scholarly journals Clinical considerations about the coexistence of melanoma and chronic lymphocytic leukemia in the era of targeted therapies, triggered by rare clinical scenarios. A case series and review of the literature

2020 ◽  
Vol 12 ◽  
pp. 175883592096236
Author(s):  
Panagiotis T. Diamantopoulos ◽  
Dimitrios Ziogas ◽  
Nora-Athina Viniou ◽  
Amalia Anastasopoulou ◽  
Georgios Kyriakakis ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Present Article ◽  
Targeted Therapies ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Lymphocytic Leukemia ◽  
Skin Cancer Screening ◽  
Clinical Scenarios ◽  
Anti Cd20 ◽  
The Impact

The epidemiologic correlation of melanoma and chronic lymphocytic leukemia (CLL) has been the subject of several population studies. In the present article, through the presentation of five illustrative cases of patients with melanoma and CLL, several aspects of this complex relationship are highlighted, with a focus on the increased incidence of melanoma in patients with CLL, its speculated etiology, and the impact of CLL stage and disease duration on the incidence and prognosis of melanoma. Furthermore, the rare entity of the synchronous diagnosis of melanoma and CLL in biopsied lymph nodes is discussed, along with its implications on the diagnostic and therapeutic procedures. In addition, the available data on the treatment choices in patients with melanoma and CLL are presented and the efficacy and safety of fludarabine, anti-CD20 monoclonal antibodies, new targeted therapies for CLL, and checkpoint inhibitors are further discussed. Finally, since no formal guidelines are available for the management of this group of patients, guidelines are proposed for skin-cancer screening in patients with CLL, for the correct interpretation of BRAF mutation analysis in lymph-node specimens with ‘collision of tumors,’ and for the optimal use of imaging studies in the diagnosis of metastatic disease in patients with CLL and melanoma, while a treatment approach for such patients is also suggested. The information and proposed guidelines provided in the present article comprise a useful guide for physicians managing such patients, focusing on diagnostic challenges and therapeutic dilemmas posed by the coexistence of the two disease entities.

scholarly journals The impact of immune checkpoint inhibitors in patients with chronic lymphocytic leukemia (CLL)

Medicine ◽  
2020 ◽  
Vol 99 (28) ◽  
pp. e21167
Author(s):  
Aviwe Ntsethe ◽  
Phiwayinkosi Vusi Dludla ◽  
Tawanda Maurice Nyambuya ◽  
Siphamandla Raphael Ngcobo ◽  
Bongani Brian Nkambule
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Lymphocytic Leukemia ◽  
The Impact

Impact of immunotherapy on survival differences in patients with melanoma and chronic lymphocytic leukemia.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21550-e21550
Author(s):  
Raghav Tripathi ◽  
Jeremy S. Bordeaux ◽  
Luke Rothermel ◽  
Ankit Mangla
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Lymphocytic Leukemia ◽  
Average Survival ◽  
Melanoma Patients ◽  
The Difference ◽  
Survival Differences ◽  
The Impact ◽  
Hispanic White

e21550 Background: Chronic lymphocytic leukemia (CLL) is well known to be associated with secondary malignancies like melanoma. Patients with melanoma and CLL are known to have poorer prognosis compared to patients without CLL. Checkpoint inhibitors (CPI) started gaining traction in 2011 after ipilimumab approval and are widely used in treatment of advanced melanoma. The objective of this study is to determine the survival of patients with melanoma and CLL in the era of CPI (2011 onwards) compared to previous years. Methods: We identified patients with melanoma and CLL reported to the Surveillance, Epidemiology, and End Results (SEER-18) program. We created cohorts of patients with melanoma and CLL vs. melanoma without CLL and split the cohorts into patients diagnosed from 2000-2010 and 2011-2017 to evaluate the impact of immunotherapy on overall all-cause survival. Kaplain-Meier survival curves were created for each of the four cohorts using the Ederer/direct-adjusted survival method. Standard Cox regression models adjusted for age and sex used to compare survival between subgroups. Two-sided p-values < 0.05 were considered significant. Results: From 2000-2017, 536,264 patients with melanoma were included in this study. 2,945 [0.55%] patients had coexisting CLL. Most patients were male (303,477 [56.6%]), age 60-79 (235,833 [44.0%]), non-Hispanic white (499,151 [93.08%]), and diagnosed from 2000-2010 (285,292 [53.2%]) with melanoma of the trunk (156,722 [29.2%]). From 2000-2010, patients with melanoma had an average survival of 91.4 months (95% CI 88.7-94.1) and those with coexisting CLL had an average survival of 59.3 months (95% CI 58.1-60.6). From 2011-2017, patients with melanoma had an average survival of 129.1 months (95% CI 127.7-130.5) and those with coexisting CLL had an average survival of 116.0 months (95% CI 113.5-118.5). The difference in survival in patients with melanoma vs. melanoma and CLL in 2000-2010 (32.1 months) is significantly greater than that of patients from 2011-2017 (13.1 months, p < 0.05). Conclusions: Although CLL continues to confer a survival disadvantage in patients with melanoma, the survival of patients with CLL and melanoma is better in the CPI-era. We also demonstrate that in the CPI era the gap between the survival of patients with melanoma and CLL and melanoma alone is also reducing significantly.

