Efficacy of gemcitabine in combination with nanoparticle albumin-bound paclitaxel in the treatment of recurrent ovarian cancer: A retrospective single institution review.

BACKGROUND: The objective of this study was to evaluate the efficacy of gemcitabine plus nab-paclitaxel in patients with recurrent ovarian cancer. METHODS: We performed a single institution retrospective review of patients with recurrent ovarian cancer who were treated with gemcitabine plus nab-paclitaxel from 2012 to 2018 at the Mayo Clinic in Florida. RESULTS: Twenty patients were identified and the median PFS for patients treated with gemcitabine plus nab-paclitaxel was 9 months (95% CI, 5.7-20.7). Overall, 17 of the 20 patients (85%) achieved a clinical benefit (complete response 5%, partial response 55%, or stable disease at 3 months 25%). For platinum-sensitive disease and platinum-resistant disease, the median OS were 38.7 months (95% CI, 5.8-63.1) and 31.2 months (95% CI, 12.8-51.8), respectively (p = 0.4306). CONCLUSION: This well-tolerated regimen shows promising activity in recurrent ovarian cancer and is a viable option for patients who are intolerant to paclitaxel or carboplatin because of allergic reactions.

Emerging therapeutic agents for advanced non-small cell lung cancer.

Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor prognosis and no known cure. Survival time is often short because of limited treatment options. Recent advances in targeted therapy and immunotherapy have changed the landscape for the treatment of advanced NSCLC. In the last 10 years, the US Food and Drug Administration (FDA) has approved more than 17 new medications for this devastating disease and more are coming. Molecular and immunogenic testing makes personalized medicine possible for patients with advanced NSCLC. The new medications provide promising efficacy and safety resulting in improved long-term survival for a significant number of patients. In this review, we summarize the recent advances in advanced/metastatic NSCLC therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to current standard drugs in the same class or are a completely new class of drugs with novel mechanisms of action. Advances are divided into (1) targeted agents, (2) antibody-drug conjugates, and (3) immunotherapies. Finally, we present a brief review of the emerging agents and ongoing clinical studies.

Survival Trends in Young Patients With Multiple Myeloma: A Focus on Racial-Ethnic Minorities.

INTRODUCTION: Outcomes in multiple myeloma (MM) have improved significantly over time. This is true overall for all patients as well as patient subgroups based on age and race/ethnicity. Despite this, disparities are noted in outcomes when looking at racial subgroups. MATERIALS AND METHODS: We performed an analysis from the population-based Surveillance, Epidemiology, and End Results (SEER) database to evaluate improvement in relative survival rates (RSRs) for young (≤ 40 years at the time of MM diagnosis) and older (> 40 years at the time of MM diagnosis) over time by race/ethnicity, specifically focusing on Hispanic patients with MM. Expected survival was estimated using the age- and gender-specific death rates from the United States population. RSR was provided as the ratio of the observed to expected survival at individual time points. Five-year and 10-year RSRs were calculated for patients based on treatments modalities available in various time periods. RESULTS: We identified a total of 89,451 patients with MM in SEER, of which 1460 patients formed the young patients with MM (≤ 40 years) cohort. Five- and 10-year RSR improved significantly over time for all patients and older patients (> 40 years) by race (all P < .001). Evaluating the younger patients, RSR improved significantly for non-Hispanic whites and non-Hispanic blacks, but not for Hispanics. This was true for the 5-year (P = .08) and 10-year (P = .13) RSRs. CONCLUSION: We report a lack of significant benefit in long-term outcomes for younger Hispanic patients with MM over time. This could be owing to multifactorial causes that need to be addressed to mitigate outcome disparities.

Monoclonal antibody utilization characteristics in patients with multiple myeloma.

