Flammia RS, Hoeh B, Hohenhorst L
… +15 more, Sorce G, Chierigo F, Panunzio A, Tian Z, Saad F, Leonardo C, Briganti A, Antonelli A, Terrone C, Shariat SF, Graefen M, Chun FKH, Montorsi F, Gallucci M, Karakiewicz PI
BACKGROUND: Data in patients with malignant melanoma, who have been previously treated with pembrolizumab as adjuvant therapy, show a reduction in pembrolizumab efficacy upon rechallenge. We examined this scenario in pat...BACKGROUND: Data in patients with malignant melanoma, who have been previously treated with pembrolizumab as adjuvant therapy, show a reduction in pembrolizumab efficacy upon rechallenge. We examined this scenario in patients with non-metastatic renal cell carcinoma (RCC) eligible for adjuvant pembrolizumab after nephrectomy. We hypothesized that a proportion of such patients will either require re-treatment with pembrolizumab upon metastatic progression prior to cancer-specific mortality (CSM) or die from other cause mortality (OCM). MATERIALS AND METHODS: We identified within the SEER database 10,635 patients, between 2004 and 2017, with a diagnosis of non-metastatic intermediate-high and high risk RCC, who had undergone nephrectomy and fulfilled criteria for enrollment in KEYNOTE-564. Kaplan-Meier analyses addressed overall survival (OS), CSM and OCM. RESULTS: 9,825 (92.4%) of the 10,635 patients had intermediate-high risk RCC and 9,456 (88.9%) underwent radical nephrectomy. Additionally, 760 (7.1%) harbored sarcomatoid features. In Kaplan-Meier analyses, median OS was 9.8 (9.1-11.4) years. At 10-years of follow-up, CSM rate was 36% and OCM rate was 22%. CONCLUSIONS: Based on CSM, our observations indicate that by 10-years of follow-up 36% of patients treated with adjuvant pembrolizumab will require a rechallenge, in a setting where a checkpoint inhibitor may have reduced efficacy. Moreover, at 10-years of follow-up, 22% of patients with RCC, previously treated with adjuvant pembrolizumab, will die of other causes. These percentages should be strongly considered prior to routine use of adjuvant pembrolizumab, especially given an OS benefit has not been proven.
Costa GJ, Júnior HAF, Malta FC
… +5 more, Bitu FCL, Barbosa C, de Sá J, Amarante A, Thuler LCS
Semin Oncol
· 2022 Apr · PMID 35606169
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INTRODUCTION: Patients with cancer need to receive their proper treatment and often cannot wait for their treatment, despite delays due to the COVID-19 pandemic. As a result, many cancer centers have had challenges maint...INTRODUCTION: Patients with cancer need to receive their proper treatment and often cannot wait for their treatment, despite delays due to the COVID-19 pandemic. As a result, many cancer centers have had challenges maintaining their oncological activities. OBJECTIVES: To compare the average hospital management data and indicators in two different periods, with and without the peak of COVID-19 cases, from an important tertiary cancer center in the northeast region of Brazil. METHODS: A retrospective and observational study was performed comparing average hospital administrative data and indicators, between January to March v April to June, 2020 exclusively at the Hospital de Câncer de Pernambuco, Brazil. RESULTS: There were on average a 13% reduction in the chemotherapy administered (P = .131), 17% fewer radiotherapy treatments carried out (P = .043) and 41% as many oncologic surgeries undertaken (P = .002). There was a reduction in the number of sessions of out-patient chemotherapy of 8•6% (P = .271) and chemotherapy inpatients of 33% (P = .038). Admission of new cases of patients with cancer was reduced by 44% (P = .007) during the period analyzed. Ambulatory appointments also decreased by 55% (P = .004) and emergency room appointments fell by 7•9% (P = .495). The number of hospitalizations was reduced by 36% (P = .005) and the occupancy rate decreased by 23•6% (P = .003), while the length of individual hospital stays (in days) increased 10•5% (P = .116). CONCLUSION: We report a reduction in the number of radiotherapy treatments and surgeries performed cancer carried out, ambulatory and emergency appointments, hospitalization and admission of new cases of cancer during peak of COVID-19 in an important public tertiary cancer center in the northeast region of Brazil.
