Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.

Global health education programs should strive continually to improve the quality of education, increase access, create communities that foster excellence in global health practices, and ensure sustainability. The COVID-19 pandemic forced the University of Minnesota’s extensive global health education programs, which includes a decade of hybrid online and in-person programing, to move completely online. We share our experience, a working framework for evaluating global health educational programming, and lessons learned. Over the decades we have moved from a predominantly passive, lecture-based, in-person course to a hybrid online (passive) course with an intensive hands-on 2-week requirement. The pandemic forced us to explore new active online learning models. We retained our on-demand, online passive didactics, which used experts’ time efficiently and was widely accessible and well received. In addition, we developed a highly effective synchronous online component that we felt replaced some of the hands-on activities effectively and led us to develop new and innovative “hands-on” experiences. This new, fully online model combining quality asynchronous and synchronous learning provided many unanticipated advantages, such as increasing access while decreasing our carbon footprint dramatically. By sharing our experience, lessons learned, and resources, we hope to inspire other programs likewise to innovate to improve quality, access, community, and sustainability in global health, especially if these innovations can help decrease negative aspects of global health education such as its environmental impact.

A 54-year-old Caucasian male with history of hypertension, hyperlipidemia, insulin-dependent diabetes mellitus, and chronic skin rash of 4 years presented to the emergency department with worsening rash and weight loss. Physical examination revealed diffuse erythematous rash, skin ulceration, bullae with associated paresthesia in the lower extremities, trunk, bilateral upper extremities, and palms and soles. A computed tomography (CT) scan with contrast showed a large, heterogenously enhancing pancreatic mass measuring 9.4 × 3.8 cm with surrounding low-attenuation soft tissue thickening. Blood tests showed hemoglobin A1C of 10.0%. Glucagon level was elevated to 2,178 (normal < 80 pg/dl). Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) from the pancreatic mass was suggestive of pancreatic endocrine tumor. The tumor cells were positive for synaptophysin, chromogranin, CD56, and pan-cytokeratin with focal positivity for glucagon, suggestive of glucagonoma. The patient underwent distal pancreatectomy along with splenectomy and cholecystectomy. The glucagon level normalized to 25 pg/dl within a week of tumor resection, and during his 6-week outpatient follow up, skin rash had completely resolved.

There is a paucity of large‐scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly‐diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60–88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale‐Geriatrics (CIRS‐G) score was 6 (range, 0–27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high‐dose methotrexate (HD‐MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R‐MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58‐month median follow‐up, median progression‐free survival (PFS) and overall survival (OS) were 17 months (95% CI 13–22 months) and 43 months (95% CI 31–56 months), respectively. Three‐year PFS and OS were highest with MTR (55% and 74%, respectively). With single‐agent methotrexate ± rituximab, 3‐year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS‐G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3‐year PFS was 65% versus 45% without maintenance (p = 0.02), with 3‐year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD‐MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.

