Alhaj Moustafa, Muhamad

Objectives: Anaplastic thyroid cancer (ATC) is a rare and aggressive type of thyroid malignancy with a very poor prognosis and outcome despite therapy. The rarity of this disease and the poor functional status of ATC patients limit the ability to conduct clinical trials, thus there is a lack of large, controlled trials to guide treatment and evaluate the benefit of combined modality therapy. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with ATC at age 18 or older between 2004 and 2018. After excluding patients with unknown number of treatment modalities, Charlson-Deyo score—a weighted summary of 17 chronic disease categories where higher scores denote greater baseline comorbidity burden—of 3 or more and patients lost for follow-up, we split the cohort into 3 groups according to the number of treatment modalities they received. Treatment modalities included surgery, radiation, and systemic therapy. Then, we evaluated the overall survival (OS) between the 3 groups. We studied the OS using Kaplan-Meier estimates and multivariate Cox regression analyses to evaluate factors associated with OS. In addition, propensity score matching (accounting for age, sex, race, Charlson-Deyo score, and clinical M stage) was used for more robust results. Results: A total of 3460 patients with ATC were included in the analysis, of which 1472 (42.5%) either received one type of therapy or did not receive any therapy (group 1), 1092 (31.6%) received bimodal therapy (group 2), and 896 (25.9%) received trimodal therapy (group 3). We found that group 3 had better OS compared with group 1 and group 2 (median OS 9.1 vs. 1.7 and 4.9 mo, respectively, with P <0.001 for all comparisons). Propensity score matching yielded 896 patients in each group. We found that group 3 had better OS compared with group 1 and group 2 (median OS 9.1 vs. 1.9 and 5.2 mo, respectively, with P <0.001 for all comparisons). Same trend was found in subgroup analysis when we split the cohort according to the metastatic status; in M0 group (median OS was 10.4 vs. 1.9 and 6.1 mo, respectively, with P <0.001 for all), in M1 group (median OS was 5.9 vs. 1.4 and 3.7 mo, respectively, with P <0.001 for all). Modality-specific analyses further demonstrated that surgery, radiation, and systemic therapy each independently prolonged OS in both M0 and M1 cohorts (all P <0.001). These individual benefits explain the additive advantage of trimodal therapy and underscore that offering at least one evidence-based modality is preferable when comprehensive treatment is infeasible. On multivariate analysis, group 1 and group 2 were associated with worse OS compared with trimodal treatment (HR: 2.721; 95% CI: 2.466-3.002 and HR: 1.434; 95% CI: 1.299-1.582, P <0.001 for all). Conclusions: Patients with ATC who were treated with intensive trimodal therapy had statistically significant improvement in OS compared with patients who received less intense therapy. This survival benefit was observed in both metastatic and nonmetastatic groups. Although we acknowledge the limitations of this retrospective analysis, our results showed the critical role of an intensive therapy approach in this aggressive malignancy.

Daratumumab is an anti-CD38 mAb, used frequently in combination with lenalidomide and pomalidomide. No studies compared daratumumab plus lenalidomide and dexamethasone (DRd) to daratumumab plus pomalidomide and dexamethasone (DPd) in lenalidomide-exposed multiple myeloma. We identified 504 consecutive multiple myeloma patients who received daratumumab at Mayo Clinic between January 2015 and April 2019. We excluded patients who received daratumumab in the first line, received more than four lines of therapy prior to daratumumab use, did not receive lenalidomide prior to daratumumab, or had an unknown status of lenalidomide exposure, and patients who received daratumumab combinations other than DRd or DPd. We examined the impact of using DRd compared to DPd on progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory multiple myeloma. Out of 504 patients, 162 received DRd or DPd and were included; 67 were lenalidomide-exposed and 95 were lenalidomide-refractory. DRd was used in 76 (47%) and DPd in 86 (53%) patients. In lenalidomide-exposed multiple myeloma, there was no difference in median PFS; 34.2 months [95% confidence interval (CI), 22.8–44.6] for DRd compared to 25.2 months (95% CI, 4.9–35.3) for DPd, P = 0.2. In lenalidomide-refractory multiple myeloma, there was no difference in median PFS; 18.6 months (95% CI, 13–32) for DRd compared to 9 months (95% CI, 5.2–14.6) for DPd, P = 0.09. No difference in median OS was observed in DRd compared to DPd. Our study shows combining daratumumab with lenalidomide in patients with prior lenalidomide use is a viable and effective treatment option.

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.

SummaryRuxolitinib for steroid‐refractory acute graft‐versus‐host disease (SR‐aGVHD) results in resistance or intolerance in 1/5 of patients. Outcomes of such patients are undefined. We identified these patients in a multicentre review and reported outcomes. Ruxolitinib‐resistant aGVHD was identified in 48/307 patients. Among patients receiving additional therapy, the overall response rate to next therapy was 36%. Median survival was 21 days. Ruxolitinib intolerance led to treatment discontinuation in 16/307 patients. Ten intolerant patients received additional therapy with 50% experiencing continued improvement of aGVHD. Median survival was 50 days in these patients. These data serve as a baseline for future SR‐aGVHD studies.

AbstractThis case illustrates an unusual presentation of paraneoplastic myositis in stage IV follicular lymphoma managed with high‐dose steroids, a previously unreported entity in the literature.

AbstractPrimary appendiceal lymphomas (PAL) are a type of primary gastrointestinal non‐Hodgkin lymphoma (PGINHL) with an incidence of <1%. There is considerable discordance with regard to the optimal management of PGINHL. We describe two cases of PAL, perform a literature review, and discuss the available evidence for optimal treatment.