Patient Perceptions of CAR-T Therapy in the USA: Findings from In-Depth Interviews.

INTRODUCTION: Chimeric antigen receptor-T cell (CAR-T) therapy has revolutionized advanced blood cancer treatment. However, preparation, administration, and recovery from these therapies can be complex and burdensome to patients and their care partners. Utilization of an outpatient setting for CAR-T therapy administration could help improve convenience and quality of life. METHODS: In-depth qualitative interviews were conducted with 18 patients in the USA with relapsed/refractory multiple myeloma or relapsed/refractory diffuse large B-cell lymphoma, 10 of whom had completed investigational or commercially approved CAR-T therapy and 8 of whom had discussed it with their physicians. We aimed to better understand inpatient experiences and patient expectations regarding CAR-T therapy and to ascertain patient perspectives on the possibility of outpatient care. RESULTS: CAR-T offers unique treatment benefits, particularly high response rates with an extended treatment-free period. All study participants completing CAR-T were very positive about their inpatient recovery experience. Most reported mild-to-moderate side effects; two experienced severe side effects. All said that they would opt to undergo CAR-T therapy again. Participants felt that the primary advantage of inpatient recovery was immediate access to care and on-going monitoring. Perceived advantages of the outpatient setting were comfort and familiarity. Because immediate access to care was seen as crucial, patients recovering in an outpatient setting would seek either a direct contact person or phone line for assistance if needed. CONCLUSION: As institutions become more experienced with CAR-T therapies, outpatient care may help reduce financial strain. Patient input can help institutions improve the outpatient experience and ensure safety and effectiveness of CAR-T programs.

CRISPR-engineered T cells in patients with refractory cancer.

CRISPR-Cas9 gene editing provides a powerful tool to enhance the natural ability of human T cells to fight cancer. We report a first-in-human phase 1 clinical trial to test the safety and feasibility of multiplex CRISPR-Cas9 editing to engineer T cells in three patients with refractory cancer. Two genes encoding the endogenous T cell receptor (TCR) chains, TCRα (TRAC) and TCRß (TRBC), were deleted in T cells to reduce TCR mispairing and to enhance the expression of a synthetic, cancer-specific TCR transgene (NY-ESO-1). Removal of a third gene encoding programmed cell death protein 1 (PD-1; PDCD1), was performed to improve antitumor immunity. Adoptive transfer of engineered T cells into patients resulted in durable engraftment with edits at all three genomic loci. Although chromosomal translocations were detected, the frequency decreased over time. Modified T cells persisted for up to 9 months, suggesting that immunogenicity is minimal under these conditions and demonstrating the feasibility of CRISPR gene editing for cancer immunotherapy.

Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma.

BACKGROUND: Multiple myeloma is usually fatal due to serial relapses that become progressively refractory to therapy. CD19 is typically absent on the dominant multiple myeloma cell population but may be present on minor subsets with unique myeloma-propagating properties. To target myeloma-propagating cells, we clinically evaluated autologous T cells transduced with a chimeric antigen receptor (CAR) against CD19 (CTL019). METHODS: Subjects received CTL019 following salvage high-dose melphalan and autologous stem cell transplantation (ASCT). All subjects had relapsed/refractory multiple myeloma and had previously undergone ASCT with less than 1 year progression-free survival (PFS). RESULTS: ASCT + CTL019 was safe and feasible, with most toxicity attributable to ASCT and no severe cytokine release syndrome. Two of 10 subjects exhibited significantly longer PFS after ASCT + CTL019 compared with prior ASCT (479 vs. 181 days; 249 vs. 127 days). Correlates of favorable clinical outcome included peak CTL019 frequency in bone marrow and emergence of humoral and cellular immune responses against the stem-cell antigen Sox2. Ex vivo treatment of primary myeloma samples with a combination of CTL019 and CAR T cells against the plasma cell antigen BCMA reliably inhibited myeloma colony formation in vitro, whereas treatment with either CAR alone inhibited colony formation inconsistently. CONCLUSION: CTL019 may improve duration of response to standard multiple myeloma therapies by targeting and precipitating secondary immune responses against myeloma-propagating cells. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02135406. FUNDING: Novartis, NIH, Conquer Cancer Foundation.

CAR T-Cell Therapy: On the Verge of Breakthrough in Many Hematologic Malignancies.

There have been promising results from clinical trials on the efficacy of engineering patients' immune cells to treat their cancers. CAR T-cell therapy also has unique toxicities advanced practitioners should be aware of.

Financial toxicity in insured patients with multiple myeloma: a cross-sectional pilot study.