Equity in oncology clinical trial participation has been declared a global priority. Australia is a key stakeholder in the global clinical trials sphere and managed to maintain high clinical trial activity during the COV...Equity in oncology clinical trial participation has been declared a global priority. Australia is a key stakeholder in the global clinical trials sphere and managed to maintain high clinical trial activity during the COVID pandemic. Despite these successes, there is paucity of understanding about what influences clinical trial participation in Australia. In the international context, systematic reviews have highlighted that sociodemographic barriers, access to health care, clinical trial inclusion criteria, and attitudes of physicians and patients are factors which influence oncology trial participation. Exploring the factors in Australian health services which influence trial participation is now of significant importance. The lack of clear evidence directly highlights a need to assess the factors that influence oncology trial participation in Australia. We call for review of existing data to identify future directions in Australia which will potentially give deeper insights for the international clinical trial community.
According to the literature, skin metastases affect 0.7%-10.4% of patients with malignant neoplasms of internal organs and may be 1 presentation of systemic spread of the cancer. Skin metastases may be the first sign of...According to the literature, skin metastases affect 0.7%-10.4% of patients with malignant neoplasms of internal organs and may be 1 presentation of systemic spread of the cancer. Skin metastases may be the first sign of relapse after treatment and about 30% of cases of skin metastases are diagnosed before the diagnosis of internal organ cancer. Cutaneous metastases most often come from breast cancer and melanoma. They can present synchronous or metachronous. Adequate vigilance, combined with knowledge of the clinical picture and epidemiology, can contribute to accurate diagnosis and treatment. Clinically, skin metastases occur in the form of atypical solitary, painless nodules, or tumors. Lumps or infiltrating foci do not show clinical features that help in making a diagnosis. Skin changes are more accessible during physical examination, and it is easier to do a biopsy and provide histological assessment. Dermoscopy, a useful initial tool for the assessment of skin metastases, can lead to a rapid accurate diagnosis and treatment. Ultimately, the diagnosis of a metastatic malignancy is confirmed by histopathological examination.
PURPOSE/OBJECTIVES: Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature...PURPOSE/OBJECTIVES: Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature search, summarized RRD features, and compared the most common drug classes implicated in this phenomenon. MATERIALS/METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane DBSR databases were queried through July 1, 2019 using key words: radiation recall, RRD, and radiodermatitis (limited to humans and English language). Studies included case reports in which patients treated with radiotherapy were initiated on a new line of systemic therapy and subsequently developed a skin reaction in the irradiated area. RRD cases were organized by whether RRD occurred after a single drug or multiple drug administration. RESULTS: One-hundred fifteen studies representing 129 RRD cases (96 single-drug RRD, 33 multi-drug) were included. Sixty-three drugs were associated with RRD. Docetaxel (22) and gemcitabine (18) were the two drugs most commonly associated with RRD. Breast cancer (69 cases) was the most commonly associated tumor type. For single-drug RRD, the median radiotherapy dose was 45.0 Gy (range, 30.0-63.2 Gy). The median time from radiotherapy to drug exposure, time from drug exposure to RRD and time to significant improvement was 8 weeks (range, 2-132 weeks), 5 days (range, 2-56 days), and 14 days (range, 7-49 days), respectively. Variables significantly associated with grade ≥2 toxicity were docetaxel (P = 0.04) and non-antifolate antimetabolite (P = 0.05). The only variable significantly associated with grade ≥3 toxicity was capecitabine (P = 0.04). CONCLUSIONS: RRD is a complex toxicity that can occur after a wide range of radiotherapy doses and many different systemic agents. Most commonly, it presents in patients diagnosed with breast cancer and after administration of a taxane or antimetabolite medication. RRD treatment generally consists of corticosteroids with consideration of antibiotics if superinfection is suspected. Drug re-challenge may be considered after RRD if the initial reaction was of mild intensity.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for almost 80%-85% of all lung cancer cases. Unfortunately, more than half of the patients will be diagnosed with advanced disease at t...Non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for almost 80%-85% of all lung cancer cases. Unfortunately, more than half of the patients will be diagnosed with advanced disease at the time of presentation, which makes their disease incurable. Historically, the 5 year overall survival for advanced NSCLC was 5%. However, there has been a significant increase in our understanding of the genetic basis of NSCLC, which has led to development of both immunotherapy and targeted therapy agents. This has improved the 5 year overall survival to become within the range of 15%-50% depending on certain mutations and biomarkers. Over the last decade the United States Food and Drug Administration (FDA) has approved almost 20 new targeted therapies and clinical trials are still undergoing to evaluate more novel agents. In this review, we will present recent updates on novel targeted therapies.
