A Pilot Study of an Automated Voice Response System and Nursing Intervention to Monitor Adherence to Oral Chemotherapy Agents

This study was designed to develop and test a system to monitor adherence with non-hormonal oral chemotherapeutic agents using an automated voice response (AVR) system plus nursing intervention. Participants received the Symptom Management Toolkit then participated in an interview for symptom severity, satisfaction, and beliefs about oral agents. Patients received weekly AVR calls, which assessed adherence to oral agents and severity of 15 symptoms. Patients who reported adherence of \u3c 100% of prescribed oral agents or symptoms of 4 or greater (0-10 scale) for three consecutive weeks, were called by a nurse for assistance with symptom management and adherence to oral chemotherapy medications. Following the 8 weekly AVR calls, patients participated in a follow up interview and medical record review. Subjects were 30 oncology patients who were ambulatory and treated at two cancer centers in Midwest USA. The results indicate 23.3% non adherence rate to oral chemotherapy medications due to symptoms and forgetting to take the medication. An association between symptom management and adherence was found. Symptom severity and beliefs about medications were not significantly different between adherent and non adherent patients. This pilot study demonstrated the ability to accrue patients for a longitudinal trial and informed intervention design, while providing guidance for future interventions and research studies. This study was designed to develop and test a system to monitor adherence with nonhormonal oral chemotherapeutic agents using an automated voice response (AVR) system plus nursing intervention. Participants were patients diagnosed with solid tumor cancers, primarily breast, colon, and lung cancers, who received the Symptom Management Toolkit and participated in an interview for symptom severity, satisfaction, and beliefs about oral agents. Patients received weekly AVR calls, which assessed adherence to oral agents and severity of 15 symptoms. Patients who reported adherence of below 100% of the prescribed oral agents or symptoms of 4 or greater (0 Y 10 scale) for 3 consecutive weeks were called by a nurse for assistance with symptom management and adherence to oral chemotherapy medications. After the 8 weekly AVR calls, patients participated in a follow-up interview and medical record review. Participants were 30 oncology patients who were ambulatory and treated at 2 cancer centers in Midwest United States. The results indicate 23.3% nonadherence rate to oral chemotherapy medications due to symptoms and forgetting to take the medication. An association between symptom management and adherence was found. Symptom severity and beliefs about medications were not significantly different between adherent and nonadherent patients. This pilot study demonstrated the ability to accrue patients for a longitudinal trial and informed intervention design while providing guidance for future interventions and research studies

CD47 Expression Defines Efficacy of Rituximab with CHOP in Non-Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma Patients (DLBCL), but Not in GCB DLBCL

Addition of rituximab (R) to "CHOP" (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy improved outcome for diffuse large B-cell lymphoma (DLBCL) patients. Approximately 40% of patients who receive R-CHOP still succumb to disease due to intrinsic resistance or relapse. A potential negative regulator of DLBCL treatment outcome is the CD47 "don't eat me" immune checkpoint. To delineate the impact of CD47, we used a clinically and molecularly well-annotated cohort of 939 DLBCL patients, comprising both germinal center B-cell (GCB) and non-GCB DLBCL subtypes, treated with either CHOP or R-CHOP. High (above median) CD47 mRNA expression correlated with a detrimental effect on overall survival (OS) when DLBCL patients received R-CHOP therapy (P = 0.001), but not CHOP therapy (P = 0.645). Accordingly, patients with low CD47 expression benefited most from the addition of rituximab to CHOP [HR, 0.32; confidence interval (CI), 0.21-0.50; P <0.001]. This negative impact of high CD47 expression on OS after R-CHOP treatment was only evident in cancers of non-GCB origin (HR, 2.09; CI, 1.26-3.47; P = 0.004) and not in the GCB subtype (HR, 1.16; CI, 0.68-1.99; P = 0.58). This differential impact of CD47 in non-GCB and GCB was confirmed in vitro, as macrophage-mediated phagocytosis stimulated by rituximab was augmented by CD47-blocking antibody only in non-GCB cell lines. Thus, high expression of CD47 mRNA limited the benefit of addition of rituximab to CHOP in non-GCB patients, and CD47-blockade only augmented rituximab-mediated phagocytosis in non-GCB cell lines. Patients with non-GCB DLBCL may benefit from CD47-targeted therapy in addition to rituximab

Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis

CD47 is a prominent new target in cancer immunotherapy, with antagonistic antibodies currently being evaluated in clinical trials. For effective evaluation of this strategy it is crucial to identify which patients are suited for CD47-targeted therapy. In this respect, expression of the pro-phagocytic signal SLAMF7 on both macrophages and cancer cells was recently reported to be a requisite for CD47 antibody-mediated phagocytosis. Here, we demonstrate that in fact SLAMF7 expression on cancer cells is not required and does not impact on CD47 antibody therapy. Moreover, SLAMF7 also does not impact on phagocytosis induction by CD20 antibody rituximab nor associates with overall survival of Diffuse Large B-Cell Lymphoma patients. In contrast, expression of CD47 negatively impacts on overall and progression free survival. In conclusion, cancer cell expression of SLAMF7 is not required for phagocytosis and, in contrast to CD47 expression, should not be used as selection criterion for CD47-targeted therapy

Does cancer cell-expressed SLAMF7 impact on CD47-mediated phagocytosis?

Innate immune checkpoint CD47 has emerged as a prominent target for cancer immunotherapy and defining biomarkers predictive of response will be a crucial step towards clinical implementation. Hereto, we investigated the importance of a previously reported requisite for SLAM family member 7(SLAMF7) expression on cancer cell phagocytosis for effective CD47 antibody therapy