A Focus on Relapsed Multiple Myeloma.

Multiple myeloma (MM) is a relapsing disease for many patients with multiple myeloma. At relapse, patients have many options for treatment once disease has progressed. Advanced practitioners are well suited to set expectations for ongoing therapy and underscore the importance of continued disease monitoring. Criteria for relapsed myeloma rely on biomarker and radiologic imaging, as well as physical exam and awareness of new bone pain or changes in physiologic function. The treatment of patients with relapsed MM requires a personalized approach and considers patient desires in regard to aggressiveness of therapy and willingness to participate in a clinical trial. The prognosis of patients with relapsed MM depends upon disease characteristics at baseline or throughout, as patients may acquire adverse cytogenetic abnormalities through various lines of treatment. Empowering patients to understand their diagnosis, interpret labs, and take an active role in treatment selection through shared decision-making can improve patients' quality of life and enhance adherence.

An Allogeneic Multiple Myeloma GM-CSF-Secreting Vaccine with Lenalidomide Induces Long-term Immunity and Durable Clinical Responses in Patients in Near Complete Remission.

PURPOSE: This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF-secreting vaccine (MM-GVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR). PATIENTS AND METHODS: Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months. RESULTS: Eight patients (53.3%) achieved a true CR. With a median follow-up of 5 years, the median progression-free survival had not been reached, and the median overall survival was 7.8 years from enrollment. MM-GVAX induced clonal T-cell expansion and measurable cytokine responses that persisted up to 7 years in all patients. At baseline, a higher minimal residual disease was predictive of early relapse. After vaccination, a lack of both CD27-DNAM1-CD8+ T cells and antigen-presenting cells was associated with disease progression. CONCLUSIONS: MM-GVAX, along with lenalidomide, effectively primed durable immunity and resulted in long-term disease control, as suggested by the reappearance of a detectable, fluctuating M-spike without meeting the criteria for clinical relapse. For patients in a nCR, MM-GVAX administration was safe and resulted in prolonged clinical responses.

Antiemetics: ASCO Guideline Update.

PURPOSE: To update the guideline to include new anticancer agents, antiemetics, and antiemetic regimens and to provide recommendations on the use of dexamethasone as a prophylactic antiemetic in patients receiving checkpoint inhibitors (CPIs). METHODS: ASCO convened an Expert Panel and updated the systematic review to include randomized controlled trials (RCTs) and meta-analyses of RCTs published between June 1, 2016, and January 24, 2020. To address the dexamethasone and CPI question, we conducted a systematic review of RCTs that evaluated the addition of a CPI to chemotherapy. RESULTS: The systematic reviews included 3 publications from the updated search and 10 publications on CPIs. Two phase III trials in adult patients with non-small-cell lung cancers evaluating a platinum-based doublet with or without the programmed death 1 (PD-1) inhibitor pembrolizumab recommended that all patients receive dexamethasone as a component of the prophylactic antiemetic regimen. In both studies, superior outcomes were noted in the PD-1 inhibitor-containing arms. Other important findings address olanzapine in adults and fosaprepitant in pediatric patients. RECOMMENDATIONS: Recommendations for adults are unchanged with the exception of the option of adding olanzapine in the setting of hematopoietic stem cell transplantation. Dosing information now includes the option of a 5-mg dose of olanzapine in adults and intravenous formulations of aprepitant and netupitant-palonosetron. The option of fosaprepitant is added to pediatric recommendations. There is no clinical evidence to warrant omission of dexamethasone from guideline-compliant prophylactic antiemetic regimens when CPIs are administered to adults in combination with chemotherapy. CPIs administered alone or in combination with another CPI do not require the routine use of a prophylactic antiemetic.Additional information is available at www.asco.org/supportive-care-guidelines.

Oncology Nurse Practitioner Competencies: Defining Best Practices in the Oncology Setting.

BACKGROUND: The oncology nurse practitioner (ONP) role has evolved since the first ONP competencies were published by the Oncology Nursing Society in 2007. An update was completed in 2019 to reflect the rapidly expanding role. OBJECTIVES: The purpose of this article is to describe the process of the ONP competency development and identify potential applications across a variety of oncology settings. METHODS: The team performed an extensive literature review of the research about ONP practice across the cancer care continuum. Peer and expert review were conducted to ensure the competencies were comprehensive and relevant. FINDINGS: The ONP competencies provide a solid, evidence-based benchmark to standardize the ONP role and practice, thereby ensuring that patients receive the highest-quality cancer care.