Background Primary CNS lymphoma (PCNSL) is a rare non-Hodgkin lymphoma that is often associated with immunosuppressed states. The Epstein-Barr Virus (EBV) may play a role in tumor pathogenicity in some cases. The objective of this study was to examine the patient characteristics, tumor pathology, and survival outcomes associated with EBV tumor status in patients with PCNSL. Methods This was a retrospective subset analysis from 17 academic medical centers that included 439 patients of ages 60 years and above with PCNSL (David K et al. ASH 2020). The associations between EBV status and clinical or demographical variables were tested by Fisher's exact test, Wilcoxon rank-sum test, or CMH trend test. Kaplan-Meier estimator was used to estimate survival probability. Survival difference between groups was tested by log-rank test for statistical significance. Confidence interval of survival rate was calculated using Greenwood's formula. Results A total of 247 patients with available EBV status were included in this analysis. Median age was 71 (range 60-84) and 44.5% were male. Notably, none of the patients were HIV-positive. Twenty-five patients (10.1%) had EBV positive tumors as detected by EBER (EBV-encoded RNA) in-situ hybridization or LMP1 immunohistochemistry (IHC), 17 of which were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD) and 8 of which were not PTLD. All EBV-positive non-PTLDs were diffuse large B-cell lymphoma. Three (15%) SOT-related PTLDs were EBV-negative. Patient characteristics analyzed included age at diagnosis, sex, ECOG performance status, history of prior or concurrent malignancies, history of solid organ transplant or autoimmune disease, history of allogeneic stem cell transplant, and immunosuppressive treatment. Of these, only a history of solid organ transplant or autoimmune disease (P&lt;0.0001) and immunosuppressive treatment (P&lt;0.0001) were highly correlated with EBV-positivity; there were no other patient factors associated with EBV status. For patients with EBV-positive SOT-related PTLD, the most common immunosuppressive medications were mycophenolate (n=13), calcineurin inhibitors (n=11), and prednisone (n=9). Only 1 of the EBV-positive non-PTLD cases had a history of autoimmune disease and was on mycophenolate and hydroxychloroquine. Tumor characteristics analyzed included expression of C-MYC, BCL2, CD5, cell of origin markers (BCL6, MUM1, CD10), and CD20 through IHC, C-MYC and BCL2 translocation through FISH, histology, and involvement of brain parenchyma, CSF, spinal cord, and eyes. EBV-positive tumors were associated with low C-MYC (p=0.047) and BCL6 (p=0.0006) expression on immunohistochemistry, but not other factors. There were no significant differences in tumor characteristics between those with EBV-positive PTLD and EBV-positive non-PTLD. Among patients with PTLD, 30% (n=6) did not receive primary chemotherapy, and the most common treatment regimens were high-dose methotrexate (HD-MTX) with or without rituximab (n=5) and rituximab alone (n=3). However, there was no significant difference in outcomes among PTLD patients who received chemotherapy or those who did not. Among EBV-positive non-PTLD patients, only 12.5% (n=1) did not receive primary chemotherapy and the most common treatment regimens were methotrexate/rituximab/temozolomide (n=3) and HD-MTX with or without rituximab (n=3). There was no difference in overall or progression free survival between patients with EBV-positive and EBV-negative tumors, or in outcomes among SOT-related PTLD patients regardless of EBV status. However, patients with EBV-positive non-PTLD PCNSL had better overall survival compared to patients with EBV-positive PTLD and EBV-negative tumors (p=0.033, Figure). Conclusions In this large observational study of older patients with PCNSL, the incidence of EBV positive tumors was overall low and was most commonly associated with SOT-related PTLD. Mycophenolate mofetil was the most common immunosuppressive medication. In those without PTLD, there were no patient or tumor factors that were associated with EBV status. Unexpectedly, non-PTLD EBV-positive PCNSL had superior outcomes to EBV-positive PTLD and EBV-negative PCNSL. Future studies of EBV-positive non-PTLDs are warranted to further evaluate the potential impact of EBV latency and the immune response on the tumor microenvironment. Disclosures Reddy: BMS: Consultancy, Research Funding; Celgene: Consultancy; Abbvie: Consultancy; Genentech: Research Funding; KITE Pharma: Consultancy. Bachanova:Karyopharma: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; FATE: Research Funding; Incyte: Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Bond:Seattle Genetics: Honoraria. Goldlust:Tocagen: Membership on an entity's Board of Directors or advisory committees, Other: travel; BMS: Membership on an entity's Board of Directors or advisory committees, Other: travel; WEX: Consultancy, Other: travel; Cortice Bio: Consultancy, Other: travel; Boston Biomedical: Consultancy; COTA: Other; Novocure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel, Research Funding, Speakers Bureau. Spurgeon:Gilead: Research Funding; Genentech: Research Funding; Cardinal Health: Honoraria; Bristol-Myers Squibb: Research Funding; VelosBio: Consultancy, Research Funding; Acerta: Research Funding; Janssen: Consultancy, Research Funding; AstraZeneca: Research Funding; Pharmacyclics: Consultancy; Beigene: Research Funding; Verastem: Research Funding; Genmab: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Karmali:AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Takeda: Research Funding; BeiGene: Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau. Naik:Celgene: Other: advisory board; Sanofi: Other: advisory board. Smith:Janssen: Consultancy; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; BMS: Consultancy; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding. Rubenstein:Kymera: Research Funding. Kahl:BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy. Evens:Abbvie: Consultancy, Honoraria; Research To Practice: Honoraria, Speakers Bureau; MorphoSys: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria, Research Funding; Mylteni: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding. Martin:Kite: Consultancy; Morphosys: Consultancy; Regeneron: Consultancy; Incyte: Consultancy; Cellectar: Consultancy; Beigene: Consultancy; Bayer: Consultancy; I-MAB: Consultancy; Sandoz: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Teneobio: Consultancy; Celgene: Consultancy.