De novo CD5+ diffuse large B-cell lymphomas (DLBCL) are a distinct subgroup of DLBCL with poor prognosis. However the role of rituximab-containing therapy and salvage stem cell transplantation in this patients’ population remain to be defined. We retrospectively reviewed clinical features and outcomes of 102 patients with de novo CD5+ DLBCL treated with rituximab-containing therapy at 9 different institutions. By Hans’ criteria, 64 patients had activated B-cell (ABC) subtype, 24 germinal center B-cell (GCB) subtype, and 14 were not evaluated. No patients had a myc translocation. Eighty-three patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), 7 with rituximab, etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone (R-EPOCH) and 6 with R-CHOP with methotrexate, 3 g/m2. The overall response rate to frontline therapy was 85%. The 3-year progression free survival (PFS) and overall survival (OS) for all patients were 40% and 65%, respectively. The 3-year PFS for ABC- and GCB-subtypes was 34% and 45%, respectively. The 3-year OS for ABC- and GCB-subtypes was 62% and 67%, respectively. The median time to second treatment failure was 3 months and 1 month for ABC- and GCB-subtypes, respectively. Twenty of 28 (71%) transplanted patients with autologous, allogeneic, or both, relapsed. This study confirms the poor prognosis of de novo CD5+ DLBCL in a large multi-center cohort despite initial rituximab-containing chemotherapy and suggests that stem cell transplantation fails to salvage the majority of these patients. Approaches to prevent recurrence and/or novel therapies for relapsed disease are needed for this subgroup of DLBCL patients.

Background Although classical Hodgkin lymphoma (cHL) is highly curable, 20%–30% of patients will not be cured with conventional treatments. The programmed death‐1 (PD‐1) inhibitors (PD‐1i) nivolumab and pembrolizumab have been Food and Drug Administration‐approved for relapsed/refractory (R/R) cHL. There is limited data on the real‐world experience with PD‐1i in cHL and it is unknown whether fewer selected patients treated with PD‐1i derive benefits similar to those observed in published trials. Materials and Methods We performed a multicenter, retrospective analysis of R/R cHL patients treated with PD‐1i in the nontrial setting. The primary objective was to describe progression‐free survival (PFS) and overall survival (OS) in this population. Secondary objectives were to characterize response rates, toxicities, discontinuation patterns, and post‐PD‐1i therapies. Results The study included 53 patients from nine U.S. centers. Overall response rate (ORR), complete response (CR), and partial response (PR) to PD‐1i were 68%, 45%, and 23%, respectively. Twelve‐month OS and PFS were 89% and 75%, respectively; median PFS was 29 months. Ninety‐six percent of patients with CR continue to respond at a median follow‐up of 20 months. Toxicities were similar to those previously described. Seventy percent of patients treated with systemic therapy after PD‐1i demonstrated objective responses. Conclusion To our knowledge, this analysis is the first describing real‐world experience with PD‐1i in cHL patients in the U.S. Here, we demonstrate similar response rates compared to prior studies. The toxicity profile of PD‐1i was similar to that seen in previous studies; we further describe toxicity patterns in those with prior autoimmune disease or allogeneic transplant. Post‐PD‐1i systemic therapies appear active. These results support the effectiveness and tolerability of PD‐1i therapy in R/R cHL in a real‐world setting. Implications for Practice Two PD‐1 inhibitors have recently been approved for patients with relapsed/refractory classical Hodgkin lymphoma based on results from nonrandomized clinical trials. However, to date, there have been no studies evaluating the effectiveness and toxicity profile of these drugs in the real‐world setting in the U.S. The present study demonstrates that patients treated in a real‐world context experience similar rates of overall effectiveness compared with published clinical trials. Patients who discontinue PD‐1 inhibitors may experience clinical responses to subsequent treatment with systemic chemotherapy or targeted therapy. This study provides clinicians with further insight into the effectiveness and tolerability of PD‐1 inhibitors and suggests that when patients progress while on these drugs, conventional systemic chemotherapy may be an effective treatment option.

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Subtypes of diffuse large B-cell lymphoma (DLBCL) that have inferior outcomes after front-line therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) have been identified. While it is agreed that R-CHOP is probably not adequate in these patients, there is no standard treatment approach for patients with DLBCL with high-risk features. We present results of a retrospective cohort study of high-risk DLBCL (defined as having at least one unfavorable risk factor: non-germinal center [GC] subtype by immunohistochemistry [IHC], Ki-67 ≥ 80%, high International Prognostic Index [IPI], c-MYC rearrangement) treated with R-HCVAD/R-MTX-AraC (rituximab, cyclophosphamide-fractionated, vincristine, doxorubicin and dexamethasone alternating with rituximab, methotrexate and cytarabine; R-HCVAD) as front-line therapy. With a median follow-up of 25.3 months, the 3-year PFS and OS estimates are 79% (95% confidence interval [CI], 65-88%) and 76% (95% CI, 61-86%), respectively, which are higher than those for historical comparisons with R-CHOP data for high-risk patients. These data are in accord with other recent reports of dose-intense front-line therapy of high-risk DLBCL. This analysis represents the largest reported cohort of patients with DLBCL treated with R-HCVAD. These data suggest that R-HCVAD can overcome traditional poor risk features such as high IPI, high Ki-67 and non-GC IHC pattern. Future work will focus on identifying molecular markers for failure in patients with DLBCL treated with dose-intensive regimens.

Cancer of unknown primary is defined as a metastatic disease present in the absence of an identifiable primary site of origin. Squamous cell carcinoma (SCC) of unknown primary is a relatively uncommon subtype that usually involves metastases to the cervical or inguinal lymph nodes. We present a rare case of SCC of unknown primary metastasizing to the gallbladder fossa and creating a duodenal fistula. This case highlights the rarity of SCCs in the gallbladder region and the risks posed by chemotherapy in patients with gastrointestinal fistulas.