Faculty Bibliography

BACKGROUND:Data are sparse on treatment of chronic hepatitis C virus (HCV) in cancer patients. We evaluated the efficacy and safety of sofosbuvir-based therapy (SOFBT) in cancer patients. METHODS:Patients treated with SOFBT at our center during 2014-2017 were included in a prospective observational study. Efficacy [sustained virologic response at 12 weeks after the end of treatment (SVR12)], cancer-related outcomes and adverse events (AEs) were assessed. RESULTS:We included 153 patients. Most were men (109; 71%), white (92; 60%), non-cirrhotic (105; 69%), and with HCV genotype 1 (110; 72%). The most common cancers were hepatocellular carcinoma (HCC) (27; 18%) and multiple myeloma (14; 9%). The overall SVR12 rate was 91% (128/141). SVR12 was 100% in patients treated with ledipasvir/sofosbuvir for 8 weeks. Of the 32 patients initially excluded from cancer clinical trials because of HCV, 27 (84%) were granted cancer therapy access after starting SOFBT. Six patients with indolent non-Hodgkin's lymphoma (NHL) received SOFBT without cancer treatment. Two achieved complete remission, one had partial remission, and two had stable cancer. Within 6 months after SOFBT, 5% (6/121) of patients in remission or with stable cancer, had progression or recurrence (two with HCC and one each with esophageal cancer, cholangiocarcinoma, NHL, and tonsillar cancer). No de novo HCCs occurred. AEs were most commonly grade 1-2 (90%). CONCLUSIONS:SOFBT in HCV-infected cancer patients is effective and safe, may permit access to investigational cancer therapy expanding treatment options, may induce remission of NHL, and may be used for 8 weeks.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive hematologic malignancy derived from precursors of dendritic cells and involves most frequently the skin, bone marrow and lymph nodes. Diagnosis depends upon identification of specific tumor markers including CD4, CD56 and CD123. Historically, the median survival has been less than 2 years in most reported series. While for many years, conventional chemotherapy followed by stem cell transplantation was the standard of care, recently tagraxofusp, a cytotoxin directed against CD123, received United States Food and Drug Administration approval specifically for patients with BPDCN. In this review, we will discuss the markers used for diagnosis of BPDCN and focus on the new targeted treatments available. Specifically in BPDCN, tagraxofusp was highly effective with a safety profile found to be acceptable overall, with the noted occurrence of capillary leak syndrome. Future directions in therapy approaches for patients with BPDCN will include the development of other CD123-targeted agents, agents targeting beyond CD123 and investigation of rational combination approaches of CD123-directed therapy with other therapies.

There is a paucity of data regarding mixed mold pulmonary infections (MMPIs) in patients with haematological malignancies with or without haematopoietic stem cell transplantation (HSCT). We retrospectively studied 27 such patients (2005-2015) and compared them to patients with invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus. Factors associated with the diagnosis of MMPIs were significant corticosteroid use [20 (74%) vs 6 (22%), P < 0.001], sputum as the source specimen [13 (48%) vs 3 (11%), P = 0.003], younger age (median age: 58 vs 66 years, P = 0.006), and male sex [22 (81%) vs 13 (48%), P = 0.01]. Haematological cancers other than acute myeloid leukaemia (AML)/myelodysplastic syndromes (MDS) were less common in MMPIs than in IPA patients [AML/MDS: 6 (22%) vs 14 (52%), P = 0.04]. Only significant corticosteroid use [95% CI (2.7-42.7), P < 0.001], and sputum as the source specimen [95% (1.6-41.6), P = 0.012] were statistically significant as independently associated with increased risk of MMPIs diagnosis in multivariate analysis. Total mortality rate at day 42 postdiagnosis was comparable in both groups.

BACKGROUND:Although an association between hepatitis C virus (HCV) infection and oropharyngeal cancers (OPCs) has been reported, to the authors' knowledge the clinical significance of this epidemiological finding remains unknown. Therefore, the authors analyzed the oncologic outcomes of HCV-infected patients with OPCs. METHODS:In this retrospective cohort study, all patients with OPCs who were seen at The University of Texas MD Anderson Cancer Center between January 2004 and December 2015 were reviewed. HCV infection was defined as detectable HCV RNA in the serum. Five-year overall survival and progression-free survival rates were compared between patients infected with HCV and those not infected. RESULTS:A total of 161 patients were examined. The majority of the patients were white (141 patients; 88%) and male (132 patients; 82%) and had TNM stage III or IV disease (147 patients; 91%). The OPC involved the tonsils (83 patients; 52%), base of the tongue (67patients; 42%), or the soft palate (11 patients; 7%). The median follow-up after an OPC diagnosis was 3 years (range, 1-13 years). HCV-infected patients (25 patients) and HCV-uninfected patients (136 patients) were comparable with regard to smoking and alcohol status. In multivariate analysis, HCV was associated with increased cancer-specific mortality (hazard ratio, 2.15; 95% confidence interval, 1.08-6.85 [P = .02]) and risk of OPC progression (hazard ratio, 5.42; 95% confidence interval, 2.64-11.14 [P = .0008]) independent of age and cirrhosis status. Antivirals were administered after the diagnosis of OPC in 8 of the 25 HCV-infected patients (32%). HCV-infected patients who received antivirals were found to have better 5-year overall survival (70% vs 12%; P = .005) and progression-free survival (72% vs 19%; P = .005) compared with patients who did not. CONCLUSIONS:The early detection of HCV is important in patients with OPC because this infection may affect their oncologic outcomes. Cancer 2018;124:960-5. © 2017 American Cancer Society.

