genentech: Consultancy, Research Funding; Oncopeptides: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Beigene: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Merck: Research Funding; Carsgen: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Bluebird Bio: Consultancy; Antengene: Consultancy, Honoraria; Sanofi: Research Funding. Paludo: Karyopharm: Research Funding. Bennani: Kymera: Other: Advisory Board; Vividion: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Verastem: Other: Advisory Board. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Lin: Kite, a Gilead Company: Consultancy, Research Funding; Merck: Research Funding; Gamida Cell: Consultancy; Takeda: Research Funding; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding; Sorrento: Consultancy; Legend: Consultancy; Vineti: Consultancy. Murthy: CRISPR Therapeutics: Research Funding.