scholarly journals Sequencing of chronic lymphocytic leukemia therapies

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 128-136 ◽  
Author(s):  
Jacqueline C. Barrientos
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Selective Inhibition ◽  
Lymphocytic Leukemia ◽  
Sequencing Data ◽  
Combination Strategies ◽  
High Risk Disease ◽  
Approved Drugs ◽  
Anti Cd20 ◽  
The Impact

Abstract It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in frontline, relapsed, refractory, and high-risk disease. Traditionally, frontline management of CLL has been a combination of chemotherapy (fludarabine, cyclophosphamide, bendamustine, or chlorambucil) with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab). The current landscape is rapidly evolving with the advent of therapies that demonstrate selective inhibition of important pathways necessary for CLL proliferation and survival. Despite considerable progress, much is still unknown and optimal treatment selection and sequence is still debatable. None of the new agents have been compared against each other and the impact of adding an additional agent to monotherapy is not yet fully elucidated. In routine clinical practice, the choice of therapy is based on nonrandomized comparisons, presence of comorbidities, and toxicity considerations. These recently approved drugs (ibrutinib, idelalisib, and venetoclax) are reporting excellent outcomes, including patients with high-risk disease such as 17p deletion (17p−) or TP53 mutations (TP53mut). Ibrutinib and venetoclax have been approved for use in 17p− patients (frontline and relapsed, respectively). Ibrutinib is currently moving into the frontline space given recent regulatory approvals. This review will summarize and interpret the limited therapeutic sequencing data available, highlighting the need for additional studies to optimize combination strategies and treatments after failure or discontinuation of these novel agents.

scholarly journals Impact of DaTscan Imaging on Clinical Decision Making in Clinically Uncertain Parkinson’s Disease

2021 ◽  
pp. 1-5
Author(s):  
Jonathan R. Isaacson ◽  
Salima Brillman ◽  
Nisha Chhabria ◽  
Stuart H. Isaacson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Diagnosis ◽  
Clinical Decision Making ◽  
Photon Emission ◽  
Case Series ◽  
Emission Computed Tomography ◽  
Medication Therapy ◽  
Clinical Scenarios ◽  
The Impact

Background: The diagnosis of Parkinson’s disease (PD) is primarily clinical, but in cases of diagnostic uncertainty, evaluation of nigrostriatal dopaminergic degeneration (NSDD) by imaging of the dopamine transporter using DaTscan with single-photon emission computed tomography (SPECT) brain imaging may be helpful. Objective/Methods: In the current paper, we describe clinical scenarios for which DaTscan imaging was used in a prospective case series of 201 consecutive patients in whom a movement disorder specialist ordered DaTscan imaging to clarify NSDD. We describe the impact of DaTscan results on changing or confirming pre-DaTscan clinical diagnosis and on post-DaTscan treatment changes. Results/Conclusion: DaTscan imaging can be useful in several clinical scenarios to determine if NSDD is present. These include in patients with early subtle symptoms, suboptimal response to levodopa, prominent action tremor, drug-induced parkinsonism, and in patients with lower extremity or other less common parkinsonism clinical presentations. We also found DaTscan imaging to be useful to determine underlying NSDD in patients with PD diagnosis for 3-5 years but without apparent clinical progression or development of motor fluctuations. Overall, in 201 consecutive patients with clinically questionable NSDD, DaTscan was abnormal in 58.7% of patients, normal in 37.8%, and inconclusive in 3.5%. DaTscan imaging changed clinical diagnosis in 39.8% of patients and led to medication therapy changes in 70.1% of patients.

scholarly journals Challenges with Approved Targeted Therapies against Recurrent Mutations in CLL: A Place for New Actionable Targets

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3150
Author(s):  
Irene López-Oreja ◽  
Heribert Playa-Albinyana ◽  
Fabián Arenas ◽  
Mónica López-Guerra ◽  
Dolors Colomer
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Targeted Therapies ◽  
Biological Pathways ◽  
Lymphocytic Leukemia ◽  
Pi3k Inhibitors ◽  
Recurrent Mutations ◽  
Treatment Responses ◽  
Few Data ◽  
High Degree ◽  
Btk Inhibitors

Chronic lymphocytic leukemia (CLL) is characterized by a high degree of genetic variability and interpatient heterogeneity. In the last decade, novel alterations have been described. Some of them impact on the prognosis and evolution of patients. The approval of BTK inhibitors, PI3K inhibitors and Bcl-2 inhibitors has drastically changed the treatment of patients with CLL. The effect of these new targeted therapies has been widely analyzed in TP53-mutated cases, but few data exist about the response of patients carrying other recurrent mutations. In this review, we describe the biological pathways recurrently altered in CLL that might have an impact on the response to these new therapies together with the possibility to use new actionable targets to optimize treatment responses.

