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Immunotherapy in hematologic malignancies: past, present, and future.

The field of immunotherapy in cancer treatments has been accelerating over recent years and has entered the forefront as a leading area of ongoing research and promising therapies that have changed the treatment landscape for a variety of solid malignancies. Prior to its designation as the Science Breakthrough of the Year in 2013, cancer immunotherapy was active in the treatment of hematologic malignancies. This review provides a broad overview of the past, present, and potential future of immunotherapy in hematologic malignancies.

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… This agent was FDA approved for the treatment of previously treated chronic lymphocytic leukemia (CLL) in 2009 or in combination with chlorambucil for the treatment of previously untreated CLL in 2014 [ 18 , 19 ]. … Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015;385:1873–1883. doi: 10.1016/S0140-6736(15)60027-7. 20. …

The Five "Ws" of Frailty Assessment and Chronic Lymphocytic Leukemia: Who, What, Where, Why, and When.

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, but chronological age does not accurately discriminate frailty status at the inter-individual level. Frailty describes a person's overall resilience. Since CLL is a stressful situation, it is relevant to assess the patient´s degree of frailty, especially before starting antineoplastic treatment. We are in the era of targeted therapies, which have helped to control the disease more effectively and avoid the toxicity of chemo (immuno) therapy. However, these drugs are not free of side effects and other aspects arise that should not

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… Most patients received chlorambucil (Chl)-based treatments (56.8%), with only six (10.3%) being treated with ibrutinib. Using these variables, they developed a frailty score that categorized patients into three groups: frail, pre-frail, and fit. … Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions N. Engl. J. Med. 2014 370 1101 1110 10.1056/NEJMoa1313984 24401022 97. Barr P.M. Owen C. Robak T. Tedeschi A. Bairey O. Burger J.A. Hillmen P. Coutre S.E. Dearden C. Grosicki S. …

Hematopoietic Tumors

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… . * Other drugs that also have activity and could be considered second-line agents include vinblastine, actinomycin-D, mitoxantrone, chlorambucil, methotrexate, DTIC, 9-aminocamptothecin, ifosfamide, cytosine arabinoside, gemcitabine, lomustine, and dolastatin-10. 206 , 207 , 208 , 209 , 210 , 211 , … If the patient develops sterile hemorrhagic cystitis while taking cyclophosphamide, the drug should be discontinued and chlorambucil (1.4 mg/kg, PO) should be given for subsequent scheduled cyclophosphamide injections. 4. …

Early-stage IgM kappa proliferative glomerulonephritis with monoclonal immunoglobulin deposition presenting with atypical renal insufficiency: a case report and literature review.

INTRODUCTION: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare subtype of monoclonal gammopathy of renal significance (MGRS). While the IgG subtype has been well characterized, the IgM-κ variant is extremely rare, with a low detection rate of circulating monoclonal proteins and limited real-world data on its clinical course under conservative management. This case report describes a biopsy-proven IgM-κ PGNMID in an elderly patient with negative hematological screening, to expand the current understanding of this rare entity. PATIENT CONCERNS AND DIAG

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… Reference | Age/Sex | Pathologic pattern | Glomerular deposits (IF) | C3 | Treatment | Renal outcome/follow-up Lima et al. ( 9 ) | 76/M | Mesangial proliferative, 40% crescents | Serum IgMκ (kidney IF not stained for κ) | Negative | Methylprednisolone+chlorambucil | Stable sCr 2 mg/dL, UP <1 g/24 h; … κ (2+), λ (−) | C3 (1–2+) | B + D (BRD stopped due to AE) | Resolved hematuria/proteinuria, stable sCr; >3 years Oe et al. ( 18 ) | 48/M | MPGN | IgM (3+), κ (2+), λ (−) | C3 (2+) | R-FC × 4period | Proteinuria ↓, sCr 1.5 mg/dL Ramos et al. ( 11 ) | 48/M | MPGN, 40% crescents | IgMκ | C3 (+) | Pred+Chlorambucil …

Waldenström macroglobulinemia treatment algorithm 2018.

