Edward R Scheffer Cliff

Edward R Scheffer Cliff
Brigham and Women's Hospital | BWH · Department of Medicine

MBBS (Hons) BMedSc (Hons) MPH

About

84
Publications
4,883
Reads
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451
Citations
Additional affiliations
August 2022 - present
Harvard Medical School
Position
  • Postdoctoral Research Fellow

Publications

Publications (84)
Article
@Eddie_Cliff et al explore the scientific & ethical reasons why patients randomized to the control arm of trials should 'crossover' to receive the investigational therapy if their disease progresses
Article
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Chimeric antigen receptor (CAR) T-cells are a cellular immunotherapy with remarkable efficacy in treating multiple hematologic malignancies but they are associated with extremely high prices that are, for many countries, prohibitively expensive. As their use increases both for hematologic malignancies and other indications, and large numbers of new...
Article
Importance The US Food and Drug Administration’s (FDA) accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered “reasonably likely” to predict clinical benefit. Postapproval clinical trials are then required to confirm whether these drugs offer clinical bene...
Article
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Although chimeric antigen receptor (CAR) T cell therapy represents a transformative immunotherapy, it is also associated with distinct toxicities that contribute to morbidity and mortality. In this systematic review and meta-analysis, we searched MEDLINE, Embase and CINAHL (Cochrane) for reports of nonrelapse mortality (NRM) after CAR T cell therap...
Article
This Viewpoint discusses the high cost of new gene therapies for sickle cell disease, the challenges these costs pose for health care access, and new policy approaches to ensure fair reimbursement for payers and manufacturers without further increasing health care costs or barriers to access for underserved populations.
Article
The isocitrate dehydrogenase (IDH) inhibitor, vorasidenib, may offer a promising new treatment option for patients with IDH-mutant gliomas. However, the indefinite nature of this targeted therapy raises significant financial concerns. High costs of targeted cancer therapies, often exceeding $150 000 annually, contribute to financial toxicity, chara...
Article
This Viewpoint describes considerations for regulatory oversight in the implementation of artificial intelligence–enabled prognostic devices.
Article
Importance Limited availability and affordability of cancer drugs contribute to staggering disparities in cancer survival between high-income and low- and middle-income countries (LMICs). As infrastructure for cancer care rapidly develops, there is an urgent need to reduce prices and improve access to cancer medicines in LMICs to advance pharmacoeq...
Article
Introduction CAR T-cells represent a major treatment advance for certain patients with hematologic malignancies. Barriers to accessing this technology include its prohibitive cost, the autologous nature of CAR T-cells (which necessitates a delay between apheresis and infusion), and the need for a specialized manufacturing process requiring a sophis...
Article
Introduction: The advent of many novel myeloma treatments has increased the complexity of decision making for doctors and patients. Multiple available treatment options (some longstanding and others newly approved) lead to improved surrogate outcomes such as progression-free survival (PFS) but have not been shown to extend overall survival (OS). To...
Article
Introduction: Although not formally approved for the treatment of multiple myeloma (MM), the BCL2 inhibitor venetoclax (ven) has shown promising activity in patients (pts) with MM whose disease harbors t(11;14). The randomized BELLINI trial (VenVd vs Vd in unselected MM pts, Kumar Lancet Oncol 2020) demonstrated improved PFS, especially in the 35 p...
Article
Introduction Despite its advantages, 18F FDG positron emission tomography (PET) can yield false positives in diffuse large B cell lymphoma (DLBCL), potentially putting patients at risk of overtreatment. This was seen in long-term follow-up of the GOYA trial, where >50% of patients who did not achieve complete remission on end of treatment (EOT) PET...
Article
Overview Chimeric Antigen Receptor (CAR) T-cells are an effective treatment for a variety of hematologic malignancies, received by >30,000 patients to date. Autologous T-cells are genetically modified ex-vivo using lenti- or retro-viral transduction to express a CAR receptor, which confers T-cells with HLA-independent tumor antigen recognition and...
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Background: Polatuzumab vedotin (Pola) is an antibody drug conjugate targeting CD79b that incorporates the microtubule disrupting monomethyl auristatin E payload. Pola was approved in 2023 for the upfront treatment of diffuse large B cell lymphoma (DLBCL) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (polaRCHP) based...
Article
Patients with certain subsets of multiple myeloma continue to have poor outcomes and are in need of novel treatment approaches. Strict eligibility criteria for randomized controlled trials (RCTs) limit access to clinical trials and limit the external validity of trial results for these patients. We systematically reviewed RCTs in newly diagnosed my...
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Purpose Chimeric antigen receptor (CAR) T-cell therapy is a potent immunotherapy for hematologic malignancies, but patients can develop long-term adverse events, including second primary malignancies (SPM) that impact morbidity and mortality. To delineate the frequency and subtypes of SPMs following CAR-T in lymphoma and myeloma, we performed a sys...
