Citations

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.

e19532 Background: The traditional approach to the treatment of early-stage classical Hodgkin lymphoma (cHL) has been combined modality therapy (CMT) with both chemotherapy and radiotherapy (RT). CMT has shown improved disease control, but RT can lead to long-term adverse effects, including secondary malignancies and cardiac toxicity. Multiple clinical trials have assessed treatment de-escalation strategies to chemotherapy-alone regimens, but results are conflicting. We aimed to assess the real-world implications of these trials by comparing patient outcomes based upon treatment with CMT or chemotherapy-alone. Furthermore, we proposed to assess differences in treatment outcomes stratified by disease bulk, favorable/unfavorable disease, and PET2 response. Methods: We conducted a retrospective, multi-center cohort study of consecutive adult patients with early-stage (stage IA-IIB) cHL treated between January 2010-December 2020. Baseline characteristics, treatment modality, and outcomes were abstracted by chart review. Available PET2 scans (n=110) were independently reviewed by a blinded nuclear radiologist. Deauville score (DS) ≥4 was characterized as positive (+), and DS≤3 negative (-). All analysis was conducted using intention-to-treat principles based upon the initial treatment plan (CMT or chemotherapy-alone). Results: In 125 patients [58% male, median age 34 (range, 18-78)] with early-stage cHL, CMT was intended in 63 (50%) patients, with chemotherapy-alone in 62 (50%). Bulky disease was observed in 43 (34%), unfavorable disease in 81 (65%), and 15 (14%) were found to be PET2+. With median follow-up of 59.8 months (95%CI, 48.6 to 71.0), 5 (4%) deaths occurred, and 17 (14%) patients had relapsed/refractory disease. No significant differences in overall survival (OS) were seen based upon treatment intention. However, there was substantially reduced progression-free survival (PFS) (Table) with chemotherapy-alone in the whole cohort, and also in those with bulky, unfavorable, and PET2+ disease. No significant PFS differences were seen based upon treatment intention for patients with non-bulky, favorable, or PET2- disease. Conclusions: Based on our real-world experience, CMT appears particularly beneficial for patients with bulky disease, unfavorable prognostic factors, and PET2+ disease. However, while recent trials showed a benefit of CMT in non-bulky, favorable and PET2- patients, chemotherapy-alone may be comparable for these patients in actual clinical practice.[Table: see text]

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.

Abstract Multiple clinical trials have assessed de-escalation strategies from combined modality therapy (CMT) to chemotherapy-alone for the treatment of early-stage classical Hodgkin lymphoma (cHL), confirming similar outcomes. The application of these data to the real-world is limited, however. We conducted a retrospective, multicenter cohort study comparing CMT vs chemotherapy-alone in patients with early-stage cHL (stage IA-IIB) treated between January 2010 and December 2020. Positron emission tomography (PET) scans after chemotherapy cycle 2 (PET2) were independently reviewed by a nuclear radiologist (Deauville score ≥4, positive; ≤3, negative). Patient outcomes were compared by using an intention-to-treat analysis. Among 125 patients (CMT, n = 63; chemotherapy-alone, n = 62) with a median follow-up of 59.8 months (95% CI, 48.6-71.0), no differences in overall survival were observed (5-year overall survival, CMT 98.0% vs chemotherapy-alone 95.1%; log-rank test, P = .38). However, there was reduced progression-free survival (PFS) with chemotherapy-alone among all patients (2-year PFS, CMT 95.1% vs chemotherapy-alone 75.3%; log-rank test, P = .005) and in those with bulky (n = 43; log-rank test, P &lt; .001), unfavorable (n = 81; log-rank test, P = .002), or PET2-positive (n = 15; log-rank test, P = .02) disease. No significant differences in PFS were seen for patients with non-bulky (log-rank test, P = .35), favorable (log-rank test, P = .62), or PET2-negative (log-rank test, P = .19) disease. Based on our real-world experience, CMT seems beneficial for patients with early-stage cHL, especially those with PET2-positive and unfavorable disease. Chemotherapy-alone regimens can lead to comparable outcomes for patients with favorable, non-bulky, or PET2-negative disease. We conclude that although results seen in clinical trials are replicated in certain patient subgroups, other subgroups not fitting trial criteria do poorly when radiotherapy is excluded.

