- |||||||||| Brukinsa (zanubrutinib) / BeiGene, Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Global Waldenström’s Macroglobulinemia Patient-Derived Data Registry, Whimsical, Highlights Real-World Treatment Outcomes and COVID-19 Data (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2911;
The data highlight the real-world efficacy of combination chemoimmunotherapy, particularly first-line BR, and suggest a better QoL with BTKi than other therapies. As this global data platform grows, the breadth of data allows for new insights into WM with patient reported outcomes advancing knowledge and facilitating treatment decisions for clinicians and patients.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen
First Prospective Data on Minimal Residual Disease (MRD) Outcomes after Fixed-Duration Ibrutinib Plus Venetoclax (Ibr+Ven) Versus Chlorambucil Plus Obinutuzumab (Clb+O) for First-Line Treatment of CLL in Elderly or Unfit Patients: The Glow Study (GWCC - Thomas Murphy Ballroom 3-4, Level 5) - Nov 5, 2021 - Abstract #ASH2021ASH_1283;
P3
Most pts with uMRD in the Ibr+Ven arm, including those with uIGHV, achieved clearance below 10 -5 , and deeper clearance in PB was mirrored in BM. In the Ibr+Ven arm, clinical relapse was infrequent during the first year off treatment for pts with known MRD status at EOT+3 (whether uMRD or detectable MRD), supported by largely sustained uMRD/MRD levels over the same period.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Chronic Lymphocytic Leukemia in a Cockatiel (Nymphicus hollandicus). (Pubmed Central) - Nov 1, 2021
The bird was euthanatized 15 months after the initial diagnosis and 8 months after treatment commenced. On the postmortem examination, extensive T-cell lymphocytic infiltration was found throughout the internal organs.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Journal: Pathophysiology, diagnosis, and treatment of membranous nephropathy. (Pubmed Central) - Oct 30, 2021
Antibody removal using immunoadsorption or plasmapheresis leads to short-term reduction in proteinuria and might be indicated only in patients with very severe proteinuria and complications. Studies are needed to identify a more specific immunosuppression directed against the production and effects of autoantibodies in order to protect the kidneys from autoimmune mediated tissue damage and to identify patients who require an immunosuppressive treatment, as the remission rate is high in patients with MN.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] RICHTER SYNDROME: CASE REPORT OF LLC TO LCMB TRANSFORMATION () - Oct 27, 2021 - Abstract #HEMO2021HEMO_1455;
Studies are needed to identify a more specific immunosuppression directed against the production and effects of autoantibodies in order to protect the kidneys from autoimmune mediated tissue damage and to identify patients who require an immunosuppressive treatment, as the remission rate is high in patients with MN. Richter's Syndrome (RS) is a rare condition characterized by the transformation of chronic lymphocytic leukemia (CLL) most frequently into diffuse large B-cell lymphoma (LDCBG); however, less commonly, it can develop into blastoid mantle cell lymphoma (LCMB). The etiology of RS is unknown so far; no genetic predispositions or a single alteration responsible for this transformation from LLC to LCMB have yet been identified. Its incidence is rare, with CLL transformation occurring in 2% to 6% of cases, and of these, it is believed to occur in < 3% of cases due to lack of evidence in the literature. Diagnosis is made by bone marrow biopsy, altered lymph node biopsy, and immunohistochemical markers. Treatment is based on chemotherapy and may include stem cell transplantation. This study aims to report and discuss the transformation of LCC into LCMB. Since, despite its rare incidence, it has an aggressive and high-grade course, early diagnosis is necessary for a better prognosis for the patient. We report the case of a 63-year-old male patient, former heavy smoker, former heavy drinker, diagnosed with CLL in 2011 under treatment. Chemotherapy started with 1 cycle of rituximab in 2017, not responding to therapy. Rescue therapy was attempted in 2018 with rituximab + dexamethasone + cyclophosphamide, without success. Started in 2019 chlorambucil, with response for 7 cycles. Upon admission in 2020, for follow-up with the hematology service in a general hospital for further CLL treatment, the patient is refractory. At ectoscopy, a bulky mass in the left cervical region. Laboratory tests showed macrocytic anemia, leukopenia and thrombocytopenia. Bone marrow imaging and biopsy revealed splenomegaly, paraesophageal, retrocural, mesenteric lymph node enlargement and the following biochemical markers: CD20+; PAX-5+; CD5+; cyclin+; BCL2+; Ki67+; CD43+; CD3+; SOX-11+; MUM-1+; CD23-; CD10-; BCL6-; All-. We conclude the diagnosis of Richter's syndrome with transformation from LLC to LCMB, a rare condition potentially related to immunosuppression caused by chronic lymphoproliferative disease of unknown etiology. The patient's evolution to the new therapy, the R-CHOP chemotherapy protocol, showed an improvement in the clinical picture in the first cycle. In the meantime until the second cycle, the patient contracts SARS-CoV-2 and progresses to death due to the infection.