Drug-drug interactions (DDIs) with anticancer drugs are common and can significantly affect efficacy and toxicity of treatment. Therefore, a Dutch Multidisciplinary Expert group is assessing the clinical significance of...Drug-drug interactions (DDIs) with anticancer drugs are common and can significantly affect efficacy and toxicity of treatment. Therefore, a Dutch Multidisciplinary Expert group is assessing the clinical significance of DDIs in oncology and provides recommendations for the management of these DDIs. We present an overview of methodology and outcome of an evidence- and consensus-based assessment of DDIs between anticancer drugs and non-anticancer drugs. A literature search was performed through PubMed and EMA and FDA assessment reports, to identify potential DDI's involving anticancer drugs. For each potential DDI a concept report for risk analysis and practical advice for management was created. Subsequently, this risk analysis and the corresponding advice were assessed and weighed. A total of 290 potential DDIs have been identified in the literature thus far. Of these 290 potential DDIs, the Expert Group has identified 94 (32%) DDIs as clinically relevant, with a need for an automated alert and a suggested intervention. Furthermore, 110 DDIs have been identified as clinically not relevant. For 86 potential DDIs evidence supporting a relevant DDI was insufficient and in these cases neither an alert nor advice regarding a suggested intervention were formulated. A transparent risk analysis is presented for identification of clinically relevant DDIs with anticancer drugs. Integration of DDI guidelines into the national electronic prescribing system is essential to achieve optimal efficacy and minimal toxicity in patients receiving anticancer therapy. A clear overview of clinically relevant DDIs with anticancer therapy provides clinicians with a structured, evidence-based and consensus-built tool for anticancer therapy surveillance.
Individuals with germline E-cadherin (CDH1) mutations are at high risk of developing diffuse gastric cancer (GC) and prophylactic total gastrectomy (PTG) represents the only life-saving treatment. We reviewed all PTGs re...Individuals with germline E-cadherin (CDH1) mutations are at high risk of developing diffuse gastric cancer (GC) and prophylactic total gastrectomy (PTG) represents the only life-saving treatment. We reviewed all PTGs reported in literature associated with CDH1 germline mutations. A total of 224 PTGs were reported. The majority were described in the United States of America (50%), the Netherlands (17.8%), and Canada (12.5%). GC was identified in 85.4% of cases after PTG, with a high rate of "no cancer" at histopathology identified in the United States of America (19.6%). Considering the mutation type, a total of 61 different germline mutations was reported, primarily non-missense versus missense alterations (86.9% v 13.1%). Twenty-one PTGs were performed in individuals with no family history of GC, and tumor was detected in 33.3% of investigated cases; regarding individuals with a family history of GC, tumor was identified in 85% of cases. PTG remains the best treatment for individuals harboring germline CDH1 mutations and fulfilling specific clinical criteria; in other CDH1-associated conditions, PTG should be suggested, but not strongly recommended. Additional studies are required to assess the cancer risk in those conditions.