Waldenström macroglobulinemia is often an indolent disorder, and many patients are candidates for observation with careful monitoring. For symptomatic patients, one must distinguish between those patients whose symptoms are related to immunologic manifestations associated with the IgM monoclonal protein and those that have symptoms related to progressive marrow and nodal infiltration with lymphoplasmacytic lymphoma. In Waldenström macroglobulinemia, the driver for therapy in the majority of patients is progressive anemia, secondary to bone marrow replacement by lymphoplasmacytic lymphoma. Rece

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… The trial compared chlorambucil, which is now used infrequently, versus oral fludarabine 41 . In this trial, fludarabine was superior to chlorambucil in terms of progression-free and overall survival. … Leblond V Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated Waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma J. Clin. Oncol. 2013 31 301 307 23233721 10.1200/JCO.2012.44.7920 42. …

DNA Damaging Drugs

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… Therefore, chlorambucil can be given orally in tablet form. Chlorambucil is indicated in the palliative treatment of chronic lymphocytic leukemia, malignant lymphoma, lymphosarcoma, giant follicular lymphoma, and Hodgkin disease. … Chlorambucil should not be used in patients whose disease has shown a prior resistance or known hypersensitivity to the agent. There may be cross-hypersensitivity between chlorambucil and other alkylating agents. …

Hematopoietic Tumors

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… Other drugs that have documented activity are often considered second-line agents and include rabacfosadine (Tanovea-CA1), lomustine, vinblastine, actinomycin-D, mitoxantrone, mustargen, chlorambucil, methotrexate, dacarbazine (DTIC), 9-aminocamptothecin, ifosfamide, cytosine arabinoside, procarbazine … If sterile hemorrhagic cystitis occurs on cyclophosphamide, discontinue and substitute chlorambucil (1.4 mg/kg PO) for subsequently scheduled cyclophosphamide treatments. 4. …

Antibodies to watch in 2013: Mid-year update.

The transitions of antibody therapeutics to late-stage clinical development, regulatory review and the market are proceeding at a rapid pace in 2013. Since late 2012, two monoclonal antibody (mAb) therapeutics (itolizumab, trastuzumab emtansine) received their first approvals, first marketing applications for three mAbs (vedolizumab, ramucirumab, obinutuzumab) were submitted to regulatory agencies, and five mAbs (brodalumab, MABp1, moxetumomab pasudotox, tildrakizumab, rilotumumab) entered their first Phase 3 studies. The current total of commercially-sponsored antibody therapeutics undergoing

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… The marketing applications were based on data from the 3-arm, Phase 3 CLL11 study ( NCT01010061 ), which compared the combination of either obinutuzumab or rituximab and chlorambucil to chlorambucil alone in patients with previously untreated chronic lymphocytic leukemia. …

Hematopoietic Tumors

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

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… Other drugs that have documented activity are often considered second-line agents and include lomustine, vinblastine, actinomycin-D, mitoxantrone, mustargen, chlorambucil, methotrexate, dacarbazine (DTIC), 9-aminocamptothecin, ifosfamide, cytosine arabinoside, and gemcitabine. …

Cost-effectiveness evidence on approved cancer drugs in Ireland: the limits of data availability and implications for public accountability.

BackgroundWe surveyed evidence published by Ireland's National Centre for Pharmacoeconomics (NCPE) on the cost-effectiveness of cancer drugs approved for funding within the Irish public healthcare system. The purpose is threefold: to assess the completeness and clarity of publicly available cost-effectiveness data of such therapies; to provide summary estimates of that data; to consider the implications of constraints on data availability for accountability regarding healthcare resource allocation.MethodsThe National Cancer Control Programme lists 91 drug-indication pairs approved between June

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… for adults with previously untreated chronic lymphocytic leukaemia (CLL) and with comorbidities making them unsuitable for full-dose fludarabine based therapy Leukemia-bmt/286 obinutuzumab-and-chlorambucil-therapy.pdf Drugs/obinutuzumab-gazyvaro/ Aug 2015 27 Pixantrone Monotherapy for adults with multiply … failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated After HTA PCRS 27 5 Yes 25 Radium 223 Adults with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastases After HTA ODMS 16 7 Yes 26 Obinutuzumab Combination with chlorambucil …

Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children.