- |||||||||| Leukeran (chlorambucil) / GSK
[VIRTUAL] CONCOMITANCES OF TWO CHRONIC NON-PHILADELPHIA MYELOPROLIFERATIVE SYNDROMES: A CASE REPORT () - Oct 27, 2021 - Abstract #HEMO2021HEMO_497;
Introduction Polycythemia vera (PV), the world's most prevalent myeloproliferative neoplasm, is characterized by increased red blood cell mass, usually associated with the presence of a mutation in the JAK2 gene (V617F mutation). This increase promotes blood hyperviscosity which determines the clinical and complications as a thrombotic event. Chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and accumulation of mature B cells in the blood, bone marrow, lymph nodes, and spleen. It is more prevalent in men, its mean age is 72 years at diagnosis and its incidence increases with age. Case report ER, 84, male, brought recent consecutive laboratory tests that showed a number of red blood cells > 6 million/mm3, hemoglobin > 17.4 g/dL, hematocrit > 52% and leukometry greater than 15,900/mm3 (at the expense of segmented neutrophils and lymphocytes) without associated infection. He had a history of deep venous thrombosis in his left lower limb, requiring the use of Xarelto for 6 months. The patient was then asked for some tests to suspect the diagnosis of PV, which was confirmed by the presence of the mutation in the JAK-2 gene and was classified as high risk. Two 500 mg hydroxyurea tablets per day, biweekly bloodletting of 450 mL for 1 month with subsequent blood count as initial conduct were prescribed. During follow-up, there was an improvement in the blood count, with no need for further bloodletting and oral hydroxyurea was maintained with biweekly control. Subsequently, the dose of the drug was reduced to 1 tablet/day interspersed with 2 tablets/day, with subsequent stabilization of the condition. During follow-up, the patient had anemia with atypical lymphocytosis, so immunophenotyping was requested, which identified a percentage of 66.5% of B lymphocytes, CD23+, CD5+, CD43+, CD200 strong and CD79b negative, concluding a diagnosis of CLL concomitant with the diagnosis previous of PV. Afterwards, the dose of hydroxyurea was reduced to 1 tablet/day, aiming to improve the erythrogram, and more frequent monitoring was installed to check the PV, which soon stabilized. Between 2017 and 2018, it expressed progressive lymphocytosis up to 48,560/mm3 without associated symptoms, so frequent clinical monitoring with laboratory tests and symptom verification was instituted. In the following follow-ups, he had a WBC of 79,650/mm3, and a new therapy with 7-day courses of oral Leukeran with 6 tablets/day was implemented to treat CLL, which were well tolerated. Finally, the patient is in remission of the leukemic condition and with resolution of PV.Discussion The V617F mutation in the JAK2 gene is frequent in non-Philadelphia Chronic Myeloproliferative Syndromes, the time at which it occurs is still unknown, but recent studies show that it occurs in both bloodlines. In these patients who have hydroxurea as one of their therapeutic medications, a more rigorous follow-up with frequent blood counts is necessary due to the risk of the patient developing a future leukemia.Conclusion Both PV and CLL are important hematopoietic pathologies that are related to each other by its origin in the same genetic mutation. Therefore, it is possible that the patient developed CLL after PV due to the genetic mutation itself or, more likely, due to the use of hydroxyurea.