scholarly journals The Impact of Chlorambucil and Valproic Acid on Cell Viability, Apoptosis and Expression of p21, HDM2, BCL2 and MCL1 Genes in Chronic Lymphocytic Leukemia

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1088
Author(s):  
Katarzyna Lipska ◽  
Agata Filip ◽  
Anna Gumieniczek
Keyword(s):  
Valproic Acid ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Viability ◽  
Antiepileptic Drug ◽  
Drug Combination ◽  
Target Genes ◽  
Histone Deacetylation ◽  
Lymphocytic Leukemia ◽  
Malignant Cells ◽  
The Impact

Malignant cells in chronic lymphocytic leukemia (CLL) show resistance to apoptosis, as well as to chemotherapy, which are related to deletions or mutations of TP53, high expression of MCL1 and BCL2 genes and other abnormalities. Thus, the main goal of the present study was to assess the impact of chlorambucil (CLB) combined with valproic acid (VPA), a known antiepileptic drug and histone deacetylation inhibitor, on apoptosis of the cells isolated from 17 patients with CLL. After incubation with CLB (17.5 µM) and VPA (0.5 mM), percentage of apoptosis, as well as expression of two TP53 target genes (p21 and HDM2) and two genes from Bcl-2 family (BCL2 and MCL1), were tested. As a result, an increased percentage of apoptosis was observed for CLL cells treated with CLB and VPA, and with CLB alone. Under the treatment with the drug combination, the expression of p21 gene was visibly higher than under the treatment with CLB alone. At the same time, the cultures under CLB treatment showed visibly higher expression of BCL2 than the cultures with VPA alone. Thus, the present study strongly suggests further investigations on the CLB and VPA combination in CLL treatment.

Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series

2017 ◽  
Vol 76 (12) ◽  
pp. 2061-2064 ◽  
Author(s):  
Sang Taek Kim ◽  
Jean Tayar ◽  
Van Anh Trinh ◽  
Maria Suarez-Almazor ◽  
Salvador Garcia ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Unmet Need ◽  
Case Series ◽  
Receptor Antibody ◽  
Improved Outcomes ◽  
Clinical Scenarios ◽  
Significant Clinical Improvement ◽  
Tnfα Inhibitor ◽  
Factor Α

BackgroundImmune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with numerous cancers. However, these therapies are associated with immune-related adverse events (irAEs), which are inflammatory side effects potentially affecting any organ. Cases of ICI-induced inflammatory arthritis have also been reported. In general, mild irAEs are treated with corticosteroids, while tumour necrosis factor-α (TNFα) inhibitors are reserved for refractory cases. However, prolonged use of TNFα inhibitor (TNFαi) can induce widespread, significant immunosuppression, which can negatively impact the antitumour efficacy of ICI therapy. Therefore, in clinical scenarios where patients develop severe immunotherapy-induced irAEs, an unmet need exists for alternative therapeutic strategies that are effective and without immune dampening effects.Case reportsThe anti-interleukin (IL)−6 receptor antibody, tocilizumab, is a biological agent Food and Drug Administration approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Here, we report on three patients who developed severe polyarthritis while receiving ICI therapy and were treated with tocilizumab. All three patients demonstrated significant clinical improvement; one patient maintained a durable antitumour response derived from checkpoint inhibition.ConclusionsThese three cases suggest that anti-IL-6 receptor antibody may be an effective alternative to corticosteroids or TNFαi for the treatment of arthritis irAEs.

scholarly journals Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Deborah M. Stephens ◽  
Ken Boucher ◽  
Elizabeth Kander ◽  
Sameer A. Parikh ◽  
Erin M. Parry ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hodgkin Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Small Sample Size ◽  
Case Series ◽  
Standard Of Care ◽  
Median Number ◽  
Small Sample ◽  
Lymphocytic Leukemia ◽  
Treatment Type

Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of patients with Hodgkin Transformation (HT) of CLL. Clinicobiologic characteristics, treatment type, and survival outcomes were analyzed and compared with historic case series. Ninety-four patients were identified. Median age at HT was 67 years (range, 38-85). Median time from CLL diagnosis to HT was 5.5 years (range, 0-20.2). Prior to HT, patients received a median of 2 therapies for CLL (range, 0-12). As initial therapy for HT, 61% (n=62) received ABVD-based regimens (adriamycin, bleomycin, vinblastine, and dacarbazine). Seven (7%) patients received hematopoietic cell transplantation (HCT) while in first complete remission (CR1). The median number of treatments for HT per patient was 1 (range, 0-5) with 59 (61%) patients only receiving one line of therapy. After HT, patients had a median follow-up of 1.6 years (range, 0-15.1). Two-year overall survival (OS) after HT diagnosis was 72% (95%CI 62-83%). The patients who received standard ABVD-based therapy had a median OS of 13.2 years. Although limited by small sample size, the patients who underwent HCT for HT in CR1 had a similar 2-year OS (n=7; 67%) compared to patients who did not undergo HCT for HT in CR1 (n=87; 72%; p=0.46). In this multi-center study, HT patients treated with ABVD-based regimens had prolonged survival supporting the use of these regimens as standard of care for these patients.

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