Dawn of a new era of antibody-drug conjugates and bispecific T-cell engagers for treatment of multiple myeloma: a systematic review of literature.

Multiple myeloma (MM) remains an incurable disease with the majority of patients experiencing disease relapse despite response to initial therapy. Antibody-drug conjugates (ADCs) and bispecific T-cell engagers are innovative immunotherapeutic approaches currently in development for the treatment of MM. This systematic review summarizes the efficacy and safety of ADCs and bispecific T-cell engagers in relapsed refractory (RR) MM patients from 2010 to date. Comprehensive literature search was conducted on PubMed, EMBASE, Wiley Cochrane Library, Web of Science, and Clinicaltrials.gov . A total of 13 studies (n = 529) met inclusion eligibility. All studies were prospective in nature investigating ADCs or bispecific T-cell engagers in RR MM; 10 trials were phase 1 and 3 were phase 2. The median age of patients ranged from 24 to 82 years. Among trials with ADC regimens, the overall response (OR) ranged from 34 to 60% and complete response (CR) ranged from 3 to 6%. The most common non-hematologic adverse event (AE) of ADCs was keratopathy, while anemia and thrombocytopenia were the most common hematological AEs. With bispecific T-cell engagers , ORR ranged from 31 to 83%, CR ranged from 7 to 22%, and partial response (PR) ranged from 5 to 16%. The most common non-hematologic AE of bispecific T-cell engagers was cytokine release syndrome (CRS) while the most common hematological AE was neutropenia. Initial data appears to show good clinical activity and tolerable safety profiles, making ADCs and bispecific T-cell engagers promising agents for RRMM. Future studies with newer combinations and a longer follow-up are needed to determine the precise role of these novel therapies in the evolving paradigm of MM treatment.

Therapeutic Roles of Antibody Drug Conjugates (ADCs) in Relapsed/Refractory Lymphomas.

Relapsed or refractory lymphoma is commonly treated with combination chemoimmunotherapy and cellular immunotherapy. Modest response rates and associated toxicities are obstacles to achieving durable remission using traditional cytotoxic chemotherapy, especially in frail patients with advanced disease. Antibody drug conjugates represent a new class of novel targeted agents with significant improvement in therapeutic efficacy in the treatment of lymphomas. Several of these agents, which offer improved targeting, greater potency, and better therapeutic index over traditional chemotherapy, are changing the treatment landscape for lymphomas and other hematological malignancies. Despite the therapeutic potential of these agents, the delivery and release of cytotoxic agents to malignant cells through the combination of a monoclonal antibody, payload, and linker represents a complex design challenge. This article reviews the clinical data on currently available antibody drug conjugates and the ongoing development of novel antibody drug conjugates. Antibody drug conjugates constitute an important armamentarium for treatment of lymphomas and their evolving roles in the treatment spectrum are discussed.

Immune-Related Toxicity Among Adolescent and Young Adult with Melanoma as Compared with the Elderly.

Background: Melanoma constitutes ∼8% of malignancies diagnosed among adolescents and young adults (AYA). Although immunotherapy with checkpoint inhibitor (ICI) has become a standard treatment for melanoma, available data on immune-related adverse events (irAE) among AYA population are still limited. Some early reports suggested that irAE may be more frequent among AYA than other age groups. Methods: We performed a retrospective cohort study of melanoma patients who were previously ICI naive and received ICI at our institution during 2007-2019, comparing the incidences of irAE between AYA and elderly patients. AYA cohort was defined as age 15-39 years and elderly cohort was defined as age >65 years at ICI initiation. Results: Analyses included 153 patients: 48 AYA and 105 elderly. The median age was 31.2 and 72.0 years, respectively. The AYA cohort had better performance status and fewer comorbidities than the elderly cohort. A combined ICI regimen, ipilimumab plus nivolumab, was used more frequently among the AYA than the elderly cohort: 25.0% versus 3.8%, p < 0.001. In univariable analyses, AYA experienced more increased liver enzymes, more hospitalization, but less skin rash. After adjusting for baseline characteristics and treatment regimen in multivariable analyses, AYA was independently associated with a lower incidence of skin rash: odds ratio 0.36 (95% confidence interval: 0.14-0.75), p = 0.006. Conclusion: In this large cohort of melanoma patients undergoing first-line immunotherapy, skin rash was less frequent among AYA than the elderly. Although some toxicities may appear more prevalent among AYA, this was attributable to the higher use of combined ICI regimen.

Carfilzomib-induced atypical haemolytic uraemic syndrome: a diagnostic challenge and therapeutic success.

Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy (TMA) that presents with renal insufficiency, thrombocytopaenia and microangiopathic haemolytic anaemia. Typical HUS is associated with Shiga toxin while atypical HUS (aHUS) is due to overactivation of the alternative complement pathway. aHUS has numerous causes, including drugs, with rare reports of carfilzomib, a proteasome inhibitor used in multiple myeloma, as causative agent. Cases vary in presentation, presenting a diagnostic challenge. Historically, TMAs were treated with plasma exchange. aHUS, however, is considered refractory to plasma exchange and best treated with eculizumab, a monoclonal antibody targeting C5, a terminal complement protein. We report a patient with history of multiple myeloma who presented with headaches, elevated blood pressure, petechiae, ecchymosis and haemolytic anaemia. His condition was determined to be carfilzomib-induced aHUS and he was successfully treated with eculizumab. Early detection and treatment of drug-induced aHUS is vital in reducing morbidity and mortality related to the condition.

Awareness, Use and Outlook of Complementary and Alternative Medicine (CAM) Options in an Underserved, Uninsured Minority Cancer Patient Population.

