Mogamulizumab versus investigator's choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma.

Mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, has been approved in Japan for the treatment of C-C chemokine receptor 4-positive adult T-cell leukemia/lymphoma (ATL). This phase II study evaluated efficacy and safety of mogamulizumab in ATL patients with acute, lymphoma, and chronic subtypes with relapsed/refractory, aggressive disease in the US, Europe, and Latin America. With stratification by subtype, patients were randomized 2:1 to intravenous mogamulizumab 1.0 mg/kg once weekly for 4 weeks and biweekly thereafter (n=47) or investigator's choice of chemotherapy (n=24). The primary end point was confirmed overall response rate (cORR) confirmed on a subsequent assessment at 8 weeks by blinded independent review. ORR was 11% (95%CI: 4-23%) and 0% (95%CI: 0-14%) in the mogamulizumab and chemotherapy arms, respectively. Best response was 28% and 8% in the respective arms. The observed hazard ratio for progression-free survival was 0.71 (95%CI: 0.41-1.21) and, after post hoc adjustment for performance status imbalance, 0.57 (95%CI: 0.337-0.983). The most frequent treatment-related adverse (grade ≥3) events with mogamulizumab were infusion-related reaction and thrombocytopenia (each 9%). Relapsed/refractory ATL is an aggressive, poor prognosis disease with a high unmet need. Investigator's choice chemotherapy did not result in tumor response in this trial; however, mogamulizumab treatment resulted in 11% cORR, with a tolerable safety profile.

Thrombolytic therapy is effective in paroxysmal nocturnal hemoglobinuria: a series of nine patients and a review of the literature.

BACKGROUND: Thrombosis is the major risk factor for death in patients with paroxysmal nocturnal hemoglobinuria. Previous case reports indicate that venous thrombosis in patients with paroxysmal nocturnal hemoglobinuria is amenable to thrombolysis. DESIGN AND METHODS: We reviewed the outcome of thrombolytic therapy for patients with paroxysmal nocturnal hemoglobinuria who had thromboses refractory to anticoagulation at our institutions. RESULTS: In this study of 41 patients who had at least one thrombotic event, we confirmed a very high incidence of recurrence despite anticoagulation. Nine patients with thrombosis were regarded as eligible for administration of intravenous tissue plasminogen activator, which was effective in reversing thrombi in all of 15 occasions in which it was given. Serious hemorrhagic complications developed in three cases. At last follow-up visit, of the nine patients treated, three had died, and six were in very good to excellent condition in terms of clinical outcome and radiological findings. The only patient in whom thrombolysis may have contributed to a fatal outcome also had complications of "heparin induced thrombocytopenia with thrombosis", which we diagnosed in three additional patients. In our review of the literature, nine out of 15 patients treated with thrombolysis have had a good outcome. CONCLUSIONS: Although it is associated with a significant but manageable risk of bleeding, systemic thrombolysis is a highly effective treatment for reversing venous thromboses in patients with paroxysmal nocturnal hemoglobinuria.

Conducting Goals-of-Care Discussions Takes Less Time Than Imagined.

PURPOSE: To describe the length of encounter during visits where goals-of-care (GoC) discussions were expected to take place. METHODS: Oncologists from community, academic, municipal, and rural hospitals were randomly assigned to receive a coaching model of communication skills to facilitate GoC discussions with patients with newly diagnosed advanced solid-tumor cancer with a prognosis of < 2 years. Patients were surveyed after the first restaging visit regarding the quality of the GoC discussion on a scale of 0-10 (0 = worst; 10 = best), with ≥ 8 indicating a high-quality GoC discussion. Visits were audiotaped, and total encounter time was measured. RESULTS: The median face-to-face time oncologists spent during a GoC discussion was 15 minutes (range, 10-20 minutes). Among the different hospital types, there was no significant difference in encounter time. There was no difference in the length of the encounter whether a high-quality GoC discussion took place or not (15 v 14 minutes; P = .9). If there was imaging evidence of cancer progression, the median encounter time was 18 minutes compared with 13 minutes for no progression (P = .03). In a multivariate model, oncologist productivity, patient age, and Medicare coverage affected duration of the encounter. CONCLUSION: Oncologists can complete high-quality GoC discussions in 15 minutes. These data refute the common misperception that discussing such matters with patients with advanced cancer requires significant time.

Clinical Characteristics and Outcomes of Caribbean Patients With Adult T-Cell Lymphoma/Leukemia at Two Affiliated New York City Hospitals.