BACKGROUND: About 80% of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. Of these children, half will relapse frequ … 95 children: RR 0.51, 95% CI 0.35 to 0.74) (low certainty). Alkylating agents (cyclophosphamide and chlorambucil) compared with prednisone probably reduce the number of children who experience relapse at six to 12 months (6 studies, 202 children: RR 0.44, 95% CI 0.32 to 0.60) and at 12 to 24 months (4 studies, 59 children: RR 0.20, 95% CI 0.09 to 0.46) (modera …

Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome.

BACKGROUND: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Without treatment, approximately 30% of … nform their patients of the lack of high-quality evidence. An alkylating agent (cyclophosphamide or chlorambucil) combined with a corticosteroid regimen had short- and long-term benefits, but this was associated with a higher rate of adverse events. CNI (tacrolimus and cyclosporin) showed equivalency with alkylating agents however, the certainty of this eviden …

Surrogate endpoints in mature B-cell neoplasms - meaningful or misleading?

Indolent mature B-cell neoplasms are a group of diseases in which recent therapeutic advances have led to an improved overall survival (OS) extending beyond several years. While cause of celebration for patients and caregivers, the increasingly long observation periods necessary to capture treatment effects are complicating trial design and possibly hindering swift access to more effective therapies. Surrogate endpoints are a tool with the potential of earlier study readouts, however, their validity needs to be proven in each individual disease and therapeutic setting. The validation of surrog

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… For example, CLL14 has shown clear superiority of venetoclax + obinutuzumab vs. chlorambucil + obinutuzumab in terms of PFS but OS differences have so far not crossed significance boundaries even after 6 years of follow-up [ 30 ]. … Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020;21:1188–200. 9. …

Progressive Multifocal Leukoencephalopathy after Administration of Front-Line Obinutuzumab and Venetoclax in a Patient with Chronic Lymphocytic Leukemia: Case Report.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal demyelinating disease of the central nervous system caused by the reactivation of the John Cunningham virus (JCV) in immunocompromised patients. Obinutuzumab is type II anti-CD 20 antibody, used in combination with venetoclax for chronic lymphocytic leukemia (CLL). CASE PRESENTATION: A 75-year-old female patient was diagnosed with PML after a short course of obinutuzumab and venetoclax started for a newly diagnosed CLL. There was no history of hepatitis B, C, or human-immunodeficiency virus. Quantitative

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… Paper (year) | Regimen | Symptoms | Laboratory findings | Neuroimaging | Treatment | Outcome Pejsa et al. [ 6 ] (2019) | Obinutuzumab + chlorambucil for CLL; 6 cycles completed | Blurred vision; later cognitive and neurological decline | CSF JC virus PCR positive | T2 hyperintense subcortical lesions … | CSF PCR: JCV 1.3 × 10 7 copies/mL; normal lymphocytes, no B cells | Extensive bilateral leukopathy (parietal, temporal, occipital, cerebellum) | Not reported | Not reported The next case was reported by Pejsa et al. [ 6 ] of a patient with CLL who developed PML after 6 cycles of obinutuzumab and chlorambucil …

Dermatological manifestations of hematologic neoplasms. Part II: nonspecific skin lesions/paraneoplastic diseases.

Cutaneous manifestations occur in the course of hematologic malignancies and precede, accompany or occur late in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, immunosuppression resulting from the hematologic disease itself or its treatment. The dermatologist must be aware of these conditions that may be helpful both in the diagnosis of the underlying disease and in reducing patient morbidity. This review (part II) addresses the paraneoplastic dermatological changes associated with systemic hematologic malignancies.

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… erythematous base | Others: pulse therapy with methylprednisolone, methotrexate, mycophenolate, colchicine, sulfasalazine, dapsone, minocycline, apremilast, thalidomide Immunobiologicals: infliximab, adalimumab, etanercept, ustekinumab Refractory disease: intravenous immunoglobulin, cyclophosphamide, chlorambucil … Slow evolution to large plaques. | Topical and systemic corticosteroids, thalidomide, high-dose intravenous immunoglobulin (IVIG), chlorambucil, among others Others: Non-Hodgkin's and Hodgkin's lymphoma, Waldenström’s macroglobulinemia, MDS, CLL Prurigo | Leukemia and Hodgkin's disease | Symmetrically …

Xanthoma-like Skin Changes in an Elderly Woman with a Normal Lipid Profile.