This study analyzed 91 multiple myeloma patients who received two monoclonal antibodies, Daratumumab and Elotuzumab, over a year and report the adverse event profile, infusion practices and utilization of these drugs in the real world. All current reported data on monoclonal antibodies is from clinical trials, without any real-world experience. Patients from Mayo Clinic Florida or Arizona diagnosed with relapsed or refractory multiple myeloma who were treated with Daratumumab or Elotuzumab alone or in combination between 1 January 2016 and 31 December 2016 were included in the analysis. Daratumumab-treated patients (n = 78) were more heavily pre-treated than that in published clinical trials, whereas the elotuzumab patient (n = 13) profile was similar to that published before. Infusion time was on average 2 hours less than the prescribing guidelines and premedication use varied noticeably after the initial monoclonal antibody infusion, with an overall decrease over time. We noted higher than reported haematologic adverse events, especially neutropenia and fewer non-haematologic adverse events. 91.7% infusion-related reactions were observed during the first monoclonal antibody infusion, with a subsequent decrease. All infusion-related reactions were grade 2 or less, and none of the patients discontinued treatment due to infusion-related reactions. Baseline allergy profile or laboratory tests were not associated with the likelihood of developing monoclonal antibody-related infusion-related reactions. The real-world safety profile of monoclonal antibodies showed varying adverse event patterns than those reported in previous clinical trials. The infusion-related reaction patterns were similar to previous reports. Despite changes in premedication regimens safety was maintained in succeeding infusions. Such treatment utilization data is vital to broaden our knowledge of approved therapeutic agents and maximize their benefits for patients.

Impact of good and poor mobilizers on hematopoietic progenitor cell collection efficiency and product quality.

BACKGROUND: Mobilization regimen choice is a significant contributing factor for successful hematopoietic progenitor cell (HPC) collection by leukocytapheresis and reaching the target CD34+ cell dose. How mobilization regimen affects collection efficiency and the quality of products collected using the Spectra Optia apheresis instrument is not fully known. METHODS: We evaluated the impact of granulocyte-colony stimulating factor (GCSF) and GCSF/plerixafor mobilization regimens on CE and product composition. We studied 373 leukocytapheresis HPC collections for 147 autologous transplants from January 1, 2010 to December 31, 2014. Patients were categorized in two groups; good mobilizers, mobilized with GCSF only (GM) and poor mobilizers, mobilized with GCSF and Plerixafor (PM). RESULTS: Overall, compared with PM group, total nucleated cell (TNC) yield was significantly lower in GM group (P = <.001). In contrast, median percent mononuclear cell (MNC) collected from GM (86.5%) was significantly higher than products collected from PM group (79.5%; P < .001). Compared with GM group, CD34+ cell CE was about 10% lower in PM group (P < .008). In addition, daily CD34+ cell/Kg yield was significantly higher in GM (2.08 × 10/Kg) compared with PM group (1.64 x 10/Kg, P = .019). Overall, the median number of collections per patient was two for GM and three for PM (P = .004). CONCLUSION: Products collected from PM group contained higher TNC content relative to GM group but had lower MNC enrichment, CD34+ cell CE and daily CD34+ cell yield per Kg.

Myelodysplasia-related acute myeloid leukemia and acute promyelocytic leukemia: concomitant occurrence of two molecularly distinct diseases.

Concurrent presentation of acute promyelocytic leukemia (APL) with other hematologic diseases in the absence of previous chemotherapy or ionizing radiotherapy treatment is very rare. We present a case of simultaneous occurrence of APL with myelodysplastic syndrome (MDS)-related acute myeloid leukemia (AML). A 43-yearold female presented with 3 month of history fatigue, night sweats, chills and pancytopenia. Bone marrow aspirate and biopsy demonstrated 20% myeloid blasts with dysplastic changes admixed with abnormal promyelocytes. Cytogenetic analysis showed tetraploidy and deletion in chromosomes 5q and 7q and polymerase chain reaction showed presence of PML/RARA mRNA transcripts, confirming the presence of concurrent APL and MDS-related AML. Induction chemotherapy with cytarabine and daunorubicin was initiated along with all-trans retinoic acid. This is the first case to be reported in the literature of concurrent occurrence of APL with MDS-related AML. Treatment with 7 + 3 regimen and ATRA was successful in inducing complete remission.

The evolution of the diminishing role of extrapleural pneumonectomy in the surgical management of malignant pleural mesothelioma.