Phase I/II trial of the CXCR4 inhibitor plerixafor in combination with bortezomib as a chemosensitization strategy in relapsed/refractory multiple myeloma.

We tested the hypothesis that using CXCR4 inhibition to target the interaction between the tumor cells and the microenvironment leads to sensitization of the tumor cells to apoptosis. Eligibility criteria included multiple myeloma (MM) patients with 1-5 prior lines of therapy. The purposes of the phase I study were to evaluate the safety and maximal-tolerated dose (MTD) of the combination. The treatment-related adverse events and response rate of the combination were assessed in the phase II study. A total of 58 patients were enrolled in the study. The median age of the patients was 63 years (range, 43-85), and 78% of them received prior bortezomib. In the phase I study, the MTD was plerixafor 0.32 mg/kg, and bortezomib 1.3 mg/m2 . The overall response rate for the phase II study was 48.5%, and the clinical benefit rate 60.6%. The median disease-free survival was 12.6 months. The CyTOF analysis demonstrated significant mobilization of plasma cells, CD34+ stem cells, and immune T cells in response to plerixafor. This is an unprecedented study that examines therapeutic targeting of the bone marrow microenvironment and its interaction with the tumor clone to overcome resistance to therapy. Our results indicate that this novel combination is safe and that the objective response rate is high even in patients with relapsed/refractory MM. ClinicalTrials.gov, NCT00903968.

Activated Allogeneic Donor-derived Marrow-infiltrating Lymphocytes Display Measurable In Vitro Antitumor Activity.

A major limitation in current allogeneic hematopoietic stem cell transplantation (alloHSCT) is disease relapse after transplant, indicating that donor-derived T cells are inadequate in imparting an effective antitumor response. The current standard treatment approach to relapse utilizes donor lymphocyte infusions that have limited documented efficacy and are also associated with significant morbidity mainly related to graft-versus-host disease. We have previously shown that marrow-infiltrating lymphocytes (MILs) have a broader antigenic specificity compared with their peripheral blood counterpart in an autologous adoptive T-cell therapy setting. Here, we extend these observations to examine the ability of MILs obtained from patients after an alloHSCT to generate measurable tumor-specific immunity. We show here that allogeneic donor-derived marrow-infiltrating lymphocytes (ddMILs) obtained from patients who underwent alloHSCT with posttransplant cyclophosphamide could be reproducibly expanded and activated with anti-CD3/CD28 beads. Phenotypic characterization of ddMILs subpopulations revealed the prevalence of a central memory phenotype. Polyclonally activated ddMILs displayed measurable in vitro antitumor activity. Furthermore, activated ddMILs from all patients effectively targeted third-party allogeneic antigens, but showed no reactivity toward self-antigens presented in an HLA-restricted manner. Collectively, these results underscore the intrinsic polyclonal tumor-specificity of activated ddMILs and describe a novel approach for the generation of tumor-specific T cells that are suitable for adoptive immunotherapy of hematological malignancies relapsed after alloHSCT. This approach has a potential to significantly increase the tumor-specificity and reduce the toxicities associated with current standard donor lymphocyte infusion approaches.

Oncology Nurse Practitioner Role: Recommendations From the Oncology Nursing Society's Nurse Practitioner Summit.

BACKGROUND: Oncology nurse practitioners (ONPs) are advanced practice RNs prepared at the graduate level with high-level knowledge and skills in oncology. Because of challenges in educational programs and variability in the scope of practice at the state and institutional level, many ONPs are challenged to practice to the full extent of their education, certification, and licensure. OBJECTIVES: The purpose of this article is to review issues affecting the education and practice patterns of ONPs and to identify solutions to address the challenges that exist for ONPs. METHODS: Members of the Oncology Nursing Society's Nurse Practitioner Summit summarized the challenges faced by ONPs related to education, training, practice, and professional development. FINDINGS: Efforts to promote ONP practice at the fullest extent of licensure and across various settings should be prioritized. Resources must be devoted to education, onboarding, and retention to integrate and retain ONPs as leaders of the interprofessional team.

Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFß enhance the efficacy of cancer immunotherapy.