BACKGROUND: Financial toxicity is increasingly recognised as adversely affecting the quality of life and medication adherence in patients with cancer in the USA. Patients with multiple myeloma might be particularly vulnerable because of high use of novel treatments and extended treatment duration. METHODS: Between Aug 18, 2014, and Jan 7, 2015, we did a cross-sectional survey of individuals receiving at least 3 months of ongoing treatment for multiple myeloma at a tertiary academic medical centre in the USA. The survey was derived from previous reported studies and included the 11-item COST measure (financial toxicity score range 0-44). A paper survey was offered to eligible patients on arrival for routine follow-up visits, and participants were asked to complete the survey before or after their visit to the clinic. Insurance and treatment data were obtained from patients' electronic health records. FINDINGS: Of 111 patients approached for the study, 100 individuals completed the survey. 59 (59%) of 100 patients reported that treatment costs were higher than expected, 70 (71%) of 99 had at least minor financial burden, and 36 (36%) of 100 reported applying for financial assistance. Use of savings to pay for myeloma treatment was common (43 [46%] of 94 patients) and 21 (21%) of 98 individuals borrowed money to pay for medications. COST scores were highly correlated with patient-reported use of strategies to cope with myeloma treatment expenses. On multivariable analysis, younger age (correlation coefficient ß 0·36, 95% CI 0·15 to 0·56, p=0·00092), non-married status (5·6, 1·5 to 9·6, p=0·0074), longer duration since diagnosis (-4·8, -9·3 to -0·2, p=0·042), and lower household income (US$40 000-79 999: 7·8, 2·7 to 12·9, p=0·0031; ≥$80 000: 11·8, 7·1 to 16·4, p<0·0001) were associated with higher financial burden as measured with the COST score. INTERPRETATION: Patient-reported financial toxicity and use of coping mechanisms were common in our insured population with multiple myeloma. Additional attention to rising treatment costs and cost sharing is needed to address the increasing evidence of financial toxicity affecting patients with cancer. FUNDING: University of Pennsylvania Perelman School of Medicine.

Autologous hematopoietic stem cell transplantation for patients with multiple myeloma: an overview for nurses in community practice.

Autologous hematopoietic stem cell transplantation (AHSCT) is approved for the treatment of select solid tumors, autoimmune disorders, and most hematologic malignancies. Multiple myeloma (MM) is the most common indication for AHSCT. Despite improvement in response and survival rates in the era of novel agents, AHSCT remains an important treatment option for patients with MM who are eligible. Clinical management of patients with MM requires a multidisciplinary approach that incorporates healthcare professionals in a number of clinical settings as well as caregivers and the patient. Patients about to undergo AHSCT are generally referred to tertiary care centers that specialize in ASCT. Pre- and post-transplantation treatments and long-term follow-up often are managed by a community-based referring oncologist in collaboration with the transplantation team. Oncology nurses play an integral role in the care of patients with MM in each clinical setting. This article aims to provide non-transplantation oncology nurses with guidelines for education, clinical management, and support of patients with MM undergoing AHSCT with a primary focus on the pre- and post-transplantation period.

Autologous hematopoietic stem cell transplantation for multiple myeloma: frequently asked questions.

When caring for patients with multiple myeloma, questions often arise about the role and timing of autologous hematopoietic stem cell transplantation. As a complement to the other articles in this supplement, as well as to ensure that readers are provided with the insight needed to feel comfortable speaking to patients and other practitioners about this topic, the authors address eight frequently asked questions about common decision points in the process of autologous hematopoietic stem cell transplantation as a treatment for patients with multiple myeloma.

Transfer of influenza vaccine-primed costimulated autologous T cells after stem cell transplantation for multiple myeloma leads to reconstitution of influenza immunity: results of a randomized clinical trial.

Severe immune deficiency follows autologous stem cell transplantation for multiple myeloma and is associated with significant infectious morbidity. This study was designed to evaluate the utility of a pretransplantation vaccine and infusion of a primed autologous T-cell product in stimulating specific immunity to influenza. Twenty-one patients with multiple myeloma were enrolled from 2007 to 2009. Patients were randomly assigned to receive an influenza-primed autologous T-cell product or a nonspecifically primed autologous T-cell product. The study endpoint was the development of hemagglutination inhibition titers to the strain-specific serotypes in the influenza vaccine. Enzyme-linked immunospot assays were performed to confirm the development of influenza-specific B-cell and T-cell immunity. Patients who received the influenza-primed autologous T-cell product were significantly more likely to seroconvert in response to the influenza vaccine (P = .001). Seroconversion was accompanied by a significant B-cell response. No differences were observed in the global quantitative recovery of T-cell and B-cell subsets or in global T-cell and B-cell function. The provision of a primed autologous T-cell product significantly improved subsequent influenza vaccine responses. This trial was registered at www.clinicaltrials.gov as #NCT00499577.

Management of side effects of novel therapies for multiple myeloma: consensus statements developed by the International Myeloma Foundation's Nurse Leadership Board.

Nurses play an essential role in managing the care of patients with multiple myeloma, who require education and support to receive and adhere to optimal therapy. The International Myeloma Foundation created a Nurse Leadership Board comprised of oncology nurses from leading cancer centers and community practices. An assessment survey identified the need for specific recommendations for managing key side effects of novel antimyeloma agents. Myelosuppression, thromboembolic events, peripheral neuropathy, steroid toxicities, and gastrointestinal side effects were selected for the first consensus statements. The board developed recommendations for healthcare providers in any medical setting, including grading of side-effect toxicity and strategies for managing the side effects in general, with specific recommendations pertaining to the novel agents.