Lung cancer (both adenocarcinoma and squamous cell) progress through a series of pre-malignant histologic changes before the development of invasive disease. Each of these carcinogenic cascades is defined by genetic and...Lung cancer (both adenocarcinoma and squamous cell) progress through a series of pre-malignant histologic changes before the development of invasive disease. Each of these carcinogenic cascades is defined by genetic and epigenetic alterations in pulmonary epithelial cells. Additionally, alterations in the immune response, progenitor cell function, mutational burden, and microenvironmental mediated survival of mutated clones contribute to the risk of pre-malignant lesions progressing to cancer. Medical preventions studies have been completed and current and future trials are informed by the improved understanding of pre-malignancy. This will lead to precision chemoprevention trials based on lesional biology and histologic characteristics.
Immune check point inhibitors (ICI) have secured regulatory approvals across the world for the treatment of various types of cancers. Though not as frequent as immune-related adverse events (AEs) involving other organs,...Immune check point inhibitors (ICI) have secured regulatory approvals across the world for the treatment of various types of cancers. Though not as frequent as immune-related adverse events (AEs) involving other organs, a considerable number of ICI-related renal AE have also been reported and predicting such events has become important. We provide an updated review on possible mechanisms of ICI-related acute kidney injury (AKI), related risk factors, and the use of ICIs in patients with chronic kidney diseases (CKD). A systematic search for related articles was conducted. Acute tubulointerstitial nephritis (ATIN) is known to be the main cause of ICI-related AKI, with glomerulonephritis also a significant cause. Factors including use of concurrent medications, extra-renal immune related AEs, and combination of two or more immunotherapy drugs are possible risk factors. Use of ICI in patients with CKD may be related to increased occurrence of overall immune related AEs. If the diagnosis of ICI related renal AEs is confirmed, prompt use of steroids is recommended, and in severe cases of AKI, discontinuation of ICI should be considered.
Multiple myeloma (MM) is a plasma cell malignancy that accounts for approximately a tenth of all blood cancers. The last two decades, have witnessed considerable improvement in survival rates driven by a better understan...Multiple myeloma (MM) is a plasma cell malignancy that accounts for approximately a tenth of all blood cancers. The last two decades, have witnessed considerable improvement in survival rates driven by a better understanding of the biology of MM and the development of novel therapies to treat MM. Despite these advancements, MM remains an incurable disease. Marked disparities exist by race and ethnicity for MM, particularly a higher incidence and an earlier age of onset of MM among Non-Hispanic Black and Hispanic and Latinx individuals compared to Non-Hispanic Whites. Inequities in receipt and time to utilization of novel therapies and stem cell transplantation as well as participation in clinical trials have also been observed for Non-Hispanic Black and Hispanic and Latinx patients with a diagnosis of MM compared to Non-Hispanic White patients, yet Non-Hispanic Black patients have slightly better survival rates compared to Non-Hispanic White and Hispanic patients with MM. Most of the ongoing work to characterize and elucidate causes of these racial and ethnic disparities in MM etiology, outcomes, and treatment response compares Black and Non-Hispanic White individuals, with the Hispanic and Latinx population vastly understudied. Here, we provide an overview of the current state of knowledge on racial and ethnic differences in the epidemiology, biology, and clinical outcomes of patients with MM, with a special emphasis on Hispanic and Latinx individuals. We additionally discuss potential opportunities to consider for disparities research that includes Hispanic and Latinx patients with MM. Despite the encouraging progress in the study of health disparities in MM thus far, our review highlights the critical gaps that still remain to better understand MM in diverse populations and to develop more effective tools and approaches to provide all patients diagnosed with MM meaningful and transformative care.