Abstract Therapeutic strategies that target novel pathways are urgently needed for patients with relapsed/refractory multiple myeloma (RRMM). Ibrutinib is an oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in MM cells. This phase 1 dose‐escalation study examined various doses of ibrutinib in combination with standard doses of lenalidomide (25 mg) and dexamethasone (40 mg) using a standard 3 + 3 design in RRMM patients. The primary objective was to determine the maximum tolerated dose (MTD) of ibrutinib in combination with lenalidomide and dexamethasone. Patients ( n = 15) had received a median of 4 prior regimens, 53% were triple‐class exposed, 33% were penta‐exposed, and 54% were lenalidomide‐refractory. The MTD of ibrutinib was 840 mg ( n = 6) and only 1 dose‐limiting toxicity; a grade 3 rash possibly related to ibrutinib was noted. The most common ≥ grade 3 adverse events were rash in 2 (13%), lymphopenia in 2 (13%), leukopenia, neutropenia, thrombocytopenia, and anemia all occurring in 3 (20%) patients each. One patient achieved a partial response for an overall response rate of 7%. The clinical benefit rate was 80%. The median time to progression was 3.8 months. Ibrutinib, lenalidomide and dexamethasone appears to be a safe and well‐tolerated regimen with reasonable efficacy in heavily pretreated RRMM patients.

AbstractExtramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1% of cases and can be differentiated from infectious etiologies based on fluid cytology.

Extramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1 % of cases and can be differentiated from infectious etiologies based on fluid cytology.

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 Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) which targets CD20. This study evaluates the utilization and cost-effectiveness of (90)Y-IT in the first line treatment for patients with previously untreated low-grade FL (UFL) and marginal zone lymphoma (UMZL) treated at our institution with (90)Y-IT. Methods We utilized the Advanced Text Explorer (ATE) and the Lymphoma SPORE databases to identify two groups of patients with UFL, WHO grade 1-2, and UMZL who received treatment with either (90)Y-IT or bendamustine plus rituximab (BR) at Mayo Clinic Cancer Center between January 2003 and December 2019. We excluded all patients who had &gt;25% bone marrow involvement with lymphoma for the BR group as this was a requirement for (90)Y-IT treatment. Inverse propensity weighting was utilized to balance the groups for baseline patients and disease characteristics. We use progression-free survival (PFS) as a denominator for the cost effectiveness/utilization evaluation. We identified meaningful and retrospectively measurable outcomes to compare between the groups. we extracted the following data; number of clinic visits in the first year after therapy, emergency room visits, number of hospital admissions, number of hospitalization days, numbers of days on the floor and ICU, number of infections, number of neutropenic fever hospitalizations, number of C-difficile events, number of blood products transfusions, overall use of growth factors due to therapy induced neutropenia, average number of times a growth factor was used, and the number of therapeutic use days. We defined days of therapeutic use as the number of days a treatment was administered on. We also calculated the average cost of the induction treatment when utilizing either (90)Y-IT or BR. The therapeutic cost included only the cost of the medications/therapies and their administration. Results Our cohort consists of a total of 143 patients - 64% (92/143) received BR and 36% (51/143) received (90)Y-IT (see Table-1 for clinical characteristics).The median follow-up from the time of therapeutic administration for the (90)Y-IT group was 5.3 years (95% CI; 4.2, 6.2) with one death and 4.7 years (95% CI; 3.9, 4.9) for the BR group with 6 deaths. The ORR was 100% in (90)Y-IT group with 94% achieving complete response (CR) while ORR in the BR group was 98% with 95% achieving CR. Rituximab maintenance was utilized in 33% of BR patients compared to only 6% in patients who received (90)Y-IT, p=0.002. After utilizing inverse propensity weighting (Figure-1), 5 years PFS was 76% for the (90)Y-IT group and 75% for the BR group, p=0.63 (Figure-2). We evaluated the average treatment effect of (90)Y-IT compared to BR on utilization outcomes, Table-2. (90)Y-IT required an average of 4.5 clinic visits less within the first year after treatment compared to BR group, p&lt;0.001. (90)Y-IT patients had an average of 10 days less of therapeutic use days compared to the BR group, p&lt;0.001. Patienta had similar admission rates to the hospital in both groups. However, when patients were admitted to the hospital in the first year after treatment, those who received (90)Y-IT spent an average of 1.5 days less in the hospital compared to the BR group, p=0.046. The overall use of growth factors was 40% less in the (90)Y-IT group as compared to the BR group, p&lt;0.001. The therapeutic cost of induction of (90)Y-IT was 54% less than that of 6 cycles of BR. Transformation to a high grade of lymphoma was seen in 4 patients in the BR group and 2 patients in the (90)Y-IT group. There was only one case of myelodysplastic syndrome in the BR group and none in the (90)Y-IT group. Conclusion Radio-immunoconjugate therapy with (90)Y-IT is a very convenient and cost-effective treatment for low-grade UFL and UMZL. This is especially important amidst the COVID-19 pandemic as it requires less contact with the health system with decreased number of therapeutic days, clinic visits, use of growth factors and number of hospitalization days. The cost of the therapeutic agents and their administration was also significantly lower for the (90)Y-IT which could help reducing the burden on the health system. Figure 1 Figure 1. Disclosures Cerhan: Regeneron Genetics Center: Other: Research Collaboration; Genentech: Research Funding; Celgene/BMS: Other: Connect Lymphoma Scientific Steering Committee, Research Funding; NanoString: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy. OffLabel Disclosure: We are describing the use of Yttrium-90 ibritumomab tiuxetan in the first line setting in comparison to the bendamustine plus rituximab which is the standard of care