- |||||||||| Leukeran (chlorambucil) / GSK
[VIRTUAL] CLINICAL, LABORATORY CHARACTERISTICS AND TREATMENTS PERFORMED IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA IN THE SOROCABA HOSPITAL UNIT () - Oct 27, 2021 - Abstract #HEMO2021HEMO_462;
Objective To draw an epidemiological and clinical profile of patients with Chronic Lymphocytic Leukemia (CLL) treated at the Sorocaba Hospital Complex (CHS).Material and Methods Evaluation of medical records of patients diagnosed with CLL in the last 3 years, aiming to compute demographic and clinical characteristics , laboratory, staging, therapy and current situation. The compiled data will be entered into the Brazilian Registry of Chronic Lymphocytic Leukemia.Result Thirty-five patients were evaluated, of which 9 were women (37%) and 15 men (63%). The mean age of patients at diagnosis was 68 years, with 25 white patients (71.5%), 1 black (3%) and 9 with no information in the medical record (25.5%); as to the origin, 17 patients living in neighboring cities (77%) and 7 in the city of Sorocaba (23%). As for symptoms and signs at diagnosis, 2 patients had fever (6%), 1 night sweats (3%), 8 weight loss (24%), 18 lymph node enlargement (52%), 9 fatigue (26%), 11 splenomegaly (31 %), in addition to 13 asymptomatic (37%) and 8 without available information (24%). Regarding laboratory data, 33 patients had lymphocytosis (95%), 11 anemia (31.5%), 5 neutropenia (14%), 10 thrombocytopenia (28%). Immunophenotyping indicated CD-5 positivity in 32 patients (91.5%), CD-19 in 23 (65%), CD-20 in 22 (63%) and CD-23 in 27 (77%). Twenty patients in stage A (57%), 8 in stage B (23%) and 7 in stage C (20%) of Binet were observed. As for treatment, 15 patients used Chlorambucil (43%), 7 FC (20%), 4 COP (11.5%), 2 mini CHOP (6%), 2 FC light (6%) , 1 of Fludarabine + Prednisone (3%), 1 of Pulse Therapy (3%), 1 of Cyclophosphamide (3%), 1 of Chlorambucil + Prednisone (3%) and 13 did not undergo treatment (37%). Discussion and Conclusion s O predominance of men and the average age at diagnosis follow what is described in the literature. The mostly white ethnicity is consistent with most studies. The main symptoms mentioned in the literature, such as fatigue, weakness, weight loss, lymphadenopathy and splenomegaly were observed, but asymptomatic patients were not as prevalent as expected. Lymphocytosis was present in 95% of patients, following the pattern expected in the literature. However, there was no significant prevalence of cytopenias. Immunophenotyping with expression of CD-5, CD-19, CD-20 and CD-23 were characteristic. As for the Binet staging, most patients were diagnosed at stage A (57%). Because of this, a more expectant approach would be expected, however, 63% of patients underwent treatment. This was due to the lower proportion of asymptomatic patients compared to the literature, which defined the indication for treatment. As for medications, there is a predominance of the use of Chlorambucil, due to the characteristics of the patients and because it is a service that serves the SUS.
- |||||||||| Leukeran (chlorambucil) / GSK
[VIRTUAL] ASCITE AS A MANIFESTATION OF CHRONIC LYMPHOCYTIC LEUKEMIA () - Oct 27, 2021 - Abstract #HEMO2021HEMO_125;
Its initial stage was RAI/BINET: IIC with severe anemia that triggered the initiation of treatment with Chlorambucil. With the introduction of the treatment, there was an improvement in the ascites, but the patient maintained severe anemia and the chemotherapy regimen was switched to CVP (cyclophosphamide, vincristine and prednisone).