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Background Smoldering multiple myeloma (SMM), an asymptomatic precursor of multiple myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM. We compared the efficacy of treatment regimens studie...
Article
Platypnoea–orthodeoxia is a rare clinical syndrome characterised by dyspnoea and oxygen desaturation in the upright position which improves when supine. It requires two components: a sufficiently sized anatomical vascular defect (typically intra‐cardiac or intra‐pulmonary) combined with a functional component that promotes positional right‐to‐left...
Article
Once a promising new cancer therapy emerges, other manufacturers often develop drugs with the same molecular target. Some follow on drugs offer meaningful benefit via improved efficacy or reduced toxicity, but others offer minimal benefit. We hypothesized there are two cohorts of follow on drugs: those developed concurrently before efficacy & safet...
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Background Prior systematic reviews addressing the impact of diet on cancer outcomes have focused on specific dietary interventions. In this systematic review, we assessed all RCTs investigating dietary interventions for cancer patients, examining the range of interventions, endpoints, patient populations, and results. Methods This systematic revi...
Preprint
Full-text available
While CAR-T therapy represents a transformative immunotherapy, it is also associated with distinct toxicities that contribute to morbidity and mortality. In this systematic review and meta-analysis, we searched MEDLINE, Embase and CINAHL for reports of non-relapse mortality (NRM) following CAR-T in lymphoma and myeloma, published until 09/2023. Cum...
Article
Full-text available
18F- fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valuable prognostic tool in modern lymphoma care. In this study, we explored the utility of quantitative FDG-PET parameters in predicting the histology of suspected relapsed/refractory (R/R) lymphoma. We retrospectively analyzed 290 FDG-PET scans performed for suspected R/R lymphom...
Article
Background: First-line treatment of diffuse large B-cell lym-phoma (DLBCL) achieves durable remission in approximately60% of patients. In relapsed or refractory disease, only about20% achieve durable remission with salvage chemoimmuno-therapy and consolidative autologous stem cell transplantation(ASCT). The ZUMA-7 (axicabtagene ciloleucel [axi-cel]...
Article
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Introduction: SMM is an asymptomatic precursor of multiple myeloma (MM), affecting ~1 in 200 people aged >40 years. Historically, risk of progression from SMM to MM was 10% per year in the first 5 years. However, since then, the definition and characteristics of the SMM patient population have changed substantially. First, IMWG diagnostic criteria...
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Introduction: Patients with the most aggressive, hardest-to-treat, and rarer forms of multiple myeloma (MM), such as patients with severe renal impairment, central nervous system (CNS) disease, extramedullary disease, and plasma cell leukemia, have the greatest need of novel therapeutic approaches. Strict eligibility criteria for randomized control...
Article
Introduction: The advent of podcasts has revolutionized the field of medical education. Podcasts offer a portable and convenient format that accommodates the busy schedule of healthcare professionals and students alike. Initially popularized particularly in the field of critical care medicine and emergency medicine (Cadogan M et.al 2014), education...
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Multiple myeloma is a plasma cell malignancy that, while typically incurable, is now associated with a median life-expectancy of 8-10 years. Myeloma tends to affect older patients, with a prevalence of 0.2% among Medicare beneficiaries. Patients often receive treatment continuously over several years, and guidelines recommend triplet (or quadruplet...
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BACKGROUND Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of subgroup analysis. METHODS We systematically reviewed publishe...
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Importance Cancer treatment can result in burdensome toxic effects that profoundly affect patient quality of life. In seeking to emphasize the efficacy of tested treatments, clinical trial reports may use subjective or minimizing terms to describe adverse events (AEs). Objective To evaluate patterns of AE reporting in multiple myeloma (MM) randomi...
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Importance Many cancer drugs are approved under the US Food and Drug Administration (FDA) accelerated approval pathway based on preliminary evidence. It is unclear how this limited evidence is integrated into the National Comprehensive Cancer Network (NCCN) guidelines, which are common references for clinicians and are used by public and private pa...
Article
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Background Smoldering myeloma (SMM) is an asymptomatic precursor condition to multiple myeloma (MM) with a variable risk of progression. The management of high-risk SMM (HR-SMM) remains controversial, particularly with changes in diagnostic criteria that led to reclassifying of some patients with SMM to MM. This study aimed to assess clinician pref...
Article
Subgroup analysis from the POLARIX trial of polatuzumab vedotin plus chemotherapy for untreated large B-cell lymphoma suggests greater efficacy among patients with activated B-cell subtype disease. Both preclinical and additional clinical evidence support this interaction between cell-of-origin and polatuzumab efficacy.