PURPOSE: Adult T-cell lymphoma/leukemia (ATL) is a rare and aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus-1 infection, which occurs in areas of high prevalence, predominantly in Japan and the Caribbean basin. Most ATL literature is derived from Japan and little is published about Caribbean patients. We describe the clinicopathologic characteristics and treatment outcomes of our Caribbean patients who have ATL at the State University of New York Downstate Medical Center and Kings County Hospital. PATIENTS AND METHODS: We conducted a retrospective analysis of our patients with ATL who were diagnosed between 2005 and 2017. Medical records were reviewed for clinicopathologic data and treatment outcomes. The final analysis included acute and lymphomatous subtypes only. For the univariable analysis, outcomes were calculated by using a log-rank test, and survival curves were estimated by the Kaplan-Meier method. RESULTS: We identified 63 patients with acute (55%) and lymphomatous (45%) subtypes, 95% of whom had Ann Arbor stage III to IV disease. The median age was 54 years, and the study population was predominantly female (65%). Most patients (82%) received first-line etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone (EPOCH) or cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) chemotherapy (10%) with an overall response rate of 46%. The median overall survival was 5.5 months, and the median progression-free survival was 4 months. Incidence of atypical immunophenotype (32%) was higher than previously reported in the Japanese literature and was associated with worse survival (P = .04). Abnormal cytogenetics correlated with shorter progression-free survival (P < .05). CONCLUSION: We describe here the clinicopathologic characteristics and treatment outcomes of our Caribbean patients with aggressive ATL, which is largely chemotherapy resistant, and the challenges of treating a population with unmet medical needs.

Impact of High-Quality Goals-of-Care Discussions on Oncologist Productivity.

PURPOSE: To study factors that have an impact on the conduct of high-quality goals of care (GoC) discussions and productivity of oncologists among four different practice settings in patients with advanced cancer. METHODS: Solid-tumor oncologists from community, academic, municipal, and rural hospitals were randomly assigned to receive a coaching model of communication skills to help them facilitate a GoC discussion with newly diagnosed patients with advanced cancer who had a less-than-2-year prognosis. Patients were surveyed after the first restaging visit regarding the quality of the GoC discussion on a scale of 0 to 10 (0, worst; 10, best) with a score of 8 or better indicating a high-quality GoC discussion. Productivity was measured by work revenue value units (wRVUs) per hour for the day each oncologist saw the study patient after imaging. RESULTS: The four sites differed significantly in the socioeconomic patient populations they served and in the characteristics of the oncologists who cared for the patients. Overall median productivity across the four sites was 3.6 wRVU/hour, with the highest observed in the community hospital (4.3 wRVU/hour) and the lowest in the rural setting (2.9 wRVU/hour; P < .001). There was no significant difference in productivity observed when high-quality GOC discussion occurred versus when it did not (3.6 v 3.7 wRVU/hour; P = .86). CONCLUSION: Despite differences in patient populations and oncologists' characteristics between the four practice settings, the conduct of high-quality GoC discussions did not affect productivity.

Effects of a Communication Intervention Randomized Controlled Trial to Enable Goals-of-Care Discussions.

PURPOSE: Patients with advanced cancer often have a poor understanding of cancer incurability, which correlates with more aggressive treatment near the end of life (EOL). We sought to determine whether training oncologists to elicit patient values for goals-of-care (GoC) discussions will increase and improve these discussions. We explored its impact on use of aggressive care at EOL. METHODS: We enrolled and used block randomization to assign 92% of solid tumor oncologists to 2-hour communication skills training and four coaching sessions. We surveyed 265 patient with newly diagnosed advanced cancer with < 2-year life expectancy at baseline and 6 months. We assessed prevalence and quality of GoC communication, change in communication skills, and use of aggressive care in the last month of life. RESULTS: Intervention (INT) oncologists' (n = 11) skill to elicit patient values increased (27%-55%), while usual care (UC) oncologists' (n = 11) skill did not (9%-0%; P = .01). Forty-eight percent (n = 74) INT v 51% (n = 56) UC patients reported a GoC discussion (P = .61). There was no difference in the prevalence or quality of GoC communication between groups (global odds ratio, 0.84; 95% CI, 0.57 to 1.23). Within 6 months, there was no difference in deaths (18 INT v 16 UC; P = .51), mean hospitalizations (0.47 INT v 0.42 UC; P = .63), intensive care unit admissions (5% INT v 9% UC; P = .65), or chemotherapy (26% INT v 16% UC; P = .39). CONCLUSION: Use of a coaching model focused on teaching oncologists to elicit patient values improved that skill but did not increase prevalence or quality of GoC discussions among patients with advanced cancer. There was no impact on high care utilization at EOL.

Cancer Health Impact Program (CHIP): Identifying Social and Demographic Associations of mHealth Access and Cancer Screening Behaviors Among Brooklyn, New York, Residents.

