Evaluating ChatGPT as an educational resource for patients with multiple myeloma: A preliminary investigation.

The findings of this study highlight a 95% accuracy rate in ChatGPT responses, as assessed by five myeloma specialists, underscoring its potential as a reliable educational tool.

Secondary Pure Red Cell Aplasia During Daratumumab/ Hyaluronidase Therapy for Multiple Myeloma.

Predominantly autoimmune in origin, severe normochromic, normocytic anemia with reticulocytopenia in the setting of the normal production of leukocytes and megakaryocytic lineages is known as pure red cell aplasia (PRCA), which is unlike aplastic anemia in which all lineages are affected due to a stem cell defect. PRCA can be primary (such as autoimmune) or acquired, which can be an acute self-limited illness or a chronic disease that may be induced by medications, including immunotherapy such as monoclonal antibodies (mAbs). Daratumumab is a mAb directed against CD38 used for the treatment of multiple myeloma and systemic amyloid light-chain amyloidosis. The intravenous formulation of daratumumab received initial FDA approval, and later approval was received for the subcutaneous formulation daratumumab and hyaluronidase-fihj. The subcutaneous version increases patient convenience and has become the preferred route of administration since its approval. We herein present the case of a patient with multiple myeloma who developed acquired DNMT3A-positive PRCA while transitioning to daratumumab/hyaluronidase after initial treatment with daratumumab.

How we treat systemic light-chain amyloidosis.

Systemic light-chain (AL) amyloidosis is a multisystem disease characterized by organ toxicity and damage due to monoclonal free light chains, which are produced by a neoplastic clone of plasma cells in bone marrow. Current treatment strategies target the clone in order to decrease the production of the pathologic light chains and thereby stop or reverse organ toxicity and damage. AL amyloidosis remains a formidable and often incurable disease despite treatment options that include corticosteroids, cytotoxic chemotherapy, risk-adapted melphalan, autologous hematopoietic stem cell transplantation, proteasome inhibitors, and immunomodulatory drugs. New and effective treatment approaches that can reverse the organ damage are urgently needed. Physicians and clinical staff should be aware of the importance of providing best supportive care to patients with advanced AL-related organ dysfunction, given the patients' often tenuous hemodynamics and fragile functional status. Organ transplantation has a role in selected clinical situations, and the treating hematologist should be aware of this sometimes-useful option.

Is S-1 a potential game changer in adjuvant therapy of pancreatic cancer?

There remains a lack of consensus on the optimal adjuvant therapy for pancreatic cancer. In general, chemoradiation is favored in the United States and gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free survivals and in some studies overall survival. We present the summary of three abstracts from the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting and discuss their potential impact on our clinical practice. Adjuvant oral chemotherapy with S-1 (Fukutomi et al., Abstract #4008) has now emerged as a promising alternative to the traditional gold standard of intravenous gemcitabine in a relatively large randomized phase III clinical trial. Another study by Yoshitomi et al. (Abstract #4056) examined the value of adjuvant chemotherapy with S-1 alone versus combination of S-1 and gemcitabine versus gemcitabine alone in a three arm phase II clinical trial (CAP-002 Study). In terms of biomarkers in pancreatic cancer, Neoptolemos et al. presented the impact of hENT1 tumor levels on the outcome of the patients with pancreatic cancer (Abstract #4006) who had received adjuvant chemotherapy with either 5-flurouracil or gemcitabine in the ESPAC trial.

Adjuvant therapy of pancreatic cancer.

There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium, the randomized phase III study presented by Uesaka et al. from Japan (Abstract #145) represents a newer paradigm of oral adjuvant S-1 chemotherapy in place of the traditional standard of care intravenous gemcitabine in terms of prolonging patients' survival. Another study by Fan et al. (Abstract #269) examined the value of targeted therapy using erlotinib with adjuvant chemoradiation and chemotherapy. We present the summary of these two studies and discuss the potential impact on our clinical practice on this highly lethal cancer.

Liquid biopsies and minimal residual disease in myeloid malignancies.