Integrative oncology aims to coordinate the delivery of conventional medicine and evidence-supported complementary and alternative medicine (CAM) to patients receiving cancer care. This field developed out of an increased interest in CAM usage among cancer patients. However, CAM use among medically underserved cancer patients remains to be well characterized. We evaluated CAM awareness as well as prevalence and characteristics of CAM use in 170 consecutive, medically underserved cancer patients presenting to a large, academic, inner-city cancer clinic, using a survey tool. Fifty-three participants declined participation and 17 survey results were incomplete. Therefore, 100 survey results were included in the final analysis. There were 65 males and 35 females in the survey with a mean age of 64.2 years. About 98% of the respondents were African American while 2% identified themselves as Hispanic. About 45% of patients had metastatic cancer, 24% had early-stage disease while 31% of patients were not aware of the stage of their cancer. About 55% patients had elementary school or lower level of education while only 16% had a college degree or higher. About 92% of respondents were unemployed. Some knowledge of CAM was reported by 22% of patients, while CAM use was reported in only 16% of patients. Female sex and college degree were significantly associated with CAM use. The most commonly used CAM modality was meditation (56%), followed by herbal remedies (31%), yoga (31%), and acupuncture (12%). Among CAM users, a majority used multiple CAM therapies. All users reported benefit from CAM use. Emotional wellbeing was the most common benefit followed by improvement in treatment related adverse effects, chemotherapy related symptoms, pain, and sleep. Even though the majority of our surveyed patients never used CAM, 90% of non-users were interested in gaining more information about the various CAM options and exploring its use and potential benefits. The majority (70%) wanted their primary oncologist to provide information about CAM options and discuss its safety and potential complementary benefit in management of their cancer and associated symptoms.

Calcium and vitamin D intake in allergic versus non-allergic children and corresponding parental attitudes towards dairy products.

BACKGROUND: It is hypothesized that parents of children with allergic conditions believe dairy products are potentially harmful to their child. OBJECTIVES: This study compares the calcium and vitamin D intake of allergic versus non-allergic children and parental beliefs about milk and dairy products. METHODS: A survey and food-frequency-questionnaire were administered to parents of children between 3 and 13 years, 110 with allergic disease (allergic rhinitis, asthma, food allergy, and/or atopic dermatitis) versus 110 without allergic disease. Calcium and vitamin D intake was calculated from the food-frequency-questionnaire and compared to National Institutes of Health recommendations. Associations between atopy, calcium and vitamin D intake, and beliefs were investigated using Chi-square test (α = 0.05). Distribution across subjects was investigated using Mann-Whitney-U test (α = 0.05). RESULTS: Fewer allergic (51.8%) versus non-allergic children (77.3%) met the recommended calcium intake (p < 0.001). Both had similar rates of insufficient vitamin D intake: 12.7% allergic and 17.3% non-allergic (p = 0.345). 81.7% of parents of allergic versus 94.0% of non-allergic children believe intake of dairy is important (p = 0.009). 23.7% of parents of allergic versus 8.0% of non-allergic children believe dairy negatively impacts their child (p = 0.003). 19.1% of parents of allergic children (excluding 3 with documented milk allergy) versus 2.0% of non-allergic believe their child is allergic or intolerant to dairy (p < 0.001). CONCLUSIONS: Children are at risk of insufficient calcium and vitamin D intake. Atopic children may be at increased risk for insufficient intake, due in part to parent's negative beliefs regarding dairy products. Physicians should counsel on the importance of micronutrient intake and how allergic conditions do or do not entail dietary restrictions.

Incidence and Management of Effusions Before and After CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy in Large B Cell Lymphoma.

In patients with lymphoma, third-space fluid accumulations may develop or worsen during cytokine release syndrome (CRS) associated with chimeric antigen receptor (CAR) T cell therapy. Pre-existing symptomatic pleural effusions were excluded by the ZUMA-1 trial of axicabtagene ciloleucel for large B cell lymphoma (LBCL) and variants. The incidence and management of effusions during CAR T cell therapy for LBCL are unknown. We performed a single-center retrospective study evaluating 148 patients receiving CD19-directed CAR T cell therapy for LBCL between May 2015 and September 2019. We retrospectively identified patients who had radiographic pleural, pericardial, or peritoneal effusions that were present prior to the time of CAR T infusion (pre-CAR T) or that newly developed during the first 30 days after CAR T-cell infusion (post-CAR T). Of 148 patients, 19 patients had a pre-CAR T effusion, 17 patients without pre-existing effusion developed a new infusion after CAR T, and 112 patients had no effusions. Comparing pre-CAR T effusions to new effusions post-CAR T, pre-CAR T effusions were more often malignant (84% versus 12%), persistent beyond 30 days (95% versus 18%), and required interventional drainage after CAR T infusion (79% versus 0%). Compared to patients with no effusion, patients with pre-CAR T therapy effusions had a higher frequency of high-risk baseline characteristics, such as bulky disease and high International Prognostic Index. Similarly, patients with pre-CAR T therapy effusions had a higher rate of toxicity with grade 3 or higher CRS occurring in 32% of patients. On multivariate analysis adjusting for age, Eastern Cooperative Oncology Group status, bulky disease, albumin, and lactate dehydrogenase, a pre-CAR T therapy effusion was associated with reduced overall survival (hazard ratio, 2.34; 95% confidence interval, 1.09 to 5.03; P = .03). Moreover, there was higher non-relapse mortality (11% versus 1%; P = .005). Post-CAR T effusions were not associated with significant difference in survival. Effusions commonly complicate CAR T cell therapy for lymphoma. Malignant effusions that occur prior to CAR T therapy are frequently persistent and require therapeutic intervention, and patients have a higher rate of toxicity and death. Effusions that newly occur after CAR T therapy can generally be managed medically and tend not to persist.