BACKGROUND: The Bedford-Stuyvesant (BS) and Bushwick (BW) communities of central Brooklyn, New York, are located within the 50-mile core radius of Memorial Sloan Kettering's main catchment area. Cancer is the second leading cause of death among the predominantly African American and Hispanic neighborhoods, with BS and BW having higher prostate cancer and colorectal mortality rates than New York City as a whole. There is significant opportunity to design cancer interventions that leverage the accessibility and acceptability of mobile health (mHealth) tools among the BS and BW communities. METHODS: The Cancer Health Impact Program (CHIP) is a collaborative that was formed for this purpose. Through CHIP, we used a tablet-based, Health Information National Trends (HINTS)-based multimodality survey to collect and analyze social and demographic patterns of prostate cancer and colorectal cancer screening, as well as mHealth access, among BS and BW residents. RESULTS: Among 783 participants, 77% reported having a smartphone, 40% reported access to a mobile health application, 17% reported blood stool kit testing, and 26% of men reported PSA test screening. Multivariable logistic regression models results demonstrated that participants who reported owning smartphones, but were unsure whether they had access to a health app, were also significantly more likely to report blood stool kit testing compared with participants without smartphones. In fully adjusted models, access to a health app was not significantly associated with PSA testing. Non-Hispanic white participants were 86% less likely to report blood stool kit testing when compared with non-Hispanic black participants [OR = 0.15; 95% confidence interval (CI) 0.02-0.49]. Participants with a prior history of cancer were three times more likely to report blood stool kit testing when compared with those without cancer history (OR = 3.18; 95% CI, 1.55-6.63). CONCLUSIONS: For blood stool kit testing, significant differences were observed by race/ethnicity, cancer history, age, and smartphone use; for PSA screening, only age was significant in fully adjusted models. IMPACT: Our results demonstrate that while access to smartphones and mobile health apps may be prevalent among minority communities, other social and demographic characteristics are more likely to influence screening behaviors.

Macrophage Inhibitory Factor-1 (MIF-1) controls the plasticity of multiple myeloma tumor cells.

Multiple Myeloma (MM) is the second most common hematological malignancy with a median survival of 5-10 years. While current treatments initially cause remission, relapse almost always occurs, leading to the hypothesis that a chemotherapy-resistant cancer stem cell (CSC) remains dormant, and undergoes self-renewal and differentiation to reestablish disease. Our finding is that the mature cancer cell (CD138+, rapidly proliferating and chemosensitive) has developmental plasticity; namely, the ability to dedifferentiate back into its own chemoresistant CSC progenitor, the CD138-, quiescent pre-plasma cell. We observe multiple cycles of differentiation and dedifferentiation in the absence of niche or supportive accessory cells, suggesting that soluble cytokines secreted by the MM cells themselves are responsible for this bidirectional interconversion and that stemness and chemoresistance are dynamic characteristics that can be acquired or lost and thus may be targetable. By examining cytokine secretion of CD138- and CD138+ RPMI-8226 cells, we identified that concomitant with interconversion, Macrophage Migration Inhibitory Factor (MIF-1) is secreted. The addition of a small molecule MIF-1 inhibitor (4-IPP) or MIF-1 neutralizing antibodies to CD138+ cells accelerated dedifferentiation back into the CD138- progenitor, while addition of recombinant MIF-1 drove cells towards CD138+ differentiation. A similar increase in the CD138- population is seen when MM tumor cells isolated from primary bone marrow aspirates are cultured in the presence of 4-IPP. As the CD138+ MM cell is chemosensitive, targeting MIF-1 and/or the pathways that it regulates could be a viable way to modulate stemness and chemosensitivity, which could in turn transform the treatment of MM.

Speaking Up: How Patient and Physician Voices Shaped a Trial to Improve Goals-of-Care Discussions.

BACKGROUND: Patients with advanced cancer benefit from early goals-of-care (GoC) conversations, but few facilitators are known. OBJECTIVE: We describe the process and outcomes of involving patient and physician stakeholders in the design and development of a trial, funded by the Patient-Centered Outcomes Research Institute (PCORI), to enhance oncologists' communication skills and their propensity to facilitate productive, meaningful GoC discussions with patients with advanced cancer. METHODS: We recruited oncologists, palliative care physicians, and patient stakeholders to participate in proposal development, intervention design and modification, identification of outcome measures, and refinement of study tools. Formats for exchange included 1:1 structured interviews, workshops, and stakeholder meetings. RESULTS: Patient and physician voices helped craft and implement a study of an intervention to enhance oncologists' ability to facilitate GoC discussions with patients with advanced cancer. Physician inputs guided the creation of an oncologist and palliative care physician "joint visit" intervention at a turning point in disease management. Patient inputs impacted on the language used, outcome measures assessed, and approaches used to introduce patients to the intervention visit. CONCLUSIONS: Stakeholder input informed the development of a novel intervention that physicians seemed to find both valuable and in sync with their needs and their practice schedules. Where communication about difficult subjects and shared decision making are involved, including multiple stakeholder groups in study design, implementation, and outcomes measurement may have far-reaching effects.