Introduction Cholangiocarcinoma is a rare malignancy accounting for 3% of gastrointestinal cancers in the USA. While multiple risk factors for cholangiocarcinoma are established, other potential risk factors are still controversial. Herein, we used a large national database to investigate possible risk factors and associations. Method We used the National Inpatient Sample database to review all admissions between 2011 and 2015. We grouped patients based on the presence and absence of cholangiocarcinoma. Using multivariate logistic regression analysis, we assessed the association between obesity, alcohol abuse, smoking, diabetes mellitus and cholangiocarcinoma. Results Out of 30 9552 95 admissions, 20 030 had cholangiocarcinoma. Cholangiocarcinoma patients were older (67 ± 12.8 vs. 57 ± 20.6; P < 0.001) and had fewer female patients (48 vs. 59%; P < 0.001). Multivariate logistic regression analysis showed that diabetes mellitus was associated with cholangiocarcinoma (OR, 1.04; 95% CI, 1.01–1.08; P < 0.001). On the other hand, alcohol, smoking and obesity were all inversely associated with cholangiocarcinoma (OR, 0.75; 95% CI, 0.69–0.81; P < 0.001), (OR, 0.75; 95% CI, 0.71–0.79; P < 0.001) and (OR, 0.71; 95% CI, 0.67–0.75; P < 0.001), respectively. In addition, compared to Whites, Hispanic and Asian/Pacific Islander races were more associated with cholangiocarcinoma (OR, 1.27; 95% CI, 1.21–1.34) and (OR, 1.79; 95% CI, 1.67–1.92) ( P < 0.001 for all), respectively, whereas African American race was inversely associated with cholangiocarcinoma (OR, 0.85; 95% CI, 0.81–0.89; P < 0.001). Conclusion Patients with a diagnosis of diabetes mellitus or from certain ethnic groups (Hispanic and Asian/Pacific Islander) are associated with increased risk for cholangiocarcinoma.