Obinutuzumab in the treatment of autoimmune haemolytic anaemia and immune thrombocytopenia in patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma

Herishanu, Yair; Levi, Shai; Kamdjou, Talia; Bornstein, Yotam; Ram, Ron; Benyamini, Noam; Varon, David; Avivi, Irit; Perry, Chava

doi:10.1111/bjh.17105

Cited by 7 publications

(8 citation statements)

References 12 publications

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“…Obinutuzumab, a third-generation humanized anti-CD20 therapy approved for CLL, has been suggested to achieve more effective depletion (compared with rituximab) not only of peripheral B cells but also in lymphoid tissue. 45 Here, obinutuzumab and chlorambucil were used as first-line treatment in our patient with CLL-MG, and therefore, we cannot derive a comparative statement regarding anti-CD20 therapies (as it has been done for other CLL-associated/autoimmune diseases, e.g., autoimmune hemolytic anemia, immune thrombocytopenia, 46 rheumatoid arthritis, 47 or anti-MAG neuropathy 48,49 ). Nevertheless, our patient with CLL-MG was successfully treated early on, and obinutuzumab and chlorambucil had lasting effects and were safe.…”

Section: Discussionmentioning

confidence: 99%

Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

Ingelfinger

Kramer

Lutz

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesMyasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates.MethodsWe identified patients with acetylcholine receptor antibody–positive (AChR+) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses. We generated recombinant monoclonal antibodies (mAbs) corresponding to the B-cell receptors of the CLL phenotype B cells and screened them for autoantigen binding.ResultsA computational immune cell screen revealed a subgroup of 5/38 patients with MG and 0/21 healthy controls who displayed a CLL-like B-cell phenotype. In follow-up hematologic flow cytometry, 2 of these 5 patients were diagnosed with an MBL. An additional patient with AChR+MG as a complication of manifest CLL presented at our neuromuscular clinic and was successfully treated with the anti-CD20 therapy obinutuzumab plus chlorambucil. We investigated the specificities of expanding CLL-like B-cell clones to assess a direct causal link between the 2 diseases. However, we observed no reactivity of the clones against the AChR, antigens at the neuromuscular junction, or other common autoantigens.DiscussionOur study suggests that AChR autoantibodies are produced by nonmalignant, polyclonal B cells The new anti-CD20 treatment obinutuzumab might be considered in effectively treating AChR+MG.Classification of EvidenceThis is a single case study and provides Class IV evidence that obinutuzumab is safe to use in patients with MG.

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Section: Discussionmentioning

confidence: 99%

Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

Ingelfinger

Kramer

Lutz

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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“…In the case of contraindications to GCs, their intolerance, lack of response or the need to quickly inhibit massive hemolysis, IVIG is used at a dose of 1 g/kg bw/day for two consecutive days [40,46]. Resistant forms are treated with rituximab (R) (four doses of 375 mg/m 2 weekly) with an overall response rate reported as 72-80% [47,48]. If the above-mentioned regimens remain ineffective, other immunosuppressants can be considered (cyclophosphamide, azathioprine, cyclosporine, and mycophenolate mofetil).…”

Section: Autoimmune Hemolytic Anemiamentioning

confidence: 99%

Autoimmune cytopenias in chronic lymphocytic leukemia: a growing challenge in targeted therapies?

2022

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“…In primary AIHA, corticosteroids (either prednisone or dexamethasone) achieve a 90% overall response rate (ORR). In patients who fail to respond or relapse quickly, anti-CD20 monoclonal antibodies can be given 120,123–125 . As discussed later, BTKis have shown to be effective as treatment for AIHA.…”

Section: Managementmentioning

confidence: 99%

Autoimmune Cytopenia in CLL

Albiol

Moreno

2021

Cancer J

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Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune hemolytic anemia and immune thrombocytopenia and, less frequently, with pure red cell aplasia and immune neutropenia. The emergence of these complications is related to an intertwined and complex relationship between patient, disease, and treatment characteristics. The prognostic repercussion of autoimmune cytopenia (AIC) in patients with CLL mainly depends on its response to therapy. For patients with AIC and nonactive CLL, treatment is as in primary, uncomplicated AIC, keeping in mind that no response is an indication for CLL therapy. The success of treating active CLL-related AIC widely relies on a flexible strategy that should include initial therapy with corticosteroids and a rapid shift to effective CLL therapy in nonresponding patients. Targeted therapies (e.g., ibrutinib) that have already demonstrated to be effective in CLL-related AIC will likely offer a unique possibility of treating both AIC and CLL as a single target.

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Obinutuzumab in the treatment of autoimmune haemolytic anaemia and immune thrombocytopenia in patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma

Abstract: Fig 1. (A) Timeline of haemoglobin levels of chronic lymphocytic leukaemia (CLL) patients with autoimmune haemolytic anaemia (AIHA) treated with obinutuzumab. (B) Timeline of platelet counts of CLL patients with immune thrombocytopenia (ITP) treated with obinutuzumab.

Cited by 7 publications

References 12 publications

Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

Autoimmune cytopenias in chronic lymphocytic leukemia: a growing challenge in targeted therapies?

Autoimmune Cytopenia in CLL

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