Minimal residual disease (MRD) assessment through blood component sampling by liquid biopsies (LBs) is increasingly being investigated in myeloid malignancies. Blood components then undergo molecular analysis by flow cytometry or sequencing techniques and can be used as a powerful tool for prognostic and predictive purposes in myeloid malignancies. There is evidence and more is evolving about the quantification and identification of cell-based and gene-based biomarkers in myeloid malignancies to monitor treatment response. MRD based acute myeloid leukemia protocol and clinical trials are currently incorporating LB testing and preliminary results are encouraging for potential widespread use in clinic in the near future. MRD monitoring using LBs are not standard in myelodysplastic syndrome (MDS) but this is an area of active investigation. In the future, LBs can replace more invasive techniques such as bone marrow biopsies. However, the routine clinical application of these markers continues to be an issue due to lack of standardization and limited number of studies investigating their specificities. Integrating artificial intelligence (AI) could help simplify the complex interpretation of molecular testing and reduce errors related to operator dependency. Though the field is rapidly evolving, the applicability of MRD testing using LB is mostly limited to research setting at this time due to the need for validation, regulatory approval, payer coverage, and cost issues. This review focuses on the types of biomarkers, most recent research exploring MRD and LB in myeloid malignancies, ongoing clinical trials, and the future of LB in the setting of AI.

Systemic AL amyloidosis: current approach and future direction.

Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.

Liquid biopsies and minimal residual disease in lymphoid malignancies.

Minimal residual disease (MRD) assessment using peripheral blood instead of bone marrow aspirate/biopsy specimen or the biopsy of the cancerous infiltrated by lymphoid malignancies is an emerging technique with enormous interest of research and technological innovation at the current time. In some lymphoid malignancies (particularly ALL), Studies have shown that MRD monitoring of the peripheral blood may be an adequate alternative to frequent BM aspirations. However, additional studies investigating the biology of liquid biopsies in ALL and its potential as an MRD marker in larger patient cohorts in treatment protocols are warranted. Despite the promising data, there are still limitations in liquid biopsies in lymphoid malignancies, such as standardization of the sample collection and processing, determination of timing and duration for liquid biopsy analysis, and definition of the biological characteristics and specificity of the techniques evaluated such as flow cytometry, molecular techniques, and next generation sequencies. The use of liquid biopsy for detection of minimal residual disease in T-cell lymphoma is still experimental but it has made significant progress in multiple myeloma for example. Recent attempt to use artificial intelligence may help simplify the algorithm for testing and may help avoid inter-observer variation and operator dependency in these highly technically demanding testing process.

Adjuvant therapy of pancreatic cancer.

Adjuvant therapy for pancreatic cancer remains controversial. However, both sides of the Atlantic Ocean agree that at least gemcitabine should be the pivotal agent offered to all patients. The role of radiation therapy remains somewhat inconclusive but chemoradiation, whether in the neoadjuvant or adjuvant setting is a standard option often utilized in the USA. This review is an update from the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL, USA. We present the summary of the findings from Abstracts #4020, #4021, #4040 and #4049 and discuss the impact on this group of patients. 

Multidisciplinary supportive care in systemic light chain amyloidosis.

The immunoglobulin light-chain amyloidosis is a multisystemic disease which manifests by damage to the vital organs by light chain-derived amyloid fibril. Traditionally, the treatment has been directed to the underlying plasma cell clone with or without high dose chemotherapy followed by autologous stem cell transplantation using melphalan based conditioning. Now with the approval of highly tolerable anti-CD38 monoclonal antibody daratumumab based anti-plasma cell therapy in 2021, high rates of hematologic complete responses are possible even in patients who are otherwise deemed not a candidate for autologous stem cell transplantation. However, despite the progress, there remains a limitation in the strategies to improve symptoms particularly in patients with advanced cardiac involvement, those with nephrotic syndrome and autonomic dysfunction due to underlying systemic AL amyloidosis. The symptoms can be an ordeal for the patients and their caregivers and effective strategies are urgently needed to address them. The supportive care is aimed to counteract the symptoms of the disease and the effects of the treatment on involved organs' function and preserve patients' quality of life. Here we discuss multidisciplinary approach in a system-based fashion to address the symptom management in this dreadful disease. In addition to achieving excellent anti-plasma cell disease control, using treatment directed to remove amyloid from the vital organs can theoretically hasten recovery of the involved organs thereby improving symptoms at a faster pace. Ongoing phase III clinical trials of CAEL-101 and Birtamimab will address this question.