Dear Editor, An 83-year-old woman developed yellow-brownish infiltrates, nodules, and tumors mimicking xanthomas, mostly involving the perio … son and due to the rarity of the disease, the optimal therapy has not been not defined. Frequently, chlorambucil or melphalan have been used alone or in combination with prednisone (4). Treatment may result in remission of symptoms on the skin, but it does not provide a permanent cure (8). There are also single reports of the successful use of thalidomide, len …

Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody-Positive Primary Membranous Nephropathy.

IntroductionPrimary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN.MethodsPatients with newly diagnosed or relapsed PMN (cohort 1 [C1]; n = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; n = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point w

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… Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy N Engl J Med 310 1984 946 950 10.1056/NEJM198404123101503 6366560 21 Ponticelli C. Zucchelli P. Passerini P. … A randomized trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy N Engl J Med 320 1989 8 13 10.1056/NEJM198901053200102 2642605 22 Ponticelli C. Zucchelli P. Passerini P. …

EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies.

ObjectiveValue frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).MethodsHere we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. Th

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… Analysis of quality of life and well-being from the randomized phase 3 study of ibrutinib versus chlorambucil in older patients with treatment-naïve CLL (RESONATE-2TM). Clinical Lymphoma Myeloma and Leukemia 2016;16 10.1016/j.clml.2016.07.066 30. Goede V, Fischer K, Busch R, et al. … Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014;370:1101–10. 10.1056/NEJMoa1313984 31. Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. …

Immune mechanisms and immunomodulatory therapies in steroid-resistant nephrotic syndrome.

Steroid-resistant nephrotic syndrome (SRNS) is a complex and refractory kidney disease generally causing chronic kidney dysfunction, characterized by persistent proteinuria despite prolonged corticosteroid therapy. This review comprehensively explores the mechanisms of immunity driving SRNS, mainly focusing on the complex function network within immune cells, pro-inflammatory cytokines, and podocyte injury. Current immunosuppressive therapies show limited efficacy, prompting exploration of precision immunomodulatory strategies. Emerging approaches include IL-17 or low-dose IL-12 modulation, pr

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… Chlorambucil [ 37 , 40 ] | Alkylating agent that induces DNA damage and apoptosis in immune cells. | Limited use due to toxicity; historically used in steroid-resistant cases. | High risk of bone marrow suppression and long-term malignancy. … Alkylating agents (cyclophosphamide, chlorambucil) Alkylating agents, such as cyclophosphamide and chlorambucil, are applied in SRNS because of their potent immunosuppressive effects by inducing apoptosis of rapidly dividing immune cells [ 37 ]. …

Association Between Geriatric Assessment and Post-Chemotherapy Functional Status in Older Patients with Cancer.

BackgroundMaintaining functional status is among the most important patient-centered outcomes for older adults with cancer. This study investigated the association between comprehensive geriatric assessment (CGA) and progressive disease or decline of IADL-independence 1 year after chemotherapy, overall survival (OS), and premature termination of chemotherapy. CGA-based functional status and quality of life (QOL) 1 year after chemotherapy are also described.MethodsThis prospective cohort study involved patients aged ≥65 years treated with chemotherapy for any cancer type. CGA and the G8-screeni

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… cyclophosphamide + etoposide + vincristine + prednisone; R-CHOP, rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone; R-CVP, rituximab + cyclophosphamide + vincristine + prednisone; R-DHAP, rituximab + cisplatin + cytarabine + prednisone; R-PECC, rituximab + prednisone + etoposide + chlorambucil … R-bendamustine (1, 5, and 9 weeks, n = 3) Azacitidine (duration unknown, n = 3) R-DHAP (11 weeks, n = 1) Venetoclax (duration unknown, n = 1) Lymphoplasmacytic-/small B-cell lymphoma | 17 (14.8%) | Cyclophosphamide-based ( n = 14) h (median 21 weeks, IQR 17.8-22 weeks) R-bendamustine (20 & 21 weeks, n = 2) R-chlorambucil …