(2020). Pembrolizumab monotherapy in patients with primary refractory classical hodgkin lymphoma who relapsed after salvage autologous stem cell transplantation and/or brentuximab vedotin therapy: KEYNOTE-087 subgroup analysis. Leukemia & Lymphoma. Ahead of Print.

In classical Hodgkin Lymphoma (cHL), immunoediting via protein signaling is key to evading tumor surveillance. We aimed to identify immune-related proteins that distinguish diagnostic cHL tissues (=diagnostic tumor lysates, n = 27) from control tissues (reactive lymph node lysates, n = 30). Further, we correlated our findings with the proteome plasma profile between cHL patients (n = 26) and healthy controls (n = 27). We used the proximity extension assay (PEA) with the OlinkTM multiplex Immuno-Oncology panel, consisting of 92 proteins. Univariate, multivariate-adjusted analysis and Benjamini–Hochberg’s false discovery testing (=Padj) were performed to detect significant discrepancies. Proteins distinguishing cHL cases from controls were more numerous in plasma (30 proteins) than tissue (17 proteins), all Padj < 0.05. Eight of the identified proteins in cHL tissue (PD-L1, IL-6, CCL17, CCL3, IL-13, MMP12, TNFRS4, and LAG3) were elevated in both cHL tissues and cHL plasma compared with control samples. Six proteins distinguishing cHL tissues from controls tissues were significantly correlated to PD-L1 expression in cHL tissue (IL-6, MCP-2, CCL3, CCL4, GZMB, and IFN-gamma, all p ≤0.05). In conclusion, this study introduces a distinguishing proteomic profile in cHL tissue and potential immune-related markers of pathophysiological relevance.

Current research seeks to identify subgroups of non-Hodgkin lymphoma (NHL) patients responsive to PD-1 blocking agents. Whether patients with pre-existing rheumatic diseases might constitute such a subgroup is unknown. We determined intratumoral expression of PD-1 and its ligands in lymphoma patients with pre-existing rheumatic diseases. We included 215 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or Sjögren’s syndrome with subsequent lymphoma and 74 diffuse large B-cell lymphoma (DLBCL) controls without rheumatic disease. PD-1 and PD-ligand immunohistochemical markers were applied on tumor tissue microarrays. The number of PD-1+ tumor infiltrating leukocytes (TILs) and proportions of PD-L1+ and PD-L2+ tumor cells and TILs were calculated and correlated with clinical data. Expression of PD-L1 in tumor cells and TILs was highest in classical Hodgkin lymphoma and DLBCL. In DLBCLs, expression of PD-1 in TILs and PD-L1 in tumor cells was similar in RA, SLE and controls. In RA-DLBCL, high expression of PD-L1 in tumor cells was significantly more common in patients with the most severe RA disease and was associated with inferior overall survival in multivariable analysis.

No universal gold standard chemotherapy exists for the treatment of older (≥60 years) patients with classical Hodgkin lymphoma (cHL). To evaluate the current curative treatment strategies used in the Nordic countries, we collected data from patients diagnosed in Sweden, Denmark and Norway during the years 2000 to 2021. We included 1569 patients: 704 (45%) Swedish, 671 (43%) Danish and 194 (12%) Norwegian. Of these, 671 (43%) received doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), 123 (8%) received doxorubicin, vinblastine, dacarbazine (AVD), 465 (31%) received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and 212 (13%) received other chemotherapy (single agent or combination). Eighty-two patients (5%) lacked information on first line regimen. In multivariable analyses of overall survival (OS), treatment with AVD was associated with improved survival compared to ABVD, whereas there was a trend toward inferior survival among patients receiving CHOP or other regimens. For progression-free survival (PFS), multivariable analysis likewise demonstrated significantly improved outcome with AVD relative to ABVD, while outcomes for the CHOP group were comparable to ABVD. Outcome for patients receiving other regimens tended to be poorer. Collectively, outcome for AVD with respect to both OS and PFS was at least equal to ABVD and often superior to CHOP. By omitting bleomycin, treatment-related toxicity is known to be reduced in AVD compared to ABVD. Based on our findings, AVD is a preferable chemotherapy option in older cHL patients and should rightly be considered as backbone in treatment with novel drugs.

Background and PurposeProton radiotherapy may spare normal tissue compared with photon radiotherapy due to its finite range. This effect can be further enhanced by deep inspiration breath-hold (DIBH), which displaces the heart away from the high-dose volume and reduces breathing-related uncertainties. However, the mediastinal position in DIBH varies, even though the breathing measure, in terms of vertical displacement of the thorax (thoracic point, TP), is within tolerance (gating window). The aim of this study is to assess whether vertical displacements of an abdominal point (AP) can explain mediastinal deviation in DIBH (ΔM). Materials and MethodsFor 14 mediastinal lymphoma patients treated with proton radiotherapy in DIBH, the correlation between the surface surrogates (TP and AP) and mediastinal displacement was assessed using weekly control CTs in DIBH and corresponding respiratory motion surrogate data acquired by a surface scanning system. ResultsIn 7 of the 75 CTs (9 %), the mediastinum deviated more than 5 mm from the planned position, even though the TPs were within the 3 mm tolerance, and in 4 CTs (5 %) the mediastinum deviated more than 10 mm. The maximum deviation was 24 mm. A linear correlation with slope 0.6 (R2 = 0.6, p < 0.001, α = 0.05) was found between the AP position and mediastinal displacement. ConclusionsVertical abdominal displacements showed a statistically significant correlation with mediastinal displacements. Controlling TP and AP levels can potentially reduce the positional variability of the mediastinum in DIBH.

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