Semin Oncol
· 2022 Feb · PMID 35197198
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As is the case for solid tumors, treatment paradigms have shifted from non-specific chemotherapeutic agents towards novel targeted drugs in the treatment of patients with multiple myeloma (MM). Currently, multiple target...As is the case for solid tumors, treatment paradigms have shifted from non-specific chemotherapeutic agents towards novel targeted drugs in the treatment of patients with multiple myeloma (MM). Currently, multiple targeted therapies are available to treat patients augmenting the arsenal of modalities which also includes chemotherapy, immunotherapy, radiation therapy, hematopoietic stem cell transplantation (HSCST) and chimeric antigen T-cell therapy (CAR-T). These novel, targeted agents have dramatically increased optimism for patients, who may now be treated over many years with successive regimens. As fortunate as we are to have these new therapies available for our patients, this advantage is juxtaposed with the challenges involved with delivering them safely. While each class of agents has demonstrated efficacy, in terms of response rates and survival, they also exert class effects which pose risks for toxicity. In addition, newer generation agents within the classes often have slightly different toxicity profiles than did their predecessors. These factors must be addressed, and their risks mitigated by the multidisciplinary team. This review presents a summary of the evolution of drug development for MM. For each targeted agent, the efficacy data from pivotal trials and highlights of the risks that were demonstrated in trials, as well as during post-marketing surveillance, are presented. Specific risks associated with agents within the classes, that are not shared with all new class members, are described. A table presenting these potential risks, with recommended nursing actions to mitigate toxicity, is provided as a quick reference that nurses may use during the planning, and provision, of patient care.
Semin Oncol
· 2022 Feb · PMID 35190200
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Imaging innovations offer useful techniques applicable to many oncology specialties. Treatment advances in the field of multiple myeloma (MM) have increased the need for accurate diagnosis, particularly in the bone marro...Imaging innovations offer useful techniques applicable to many oncology specialties. Treatment advances in the field of multiple myeloma (MM) have increased the need for accurate diagnosis, particularly in the bone marrow, which is an essential component in myeloma-defining criteria. Modern imaging identifies osteolytic lesions, distinguishes solitary plasmacytoma from MM, and evaluates the presence of extramedullary disease. Furthermore, imaging is increasingly valuable in post-treatment response assessment. Detection of minimal residual disease after therapy carries prognostic implications and influences subsequent treatment planning. Whole-body low-dose Computed Tomography is now recommended over the conventional skeletal survey, and more sophisticated functional imaging methods, such as F-Fluorodeoxyglucose Positron Emission Tomography , and diffusion-weighted Magnetic Resonance Imaging are proving effective in the assessment and monitoring of MM disease. This review focuses on understanding indications and advantages of these imaging modalities for diagnosing and managing myeloma.
Daratumumab, a human IgG1 kappa monoclonal antibody targeting CD38 has transformed the treatment paradigm of multiple myeloma (MM). With the identification of CD38 as a crucial receptor involved in immune system function...Daratumumab, a human IgG1 kappa monoclonal antibody targeting CD38 has transformed the treatment paradigm of multiple myeloma (MM). With the identification of CD38 as a crucial receptor involved in immune system function, it became an ideal target for monoclonal antibody (mAb) drug development in MM. Daratumumab's unique multifaceted mechanism of action has led to great success in the treatment of relapsed refractory multiple myeloma (RRMM) as well as newly diagnosed multiple myeloma (NDMM) patients. Along with its efficacy comes a low toxicity profile, improved further with the introduction of subcutaneous daratumumab. With such success within MM, daratumumab is now being explored in other disease states. This article will review daratumumab's drug development, practical use, and future potential indications.
Chojnacka M, Diamond B, Landgren O
… +1 more, Maura F
Semin Oncol
· 2022 Feb · PMID 35168813
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All patients with a diagnosis of multiple myeloma (MM) have a preceding, asymptomatic expansion of clonal plasma cells, clinically recognized as monoclonal gammopathy of undetermined significance or smoldering multiple m...All patients with a diagnosis of multiple myeloma (MM) have a preceding, asymptomatic expansion of clonal plasma cells, clinically recognized as monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (SMM). While most patients with monoclonal gammopathy of undetermined significance have a very small rate of progression, SMM is a widely heterogeneous condition where a fraction of patients will progress to symptomatic MM rather quickly, while others will experience an indolent clinical course. The differentiation between progressive and stable precursor condition thus represents one of the most important unmet clinical needs in the MM community. The ability to identify patients at high-risk of progression before major clonal expansion and onset of end-organ damage would enable strategies for early prevention and perhaps more effective intervention. All proposed criteria to predict the progression of myeloma precursor conditions are built around indirect markers of disease burden and, therefore, are generally able to accurately identify only a small fraction of patients in whom progression to MM is already occurring. Leveraging whole genome and exome sequencing, it has been shown that patients with stable myeloma precursor conditions are characterized by either absence or lower prevalence of distinct genomic events that are detectable in progressive precursor condition years before the progression. In this review, we discuss evolving genomic concepts and tools; and their ability to differentiate myeloma precursor conditions into two distinct entities: one benign (monoclonal gammopathy of benign significance) and another malignant (asymptomatic multiple myeloma).