Malignant pleural mesothelioma is an uncommon and aggressive thoracic malignancy that is rarely curable, even when multimodality therapy is used. Systemic chemotherapy is the primary treatment for the majority of patients with this disease; however, surgical resection may benefit a subset of patients with early-stage disease. The surgical approach that offers the best outcomes remains an area of controversy, with data from retrospective comparisons being the only guide. Historically, extrapleural pneumonectomy (EPP) has been the standard procedure, carrying with it a cost of significant morbidity and impact on quality of life that has raised questions regarding its routine application. Over the past two decades as surgical techniques have been refined and survival data with EPP in large case series have been reported, the paradigm has evolved toward the use of lung-sparing pleural resections such as pleurectomy/decortication (P/D) and extended P/D. The identification of patients who may benefit from EPP over pleurectomy has proven problematic, and the larger question regarding the impact of any type of surgical intervention on outcomes for pleural mesothelioma patients is still an area of investigation. Uniform treatment approaches have been difficult to develop due to the relatively small numbers of patients with this disease, the use of a staging system that does not readily identify those who may benefit from more aggressive therapy, and the institutional biases that have resulted from the growth of multimodality centers of excellence.

Reducing Unplanned Medical Oncology Readmissions by Improving Outpatient Care Transitions: A Process Improvement Project at the Cleveland Clinic.

PURPOSE: Reducing 30-day unplanned hospital readmissions is a national policy priority. We examined the impact of a quality improvement project focused on reducing oncology readmissions among patients with cancer who were admitted to palliative and general medical oncology services at the Cleveland Clinic. METHODS: Baseline rates of readmissions were gathered during the period from January 2013 to April 2014. A quality improvement project designed to improve outpatient care transitions was initiated during the period leading to April 1, 2014, including: (1) provider education, (2) postdischarge nursing phone calls within 48 hours, and (3) postdischarge provider follow-up appointments within 5 business days. Nursing callback components included symptom management, education, medication review/compliance, and follow-up appointment reminder. RESULTS: During the baseline period, there were 2,638 admissions and 722 unplanned 30-day readmissions for an overall readmission rate of 27.4%. Callbacks and 5-day follow-up appointment monitoring revealed a mean monthly compliance of 72% and 78%, respectively, improving over time during the study period. Readmission rates declined by 4.5% to 22.9% (P < .01; relative risk reduction, 18%) during the study period. The mean direct cost of one readmission was $10,884, suggesting an annualized cost savings of $1.04 million with the observed reduction in unplanned readmissions. CONCLUSION: Modest readmission reductions can be achieved through better systematic transitions to outpatient care (including follow-up calls and early provider visits), thereby leading to a reduction in use of inpatient resources. These data suggest that efforts focused on improving outpatient care transition were effective in reducing unplanned oncology readmissions.

Reduction of Inappropriate Prophylactic Pegylated Granulocyte Colony-Stimulating Factor Use for Patients With Non-Small-Cell Lung Cancer Who Receive Chemotherapy: An ASCO Quality Training Program Project of the Cleveland Clinic Taussig Cancer Institute.

PURPOSE: Routine prophylactic pegylated granulocyte colony-stimulating factor (pGCSF) administration for patients receiving chemotherapy regimens associated with low risk (< 10%) for neutropenic fever (LRNF) is not recommended. Inappropriate use of pGCSF increases patient morbidity and health care costs. METHODS: A multidisciplinary team reviewed the charts of patients with non-small-cell lung cancer (NSCLC) at the Taussig Cancer Institute in whom a new chemotherapy regimen was initiated from April through November 2013. pGCSF use was identified and deemed appropriate if prescribed for chemotherapy associated with high risk of neutropenic fever (> 20%) or intermediate risk (10% to 20%) if other risk factors for neutropenic fever were present. Use with LRNF chemotherapy was recorded as inappropriate. RESULTS: One hundred eighty patients with NSCLC received a new chemotherapy regimen during the specified time period. Thirty-four of 119 patients (28%) treated with LRNF chemotherapy received pGCSF. Each patient received an average of 2.6 doses of pGCSF (total, 89 doses). We implemented three plan-do-study-act cycles: education of providers, development of Taussig Cancer Institute consensus guidelines for pGCSF in NSCLC, and removal of standing pGCSF orders from LRNF chemotherapy in the electronic medical record. Analysis during the change period revealed 4% of patients with NSCLC treated with LRNF chemotherapy received pGCSF. Cost analysis showed an 84% decrease in billed charges per month. No increase in neutropenic fever admissions was found. CONCLUSION: pGCSF was excessively prescribed for patients with NSCLC. Factors contributing to inappropriate use included provider lack of familiarity with guidelines and knowledge with regard to the risk of neutropenic fever for individual chemotherapy regimens, and electronic medical record chemotherapy templates that contain standing GCSF orders. Interventions to address these gaps quickly produced improved compliance with guidelines and led to significant cost savings.