Publications by authors named "Raza Shahzad"

Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare.

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Article Synopsis
  • CAR T-cell therapy shows strong initial results for treating relapsed refractory multiple myeloma, but most patients eventually relapse, often within 5 months.
  • In a study of 139 patients who relapsed after CAR T-cell therapy, different salvage therapies were analyzed, revealing that bispecific antibodies, like talquetamab and teclistamab, had the best overall and complete response rates.
  • The presence of extramedullary disease at relapse was linked to poorer outcomes, but bispecific antibodies improved survival rates, suggesting they should be the standard treatment for patients relapsing after CAR T-cell therapy.
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Multiple myeloma (MM) is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight the integration of monoclonal antibodies, particularly CD38 recombinant monoclonal antibody agents, into treatment regimens.

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The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen.

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Multiple myeloma is a heterogeneous condition characterized by the proliferation of monoclonal B-cells, for which there is currently no curative treatment available. Relapses are, unfortunately, common after first-line treatment. While the prognosis for relapsed refractory multiple myeloma is generally poor, advances in the treatment of relapsed or refractory multiple myeloma offer hope.

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  • Daratumumab treatment for light chain (AL) amyloidosis can lead to early refractoriness, leaving patients with fewer options if they relapse or respond poorly.
  • This study assessed the effectiveness of venetoclax therapy in AL patients with t(11;14) who had previously failed daratumumab, involving 31 subjects.
  • Results showed a 97% overall hematologic response to venetoclax, with strong organ responses in patients with cardiac (74%) and renal (46%) involvement, indicating promising potential for venetoclax as a salvage therapy after daratumumab failure.
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  • Multiple myeloma (MM) is a cancer of the plasma cells in the bone marrow that leads to symptoms like anemia, renal issues, and fatigue, but currently available treatments often have limited long-term success and frequent relapses occur.* -
  • The development of drug resistance in myeloma cells complicates treatment, making ongoing research into new therapeutic targets and strategies essential for improving patient outcomes.* -
  • This article reviews new and emerging treatment options for MM, organized by specific molecular targets like BCMA and CD38, as well as treatments such as immunomodulatory drugs and NK cell therapy.*
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Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell-directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi-institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy.

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BCMA-directed chimeric antigen receptor T-cell (CAR T) therapies, including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have transformed the treatment landscape for relapsed-refractory multiple myeloma (RRMM), offering remarkable efficacy with hallmark toxicity risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The FDA mandates a 4-week monitoring period at the treatment center as part of a Risk Evaluation and Mitigation Strategy (REMS) to monitor and manage these toxicities, which, while prudent, may add unnecessary challenges related to access and socioeconomic disparities. We sought to assess CRS and ICANS onset and duration, as well as causes of non-relapse mortality (NRM) in real-world BCMA CAR T recipients in order to better inform future changes to the monitoring guidelines for CAR T recipients.

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Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.

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Article Synopsis
  • * A total of 19 studies were analyzed, highlighting promising results with drugs like tafamadis and RNA interference treatments that improve quality of life for patients, especially when treatments start early.
  • * Despite the potential of multiple therapies, significant gaps remain in long-term outcomes and their economic implications, indicating a need for further research and exploration in this field.
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The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T.

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  • - Light chain amyloidosis is a serious plasma-cell disorder that leads to severe organ damage and poor prognosis, causing significant pain and disability for patients.
  • - Treatment is complicated and includes chemotherapy, pain management, and addressing symptoms, necessitating clear communication about goals and limitations of therapy for patients and families.
  • - Integrating palliative care can enhance the quality of life for patients, reduce healthcare costs, and minimize hospital visits, emphasizing the importance of comprehensive support in managing AL amyloidosis.
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  • - AL amyloidosis is a condition caused by the overproduction of faulty immunoglobulins, leading to harmful amyloid fibrils that primarily affect the heart and kidneys, with symptoms like fatigue and weight loss often causing delayed diagnosis.
  • - The Pavia renal staging model helps predict the need for dialysis, and the combination treatment of daratumumab with cyclophosphamide, bortezomib, and dexamethasone has shown effectiveness in improving kidney function and reducing early mortality in patients, as seen in the ANDROMEDA trial.
  • - Challenges remain in treating relapsed cases due to individual patient differences, but promising indicators like the t(11:14) genetic change may enhance responses to certain therapies,
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Introduction: Pharmacovigilance plays a pivotal role in monitoring adverse events (AEs) related to chemical substances in human/animal populations. With increasing spontaneous-reporting systems, researchers turned to approaches to efficiently analyze drug safety profiles. Here, we review methods employed for assessing multiple drug-drug/drug-disease AEs covered by comparative analyses and visualization strategies.