Article
Cytarabine-containing chemoimmunotherapy followed by autologous transplantation and rituximab maintenance achieves durable remissions for most patients with mantle cell lymphoma (MCL). However, patients with TP53-mutated disease have poor outcomes with standard approaches. We previously reported that allogeneic stem cell transplantation (alloSCT) a...
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Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein–coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some exten...
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1599 Background: Many oncology drugs are approved via FDA’s accelerated approval pathway based on trials showing changes to surrogate measures only ‘reasonably likely’ to predict clinical benefit. Despite this preliminary evidence, accelerated approval drugs are incorporated into clinical practice and included in guidelines. We assessed NCCN eviden...
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This cross-sectional study analyzes trends in Medicare Part D use and spending on oral-targeted drugs for chronic lymphocytic leukemia from 2014 to 2020.
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Invasive fungal infections (IFI) are challenging to predict, diagnose and treat, and are associated with a particularly high mortality among patients with hematological malignancies. They are relatively uncommon in patients with lymphoma, compared with those with acute leukemia or undergoing allogeneic transplantation. We present a patient, autogra...
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In this perspective, we highlight both the promise and harms of screening for plasma cell dyscrasias, as well as the implications of the use of mass spectrometry for diagnosing monoclonal gammopathy of undetermined significance in routine practice.
Article
Median overall survival for patients with newly diagnosed multiple myeloma may surpass ten years. Nonetheless, many patients face considerable treatment-related morbidity and relapsed disease. Owing to this typically long overall survival, most multiple myeloma trials now use progression-free survival as their primary end point. In this Comment, we...
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In the POLARIX trial, pola‐R‐CHP demonstrated improved progression‐free survival (PFS) compared to R‐CHOP in untreated intermediate‐ to high‐risk DLBCL. We surveyed practicing clinicians regarding their interpretation of POLARIX, including impressions of efficacy, safety, and cost. Of 174 respondents, most from academic centers (82%) in the United...
Article
7537 Background: The recently reported ZUMA-7 and TRANSFORM trials demonstrate superior event-free survival among patients with primary refractory or early relapsed DLBCL compared to salvage chemotherapy with ASCT. However, given a cost of >$370,000, it is not known whether second-line CAR-T is cost-effective compared to ASCT. Thus, we developed a...
Article
Dealing with cancer, and making decisions about treatment, is hard enough in its own right, harshly compounded by the immense loneliness enforced by banning visitors from our wards. As we try to protect the most vulnerable in our community from the pandemic, I just hope that we are not losing sight of our humanity and compassion along the way.
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Background: Langerhans Cell Histiocytosis (LCH) is a rare inflammatory neoplasm originating from bone marrow-derived CD207+/CD1+ clonal dendritic cells, with cells expressing BRAF V600E in around 50% of cases. Although more common in the paediatric setting, LCH is rare in adults, with an incidence of 1 to 2 cases per million. This combination of di...
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Covalent Bruton tyrosine kinase inhibitors (BTKis) and the BCL2 inhibitor venetoclax have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL), especially those with biologically adverse disease. Patients with CLL resistant to their first targeted agent (TA) can be effectively treated with the alternative class. Howe...
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Objective: Denosumab is often used in men with advanced prostate cancer to prevent skeletal related events, but can be associated with severe hypocalcaemia. Our objective was to review the pathophysiology, identify risk factors and provide recommendations for prevention and management of denosumab-associated hypocalcaemia. Design: We reviewed th...
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Background Permanent neonatal diabetes caused by mutations in the KCNJ11 gene may be managed with high‐dose sulfonylureas. Complete transfer to sulfonylureas is not successful in all cases and can result in insulin monotherapy. In such cases, the outcomes of combining sulfonylureas with insulin have not been fully explored. We present the case of a...
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There is an oversupply of Australian junior doctors, but significant training bottlenecks are developing, and geographical maldistribution in rural and remote areas remains. Last year, the Federal Minister for Immigration rejected a Department of Health recommendation for the removal of 41 health roles from the Skilled Occupation List after concern...
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Aims/hypothesis: The pancreatic ATP-sensitive potassium (KATP) channel plays a pivotal role in linking beta cell metabolism to insulin secretion. Mutations in KATP channel genes can result in hypo- or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, respectively. To date, all patients affected by neonatal...

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