A majority of cancers fail to respond to immunotherapy with antibodies targeting immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed death-1 (PD-1)/PD-1 ligand (PD-L1). Cancers frequently express transforming growth factor-ß (TGFß), which drives immune dysfunction in the tumor microenvironment by inducing regulatory T cells (Tregs) and inhibiting CD8+ and TH1 cells. To address this therapeutic challenge, we invent bifunctional antibody-ligand traps (Y-traps) comprising an antibody targeting CTLA-4 or PD-L1 fused to a TGFß receptor II ectodomain sequence that simultaneously disables autocrine/paracrine TGFß in the target cell microenvironment (a-CTLA4-TGFßRIIecd and a-PDL1-TGFßRIIecd). a-CTLA4-TGFßRIIecd is more effective in reducing tumor-infiltrating Tregs and inhibiting tumor progression compared with CTLA-4 antibody (Ipilimumab). Likewise, a-PDL1-TGFßRIIecd exhibits superior antitumor efficacy compared with PD-L1 antibodies (Atezolizumab or Avelumab). Our data demonstrate that Y-traps counteract TGFß-mediated differentiation of Tregs and immune tolerance, thereby providing a potentially more effective immunotherapeutic strategy against cancers that are resistant to current immune checkpoint inhibitors.

Flow cytometric discrimination of seven lineage markers by using two fluorochromes.

Flow cytometry is the primary immunological technique used to analyze multiple parameters on complex cell populations. We present a staining method that identifies major human mononuclear lymphoid and myeloid populations (CD4+ and CD8+ T cells, γδ T cells, B cells, NK cells and monocytes), using only two fluorochromes and a minimal number of cells. Our approach increases the number of markers recordable on most flow cytometers allowing for a deeper and more comprehensive immunophenotyping.

Bone Health, Pain, and Mobility: Evidence-Based Recommendations for Patients With Multiple Myeloma

BACKGROUND: About 85% of patients with multiple myeloma develop bone disease. In these patients, lytic bone lesions can cause fractures, poor circulation, blood clots, pain, poor mobility, and decreased quality of life.
. OBJECTIVES: This article presents consensus statements to guide nurses in the assessment and management of bone disease, pain, and mobility in patients with multiple myeloma at varying points in their disease trajectory.
. METHODS: Members of the International Myeloma Foundation Nurse Leadership Board reviewed previously provided recommendations, current recommendations based on literature review, and evidence-based grading.
. FINDINGS: Oncology nurses play a key role in maximizing bone health, minimizing skeletal injury, maximizing pain control, and improving quality of life in patients by enhancing patient mobility and safety. Clinician assessment accompanied by effective interventions reduces patient injury and optimizes functioning in patients with multiple myeloma.

Distress, Fatigue, and Sexuality: Understanding and Treating Concerns and Symptoms in Patients With Multiple Myeloma 
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BACKGROUND: The psychological needs of patients and caregivers may be inadvertently overlooked, contributing to the patient's distress and possibly compromising outcomes. Untreated, these psychological needs may impair the patient's ability to make decisions and adhere to treatment. 
. OBJECTIVES: This article aims to present consensus statements to guide oncology nurses in the recognition and management of distress, fatigue, and sexual dysfunction in patients with multiple myeloma (MM). 
. METHODS: Members of the International Myeloma Foundation Nursing Leadership Board reviewed the current literature and clinical experience regarding interventions related to distress, fatigue, and sexual dysfunction in patients with MM.
. FINDINGS: Ongoing patient education and attention to medical and psychological care is important to assess and address patients' needs, such as cancer-related fatigue, sexual dysfunction, and distress.

Heart and Lung Complications: Assessment and Prevention of Venous Thromboembolism and Cardiovascular Disease in Patients With Multiple Myeloma
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BACKGROUND: Venous thromboembolism (VTE) and cardiovascular (CV) disease can occur in patients with multiple myeloma. Although VTE and CV disease are separate medical conditions, they can be serious and even life-threatening.
. OBJECTIVES: The objectives of this article are to describe risk factors for cancer-associated VTE, describe the influence of CV disease on patients with multiple myeloma, and review the approaches to VTE and CV disease identification and treatment.
. METHODS: PubMed and CINAHL® databases were used to identify literature to describe VTE and CV in patients diagnosed with multiple myeloma.
. FINDINGS: When present in patients with multiple myeloma, VTE and CV disease can limit patient tolerance for myeloma treatment and, therefore, decrease therapeutic options.

Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update.