- |||||||||| Leukeran (chlorambucil) / GSK
Preclinical, Journal: 5-Arylidene-2-(4-hydroxyphenyl)aminothiazol-4(5H)-ones with selective inhibitory activity against some leukemia cell lines. (Pubmed Central) - Oct 22, 2021
The structure-activity relationship analysis shows that almost all tested 5-arylidene-2-(4-hydroxyphenyl)aminothiazol-4(5H)-ones were characterized by ІС values lower or comparable to that of the control drug chlorambucil. Among the tested compounds, (5Z)-5-(2-methoxybenzylidene)- (12), (5Z)-(2-ethoxybenzylidene)- (21), (5Z)-5-(2-benzyloxybenzylidene)- (25), and (5Z)-5-(2-allyloxybenzylidene)-2-(4-hydroxyphenylamino)thiazol-4(5H)-ones (28) possessed the highest antileukemic activity at submicromolar concentrations (ІС = 0.10-0.95 µM).
- |||||||||| Mustargen (mechlorethamine) / Recordati
Journal: Derivatives of nitrogen mustard anticancer agents with improved cytotoxicity. (Pubmed Central) - Oct 22, 2021
Melphalan was almost as effective as the target compounds-derivatization only provided a small improvement. The novel cytostatics are of interest as model compounds for analyzing a correlation between cytotoxicity and membrane transport and for the treatment of malignancies.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen
Clinical, P3 data, Journal, HEOR: Health-related quality of life with fixed-duration venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: Results from the randomized, phase 3 CLL14 trial. (Pubmed Central) - Oct 1, 2021
According to MDASI scores, CLL symptoms (1.5 [±1.2] and 1.6 [±1.3]), core cancer symptoms (1.5 [±1.4] and 1.8 [±1.7]) and symptom interference (2.1 [±2.3] and 2.3 [±2.3]) were generally low and comparable between treatment arms at baseline and were maintained throughout treatment and follow-up. This analysis demonstrates that the higher efficacy of Ven-Obi is not associated with QoL impairment and that Ven-Obi achieves early relief of CLL-related symptoms in elderly unfit patients.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Discovery of Potential Mitochondrial Transcription Inhibitors as Anticancer Agents by Transcriptomic Profiling. (Pubmed Central) - Sep 16, 2021
Previously, we repurposed chlorambucil by conjugating it to a mitochondrial targeting triphenylphosphonium (TPP) group to design Mito-Chlor, a novel agent that acts on mitochondria DNA (mtDNA)...Both compounds increased cellular and mitochondrial reactive oxygen species and stimulated similar signaling pathway. As mitochondrial transcription inhibitors and redox modulators, SQD1 and Mito-Chlor are promising for cancer treatment by manipulating mitochondrial function.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen
Journal: An update of venetoclax and obinutuzumab in chronic lymphocytic leukemia. (Pubmed Central) - Sep 8, 2021
Venetoclax, an oral anti-apoptotic BCL-2 inhibitor, in combination with a CD20 antibody has shown superiority to chemoimmunotherapy in treatment-naive and relapsed/refractory CLL. Obinutuzumab is a novel anti-CD20 monoclonal antibody that has been safely combined with novel agents including venetoclax and Bruton tyrosine kinase inhibitors and has shown superiority over rituximab when combined with chlorambucil.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Calquence (acalabrutinib) / AstraZeneca
[VIRTUAL] Acalabrutinib ± Obinutuzumab vs Obinutuzumab + Chlorambucil in Treatment-Naïve Chronic Lymphocytic Leukemia: ELEVATE-TN 4-Year Followup () - Sep 6, 2021 - Abstract #SOHO2021SOHO_513;
P3
Obinutuzumab is a novel anti-CD20 monoclonal antibody that has been safely combined with novel agents including venetoclax and Bruton tyrosine kinase inhibitors and has shown superiority over rituximab when combined with chlorambucil. With a median follow-up of 46.9 months (~4y), the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.