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Ide-cel received approval for relapsed-refractory multiple myeloma based on the results of the KarMMa-1 trial. However, patients with significant comorbidities, aggressive disease and prior B-cell maturation antigen-directed therapy (BCMA-DT) were excluded. This retrospective study evaluated real-world outcomes of patients who did not meet the KarMMa-1 eligibility criteria and were treated with standard of care (SOC) ide-cel.

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Article Synopsis
  • Teclistamab, a bispecific antibody targeting B cell maturation antigen, shows promising efficacy in treating relapsed/refractory multiple myeloma (RRMM) based on the real-world outcomes of 106 patients, most of whom would have been ineligible for clinical trials.
  • The overall response rate (ORR) was 66%, with a complete or better response rate of 29%, and the median progression-free survival (PFS) was 5.4 months.
  • Adverse events included cytokine release syndrome in 64% of patients and infections in 31%, with a focus on specific patient factors like age and baseline health status affecting outcomes.
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Immunotactoid deposition is a rare fibrillary deposition disease that is primarily seen in the kidney and is associated with paraproteinemia. Here, we report a case of hepatic immunotactoid deposition in a 67-year-old male with a history of smoldering myeloma and chronic kidney disease who underwent liver transplantation for metabolic dysfunction-related cirrhosis. Immunotactoid deposition was first identified in the explanted liver and recurred in the allograft within only 7 weeks following transplantation, presenting as ascites with normal liver function tests.

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The literature is limited regarding outcomes in older adults and frail patients receiving BCMA-directed chimeric antigen receptor T cell therapy (CAR-T) for relapsed or refractory multiple myeloma. Here we describe the safety and efficacy of CAR-T in these clinically important subgroups treated in a real-world setting. Frailty was defined as a frail score ≥2 using the simplified frailty index (score based on age + Eastern Cooperative Oncology Group [ECOG] Performance Status + Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI]).

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Brain metastasis in gastric cancer (GC) patients is a rare phenomenon that is associated with adverse clinical outcomes and poor survival rates. We conducted a retrospective cohort study to investigate the incidence, risk factors and prognostic factors of brain metastasis in GC patients. Data on sociodemographic and tumor characteristics of GC patients from 2010 to 2019 was extracted from the Surveillance, Epidemiology and End-Results (SEER) database.

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Background: Pain is the most prevalent symptom in cancer patients. To improve pain care, World Health Organization (WHO) Pain ladder was introduced in 1986 as a template for choosing pain medications in oncological settings. Since then, advancements in oncological treatments have improved the survival of cancer patients, requiring prolonged analgesia in various treatment stages.

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Anti-B-cell maturation antigen therapies consisting of bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells have shown promising results in relapsed refractory multiple myeloma (RRMM). However, the severe side effects include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia(s), infections, hemophagocytic lymphohistiocytosis, and organ toxicity, which could sometimes be life-threatening. This review focuses on these most common complications post-BCMA therapy.

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Background: Patients with plasma cell dyscrasia are at a higher risk of developing a severe Coronavirus-2019 (COVID-19) infection. Here we present a systematic review of clinical studies focusing on the immune response to the COVID-19 vaccination in patients with plasma cell dyscrasia.

Objectives: This study aims to evaluate the immune response to COVID-19 vaccines in patients with plasma cell dyscrasia and to utilize the results to improve day-to-day practice.

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Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS) is a serious, uncommon disease that occurs in patients who are positive for HIV and human herpesvirus-8 (HHV-8). It is characterized by a constellation of clinical findings, including fever, weight loss, and fluid retention, as well as a lack of multicentric Castleman disease (MCD) features on histopathology and an elevated serum HHV-8 viral load. Diagnosis is often delayed, and treatment options are limited, culminating in high mortality rates.

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