Purpose To update the ASCO guideline for antiemetics in oncology. Methods ASCO convened an Expert Panel and conducted a systematic review of the medical literature for the period of November 2009 to June 2016. Results Forty-one publications were included in this systematic review. A phase III randomized controlled trial demonstrated that adding olanzapine to antiemetic prophylaxis reduces the likelihood of nausea among adult patients who are treated with high emetic risk antineoplastic agents. Randomized controlled trials also support an expanded role for neurokinin 1 receptor antagonists in patients who are treated with chemotherapy. Recommendation Key updates include the addition of olanzapine to antiemetic regimens for adults who receive high-emetic-risk antineoplastic agents or who experience breakthrough nausea and vomiting; a recommendation to administer dexamethasone on day 1 only for adults who receive anthracycline and cyclophosphamide chemotherapy; and the addition of a neurokinin 1 receptor antagonist for adults who receive carboplatin area under the curve ≥ 4 mg/mL per minute or high-dose chemotherapy, and for pediatric patients who receive high-emetic-risk antineoplastic agents. For radiation-induced nausea and vomiting, adjustments were made to anatomic regions, risk levels, and antiemetic administration schedules. Rescue therapy alone is now recommended for low-emetic-risk radiation therapy. The Expert Panel reiterated the importance of using the most effective antiemetic regimens that are appropriate for antineoplastic agents or radiotherapy being administered. Such regimens should be used with initial treatment, rather than first assessing the patient's emetic response with less-effective treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .

Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy.

BACKGROUND: Changes in adaptive immune cells after chemotherapy in adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine the functional capacity of the immune system in adult patients with AML who have completed chemotherapy and are potential candidates for immunotherapy. METHODS: We used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system in 10 AML patients in a complete remission post-chemotherapy and performed genetic, phenotypic, and functional characterization of adaptive immune cell subsets. RESULTS: Only 2 patients generated protective titers in response to vaccination, and a majority of patients had abnormal frequencies of transitional and memory B-cells. B-cell receptor sequencing showed a B-cell repertoire with little evidence of somatic hypermutation in most patients. Conversely, frequencies of T-cell populations were similar to those seen in healthy controls, and cytotoxic T-cells demonstrated antigen-specific activity after vaccination. Effector T-cells had increased PD-1 expression in AML patients least removed from chemotherapy. CONCLUSION: Our results suggest that while some aspects of cellular immunity recover quickly, humoral immunity is incompletely reconstituted in the year following intensive cytotoxic chemotherapy for AML. The observed B-cell abnormalities may explain the poor response to vaccination often seen in AML patients after chemotherapy. Furthermore, the uncoupled recovery of B-cell and T-cell immunity and increased PD-1 expression shortly after chemotherapy might have implications for the success of several modalities of immunotherapy.

Immunomodulatory Agents and Proteasome Inhibitors in the Treatment of Multiple Myeloma.

OBJECTIVE: To review the current evidence on the use of immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) in the treatment of multiple myeloma (MM). DATA SOURCES: Journal articles, research reports, state of the science papers, and clinical guidelines. CONCLUSION: There has been a tremendous increase of new agents to treat multiple myeloma in the last 15 years. The IMiDs and PIs remain essential components of many anti-myeloma regimens. IMPLICATIONS FOR NURSING PRACTICE: With these advances in the therapeutic landscape, knowledge of these drugs, side effects and nursing implications are essential to improve outcomes. Patient education is also of vital importance in achieving optimal responses to treatment.

Marrow-Infiltrating Lymphocytes - Role in Biology and Cancer Therapy.

The past several years have witnessed the acceptance of immunotherapy into the mainstream of therapies for patients with cancer. This has been driven by the clinical successes of antibodies to the checkpoint inhibitors, CTLA-4 and PD-1, capable of imparting long-term remissions in several solid tumors as well as Hodgkin's lymphoma (1) and the therapeutic successes of adoptive T-cell transfer with chimeric antigen receptors (2) or modified T-cell receptors (3) that have mostly utilized peripheral T-cells. One emerging area of therapeutic T cell intervention has been the utilization of marrow-infiltrating lymphocytes (MILs) - a novel form of adoptive T-cell therapy. This approach was initially developed to increase the likelihood of a precursor T-cell population with an enhanced tumor specificity in bone marrow (BM)-derived malignancies. However, the unique attributes of BM T-cells and their interaction with their microenvironment provide significant rationale to utilize these cells therapeutically in diseases that extend beyond hematologic malignancies.