- |||||||||| Leukeran (chlorambucil) / GSK
[VIRTUAL] Diagnosis and Treatment Options in Low-Risk Chronic Lymphocytic Leukemia () - Sep 6, 2021 - Abstract #SOHO2021SOHO_507;
Interventions: Single-agent chemotherapy with chlorambucil was performed in older patients, with concomitant pathology... CLL was diagnosed commonly in males, aged 60-79 years and in stage A. The survival rates depended on a clinical stage and accounted 98.0% at one year and 77.3% at 5 years.
- |||||||||| [VIRTUAL] Case Presentation – Frontline Treatment of Older Patient with CLL: Options and Consideration () - Sep 6, 2021 - Abstract #SOHO2021SOHO_362;
Similarly, the ELEVATE-TN study with acalabrutinib ± obinutuzumab in the treatment-naïve older patient population demonstrated continued PFS benefit with the BTKiarms compared to chlorambucil-obinutuzumab leading to its approval in this setting.8 Currently BTKitherapy (± monoclonal antibody) requires indefinite inhibition and continuous therapy...Similarly, the ALPINE study noted reduced rates of atrial fibrillation/fl utter but also a superior objective response rate at an interim analysis in their study of zanubrutinib versus ibrutinib in relapsed/refractory CLL patients.10 Further long-term follow-up will be necessary to confirm if these early differences hold up with time...In addition, there was a higher complete response frequency and higher percentage of patients that were negative for minimal residual disease in both the peripheral blood and bone marrow for the venetoclax–obinutuzumab group than in the chlorambucil–obinutuzumab group...Similarly, the converse is true about a patient with poor renal function and/or inability for close follow-up and management of tumor lysis syndrome due to inadequate social support, and thus therapy with a BTKiwould be chosen. Older patients without any significant comorbidities to preclude any treatment options certainly have more fl exibility based on their desire for continuous versus a time-limited therapy and can take into consideration the timing and duration of therapy as well as the potential toxicities of these therapies.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
Review, Journal: Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. (Pubmed Central) - Aug 28, 2021
Notable adverse events such as grade 3 or 4 neutropenia can be managed with supportive therapy and venetoclax dose modifications. In conclusion, fixed-duration venetoclax + obinutuzumab represents an important chemotherapy-free first-line treatment option for patients with CLL, particularly those who are not fit enough to receive intensive chemoimmunotherapy.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, Reimbursement, Journal, Adverse events, HEOR, Medicare, Real-world evidence: Overall survival, adverse events, and economic burden in patients with chronic lymphocytic leukemia receiving systemic therapy: Real-world evidence from the medicare population. (Pubmed Central) - Aug 1, 2021
Our findings highlight considerable susceptibility to AEs and unmet medical need in Medicare patients with CLL treated in routine practice. Medicare incurred substantial economic burden following initiation of systemic therapy, and patients with greater numbers of AEs accounted disproportionately for the high overall cost of CLL management.
- |||||||||| Leukeran (chlorambucil) / GSK
Clinical, Journal, Real-world evidence: Chronic Lymphocytic Leukemia: Real-World Data From India. (Pubmed Central) - Jul 30, 2021
Treatment outcomes with biosimilar fixed-dose BR are comparable to those reported in the literature. Chlorambucil is still a valid option, given the economic burden of the disease and treatment.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, Journal: Epidemiology, Treatment Patterns, and Survival of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) in Taiwan, 2006-2015. (Pubmed Central) - Jul 28, 2021
The present case report suggests that FMT, possibly together with chlorambucil, might be a treatment option for NRE in Shiba dogs that have poorer prognosis compared with other dog breeds. This study is the first population-based study in Asia and provides comprehensive evidence of epidemiology, treatment patterns and survivals of CLL/SLL in an Asian population.
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