Recent Advances in the Treatment and Supportive Care of POEMS Syndrome.

POEMS is a rare clonal plasma cell disorder characterized by multi-systemic features that include demyelinating peripheral neuropathy, organomegaly, endocrinopathy, presence of monoclonal proteins (M-protein), and skin changes. Even though the pathophysiology is poorly understood, recent studies suggest that both clonal and polyclonal plasmacytosis leading to the production of pro-inflammatory cytokines and angiogenic mediators play the central role. These mediators including vascular endothelial growth factor (VEGF) are the driving forces of the syndrome. The diagnosis of POEMS is not always straight forward and often the diagnosis is delayed. It is based on fulfilling mandatory criteria of polyradiculoneuropathy and monoclonal protein and the presence of one major criterion (Castleman disease, sclerotic bone lesions, or elevated VEGF), and at least one minor criterion. Due to the presence of neuropathy, it can be confused with chronic inflammatory demyelinating polyradiculopathy (CIDP), and if thrombocytosis and splenomegaly are present, it can be confused with myeloproliferative neoplasms. Due to the rarity of the syndrome, clear guidelines for treatment are still lacking. Immediate treatment targeting the underlying plasma cell proliferation results in a dramatic response in most patients. The key is early diagnosis and immediate anti-plasma cell directed therapy for the best clinical outcomes. For patients with disseminated disease as defined by bone marrow involvement or more than three osteosclerotic bone lesions, high-dose chemotherapy with autologous hematopoietic stem cell transplant (ASCT) yields durable responses and is the preferred treatment in eligible patients. For patients with localized bony disease, radiotherapy has proven to be very effective. Lenalidomide and dexamethasone is a proven therapy in patients ineligible for ASCT. In this review article, we tackle the diagnostic approach and discuss the latest treatment modalities of this rare debilitating disease.

Utility of Bruton's Tyrosine Kinase Inhibitors in Light Chain Amyloidosis Caused by Lymphoplasmacytic Lymphoma (Waldenström's Macroglobulinemia).

Of the variety of immunoglobulin related amyloidosis (AL), immunoglobulin M (IgM) related AL represents only 6 to 10% of affected patients, and the majority of these cases are associated with underlying non-Hodgkin's Lymphoma including Waldenström's macroglobulinemia (WM). Ibrutinib, acalabrutinib, and zanubrutinib are Bruton tyrosine kinase (BTK) inhibitors approved for certain indolent B cell non-Hodgkin's lymphoma (NHL). BTK is a nonreceptor kinase involved in B-cell survival, proliferation, and interaction with the microenvironment. We retrospectively evaluated the tolerability and effectiveness of BTK inhibitors ibrutinib and acalabrutinib therapy in (n = 4) patients with IgM-related AL amyloidosis with underlying WM. Treatment was well tolerated with both hematologic and organ response in patients with AL amyloidosis in the setting of WM. Atrial fibrillation led to the discontinuation of ibrutinib in one patient, and acalabrutinib caused significant thumb hematoma needing dose reduction in another patient. All patients evaluated had the MYD88 mutation. This may explain the good response to BTK inhibitors therapy in our series. BTK inhibitors should be further investigated in larger prospective studies for treatment of AL amyloidosis in patients with lymphoplasmacytic lymphoma/WM.

A Synopsis Clonal Hematopoiesis of Indeterminate Potential in Hematology.

Clonal hematopoiesis of indeterminate potential can be defined as genetic mutations that correlate in hematologic neoplasia such as myelodysplastic syndrome. Patients with cytopenia increasingly undergo molecular genetic tests of peripheral blood or bone marrow for diagnostic purposes. Recently, a new entity has been demarcated to lessen the risk of incorrect diagnoses of hematologic malignancies. This new entity is a potential precursor of myeloid diseases, analogous to monoclonal gammopathy of undetermined significance as a potential precursor of multiple myeloma.