Hepatitis C virus (HCV) causes a chronic but curable infection associated with the development of marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). Preliminary data have shown frequent transformation of indolent lymphoma to DLBCL in HCV-infected patients. To compare their clinicopathologic characteristics and oncologic outcomes, we reviewed the medical records and pathology reports of HCV-infected and uninfected patients with DLBCL that transformed from indolent lymphoma seen at The University of Texas MD Anderson Cancer Center (June 2004 to May 2015). To identify predictors of DLBCL relapse, patients with relapse after first-line chemotherapy were compared with those without it using univariate and logistic regression analyses. Compared with the uninfected patients (n = 63), HCV-infected patients (n = 21) were younger (median age =54 years [interquartile range= 49-62 years] vs. 62 years [53-66 years]; p = 0.01) and more often had advanced DLBCL (Ann Arbor stage 3-4; 95% vs. 76%; p = 0.05). Immunophenotypically, more HCV-infected than uninfected patients had CD10-negative B cells (76% vs. 43%; p = 0.008), CD5-positive B cells (39% vs. 7%; p = 0.004) and activated B-cell phenotypes (57% vs. 31%; p = 0.07). Comparison of the patients who had relapse after first-line chemotherapy (n = 42) and those who did not (n = 40) revealed that having CD5-positive B cells was the only factor associated with DLBCL relapse in multivariate analysis (odds ratio= 10.7; p = 0.02). HCV-infected patients with transformed DLBCL have unique clinicopathologic characteristics that make their lymphoma difficult to treat, potentially leading to unfavorable outcome. The impact of HCV eradication should be explored in such patients.

UNLABELLED:IU/mL over baseline and hepatitis flare as an increase in alanine aminotransferase to ≥3 times the upper limit of normal. One hundred patients were studied, 50 with hematologic malignancies and 50 with solid tumors. Reactivation occurred in 23 (23%) patients, including 18 (36%) patients with hematologic malignancies and 5 (10%) patients with solid tumors. In univariate analysis, patients with reactivation were more likely than those without reactivation to have prolonged lymphopenia (median, 95 versus 22 days; P = 0.01) and to have received rituximab (44% versus 9%; P < 0.0001), bendamustine (22% versus 0%; P < 0.001), high-dose steroids (57% versus 21%; P = 0.001), or purine analogs (22% versus 5%; P = 0.02). Rituximab (odds ratio = 9.52; P = 0.001), and high-dose steroids (odds ratio = 5.05; P = 0.01) retained significance in multivariable analysis. Of the 23 patients with reactivation, 10 (43%) had hepatitis flare. No patient with reactivation experienced liver failure or liver-related death within 36 weeks after initiation of cancer treatment. Fourteen patients with hepatitis flare, six of whom had reactivation, required discontinuation or dose reduction of cancer treatment. CONCLUSION:HCV reactivation occurred in 23% of HCV-infected patients receiving cancer treatment, and most had an unremarkable clinical course. However, reactivation can affect the cancer treatment plan. Our findings suggest that HCV infection should not contraindicate cancer therapy and infected patients should have access to multiple cancer treatments with close monitoring while receiving regimens associated with HCV reactivation. (Hepatology 2018;67:36-47).

BACKGROUND:Historically considered to have very poor outcome, there is paucity of recent data regarding invasive mold infections (IMIs) of the central nervous system (CNS) in patients with hematologic cancer (HC) or stem cell transplantation (SCT). METHODS:We reviewed the records of HC patients and/or SCT recipients who were diagnosed with CNS IMIs (EORTC/MSG criteria) at MD Anderson Cancer Center (1/1/2000-6/31/2016). Risk factors for survival at day (d) 42 post diagnosis were assessed. RESULTS:We identified 40 such patients (16 with proven infection). The incidence density was 3.8 cases/100000 patient days and mortality remained stable throughout the study period. Most patients had active HC and neutropenia at diagnosis (95% and 53% respectively). Of the 25 patients with a microbiological diagnosis, Aspergillus spp and Mucorales accounted for 85% of cases. CNS IMIs were deemed to be secondary to hematogenous spread in 31 (77%), mostly (90%) fungal pneumonia. CNS lesions typically presented as solitary ring-enhancing abscesses in MRI (26; 65%). Most patients (34; 85%) received lipid AMB and were treated with combination therapy (33; 83%); Mortality 42d was 48%. In univariate analysis, lack of surgical drainage (p = 0.01), absence of giant cells (p = 0.01) and granulomas (p = 0.03) were associated with increased 42d mortality. In multivariate analysis, co-infection was associated with increased (p = 0.005), while steroid tapering was associated with decreased mortality (p = 0.01). CONCLUSIONS:Although less lethal, improved outcome in these uncommon infections was related only to immune response in histopathology, steroid tapering and possibly surgical drainage. In a contemporary 16-year cohort of 40 patients with hematologic cancer and mold infections of Central Nervous System, 42-day mortality was 48%. Improved survival was related to immune response in histopathology, absence of co-infections, corticosteroid tapering and possibly surgical drainage.