Steroid-associated side effects in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board.

Steroids have been the foundation of multiple myeloma therapy for more than 30 years and continue to be prescribed as single agents and in combination with other antimyeloma drugs, including novel therapies. Steroids cause a wide range of side effects that affect almost every system of the body. Identification and prompt management of the toxicities contribute to the success of steroid-containing antimyeloma regimens. By following patients carefully and educating them and their caregivers, nurses can promote adherence to therapy and improve quality of life. The International Myeloma Foundation's Nurse Leadership Board developed this consensus statement for the management of steroid-associated side effects to be used by healthcare providers in any medical setting.

Impact of EmbryoGlue as the embryo transfer medium.

Routine use of EmbryoGlue did not significantly improve pregnancy or implantation rates in nonselected patients receiving either a day 3 or day 5 embryo transfer compared with standard culture media. Future prospective randomized studies need to be performed to determine whether EmbryoGlue is beneficial in a selected patient population.

Post-transplant outcomes of induction therapy for myeloma: thalidomide and dexamethasone versus doxorubicin, vincristine, and dexamethasone prior to high-dose melphalan with autologous stem cell support.

High-dose melphalan with autologous stem cell support improves survival as part of initial therapy for myeloma. Previous studies of pre-transplant induction regimens have compared paraprotein response rates but not long-term outcomes after transplant. We reviewed the records of all patients with multiple myeloma who received an autologous stem cell transplant at the University of Pennsylvania Medical Center. We compared outcomes for 69 patients who received high-dose melphalan conditioning after January 1, 2003 as part of initial therapy for myeloma, including 41 patients who received anthracycline-based induction (VAD or DVD) and 28 patients who received thalidomide and dexamethasone induction. Baseline characteristics in these two groups were not different, though potentially clinically important differences were apparent in assignment to post-transplant consolidation and maintenance therapy. Despite similar response rates during induction therapy, thalidomide and dexamethasone induction was associated with better progression-free survival (hazard ratio 0.18, P = 0.011) after transplant. This effect persisted in multivariable regression models including baseline characteristics and post-transplant treatment. Overall survival was not different between the two groups. These results suggest that the use of thalidomide during induction therapy may lead to improved long-term outcomes after transplant. Future trials comparing induction therapies should examine progression-free and overall survival after transplant to confirm this benefit.

Caregiving at the end of life: Perceptions of health care quality and quality of life among patients and caregivers.

This study explored the association between perceptions of health care quality and quality of life in patients with advanced metastatic cancer and their informal caregivers (n=39). Patients' and caregivers' perceptions of health care quality, mental health, health-related quality of life, symptoms, and burden were measured. The key findings included the following: 1) patients' mental health and depression scores correlated with those of caregivers, suggesting that the mental health of patients and their caregivers are associated; 2) patients and caregivers shared similar perceptions regarding health care quality; 3) the presence of depression in caregivers correlated with caregivers being less satisfied with the health care being given to their patients (this correlation did not exist for patients, a finding that may be due in part to the protective buffering effect that caregivers provide their patients as illness progresses); and 4) a modified Primary Care Assessment Survey, originally designed for primary care patients, was a useful measure of health care assessment for both patients and caregivers. These data suggest that patients with advanced disease and their caregivers share similar perceptions and evolve as a "unit of care," and caregivers, as unique and important members of the patient's health care team, are also in need of care. When depressed, caregivers may unilaterally lose trust by becoming less satisfied with the quality of health care being provided to their patients.

Caregiving near the end of life: unmet needs and potential solutions.

OBJECTIVE: A key aspect of the role of clinicians caring for patients in the setting of advanced illness focuses on attending to the needs of informal caregivers during the end-of-life period. The purpose of this study was twofold: (1) to complement and enrich existing quantitative findings regarding caregiver burden near the end of life, and (2) to identify potential solutions to caregivers' unmet needs in an effort to assist clinicians in the development of clinical interventions. METHODS: This qualitative study, using focus groups and content analysis of transcripts, was conducted in a comprehensive cancer center in Washington, DC. Seven focus groups were held: three with recently bereaved caregivers and four with active caregivers of patients with metastatic cancer and an expected survival of 6 to 12 months. RESULTS: Data were stratified into two broad categories: (1) general problems and (2) behaviors/activities that were helpful/would have been helpful in alleviating these problems. Within each of these two categories, five subcategories emerged: medical care (including provision of information, coordination of care, bedside manner, satisfaction with care), quality of life (including well-being, role adjustments), help from others (including practical assistance, social support), positives of caregiving, and unsolicited themes (including job flexibility, impact of the disease on the family, informational needs, relationship with patient). SIGNIFICANCE OF RESULTS: Results suggest caregivers may benefit from more information about patient prognosis and hospice, attention to quality-of-life issues, and enhanced, direct communication with clinicians. Although information of this nature is likely to be known to palliative care clinicians, the specific details and verbal insights provided by caregivers give an important voice to existing quantitative data and may provide more detailed information to assist palliative care clinicians seeking to develop interventions to meet caregiver needs during the period near the end of life.