Adhesion molecules in multiple myeloma oncogenesis and targeted therapy.

Every day we march closer to finding the cure for multiple myeloma. The myeloma cells inflict their damage through specialized cellular meshwork and cytokines system. Implicit in these interactions are cellular adhesion molecules and their regulators which include but are not limited to integrins and syndecan-1/CD138, immunoglobulin superfamily cell adhesion molecules, such as CD44, cadherins such as N-cadherin, and selectins, such as E-selectin. Several adhesion molecules are respectively involved in myelomagenesis such as in the transition from the precursor disorder monoclonal gammopathy of undetermined significance to indolent asymptomatic multiple myeloma (smoldering myeloma) then to active multiple myeloma or primary plasma cell leukemia, and in the pathological manifestations of multiple myeloma.

Challenges of Managing Multiple Myeloma Patients with Sickle Cell Disease: A Case Report and Review of Literature.

BACKGROUND A congenital hemolytic anemia, sickle cell disease can present with various clinical findings. Sickle cell disease is typically a disease of younger people and multiple myeloma typically occurs in older individuals. Multiple myeloma is rare among patients with sickle cell disease. Both multiple myeloma and sickle cell disease can cause various types of organ damage by different mechanisms. CASE REPORT We report a case of a patient who was born with sickle cell disease and presented with multiple myeloma later in life. Although he responded to anti-myeloma therapy, he died of hepatic and renal failure from complications of both multiple myeloma and sickle cell disease. CONCLUSIONS We discuss the complexity involved and present a review of the literature on managing multiple myeloma in relation to hepatic iron overload and end-stage renal disease in the setting of multiple myeloma and underlying sickle cell disease.

Management of Primary Plasma Cell Leukemia Remains Challenging Even in the Era of Novel Agents.

Primary plasma cell leukemia (PCL) is a rare and aggressive variant of multiple myeloma (MM). PCL is characterized by peripheral blood involvement by malignant plasma cells and an aggressive clinical course leading to poor survival. There is considerable overlap between MM and PCL with respect to clinical, immunophenotypic, and cytogenetic features, but circulating plasma cell count exceeding 20% of peripheral blood leukocytes or an absolute plasma cell count of >2000/mm3 distinguishes it from MM. After initial stabilization and diagnosis confirmation, treatment of PCL in a fit patient typically includes induction combination chemotherapy containing novel agents typically, with proteasome inhibitors (such as bortezomib) and immunomodulatory drugs (eg, lenalidomide), followed by autologous hematopoietic stem cell transplant (HSCT) and multidrug maintenance therapy using novel agents post-HSCT. Long-term outcomes have improved employing this strategy but the prognosis for non-HSCT candidates remains poor and new approaches are needed for such PCL patients not eligible for HSCT. Here, we report a case of primary PCL, and a comprehensive and up to date review of the literature for diagnosis and management of PCL. We also present the findings of Positron Emission Tomography (PET) scan. Since PCL is often associated with extra-medulary disease, including PET scan at the time of staging and restaging may be a novel approach particularly to evaluate the extra-medullary disease sites.

Liver failure due to relapsed myeloma and hepatic iron overload.

Multiple myeloma is a hematologic malignancy that classically manifests with hypercalcaemia, renal insufficiency, anaemia and lytic bone lesions. Liver dysfunction in multiple myeloma is a lesser known complication that occurs through biliary obstruction, liver infiltration by plasma cells, amyloid/light chain deposition or due to liver injury from medications. Although transfusion-related hepatic iron overload-leading to significant liver disease-is a recognised complication in certain hematologic malignancies, little is known about transfusional iron overload in patients with multiple myeloma. We present a case of a 49-year-old female with relapsed/refractory multiple myeloma who presented with rapid onset liver failure, due to both iron deposition and malignant plasma cell infiltration of the liver as a terminal event. A review of the literature on hepatic complications in multiple myeloma patients is presented.