Multiple myeloma (MM) is a complex hematological malignancy. Advances in therapy over the last decade have resulted in significant improvement in overall survival for patients with a diagnosis of MM, leading to a substan...Multiple myeloma (MM) is a complex hematological malignancy. Advances in therapy over the last decade have resulted in significant improvement in overall survival for patients with a diagnosis of MM, leading to a substantial number of older people living with the disease. However, patients continue to suffer from a multitude of debilitating symptoms that can significantly affect their quality of life, a problem that especially can impact patients with MM considered in the geriatric age group. In the first part of our review, we reflect on traditional measurement tools that are used to assess health related quality of life in patients living with MM, as they undergo different types of treatment regimens. In the second part, we discuss the potential role of the Internet of Medical Things in tracking and actively enhancing health related quality of life in patients with a diagnosis of MM. We conceptualize models of passive and active digital health technology platforms that are posed to transform the patient-physician relationship in the new era of advanced care.
Semin Oncol
· 2022 Feb · PMID 35125242
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Multiple myeloma is a common hematological malignancy of plasma cells, the terminally differentiated B cells that secrete antibodies as part of the adaptive immune response. Significant progress has been made in treating...Multiple myeloma is a common hematological malignancy of plasma cells, the terminally differentiated B cells that secrete antibodies as part of the adaptive immune response. Significant progress has been made in treating multiple myeloma, but this disease remains largely incurable, and most patients will eventually suffer a relapse of disease that becomes refractory to further therapies. Moreover, a portion of patients with multiple myeloma present with disease that is refractory to all treatments from the initial diagnosis, and no current therapeutic approaches can help. Therefore, the task remains to advance new therapeutic strategies to help these vulnerable patients. One strategy to meet this challenge is to unravel the complex web of pathogenic signaling pathways in malignant plasma cells and use this information to design novel precision medicine strategies to assist these patients most at risk.
Multiple myeloma (MM) is hematologic malignancy that is associated with profound immune alterations. Myeloma cells are susceptible to killing by natural killer (NK) cells but acquire the ability to elude NK cell surveill...Multiple myeloma (MM) is hematologic malignancy that is associated with profound immune alterations. Myeloma cells are susceptible to killing by natural killer (NK) cells but acquire the ability to elude NK cell surveillance by avoiding recognition and suppressing NK cell function. Major advances in the treatment of multiple myeloma have been achieved by effective new drugs that redirect NK cells and enhance their function. Despite significant progress, myeloma remains incurable and novel treatment approaches are required. Strategies to take advantage of the intrinsic antitumor properties of NK cells to treat MM represent a novel immunotherapeutic approach. One such strategy is adoptive NK cell therapy that consist of infusions of NK cells that have been propagated ex vivo. Adoptive NK cell therapy encompasses contemporary genetic engineering strategies such as chimeric antigen receptor (CAR)-engineered NK cells. An alternative approach involves the use of pharmacologic agents to enhance NK cell activity against myeloma. NK cell-modulating therapies can be used to bolster the function of endogenous NK cells or to enhance the efficacy of adoptively infused NK cells. Here, we review the mechanistic complexities influencing NK cell activity in MM and highlight a variety of innovative NK cell-based strategies being developed for the treatment of MM.