Daratumumab monotherapy in refractory warm autoimmune hemolytic anemia and cold agglutinin disease

Autoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment. Daratumumab, a monoclonal antibody targeting CD38, could be beneficial by suppression of CD38+ plasma cells and thus autoantibody secretion. In addition, because CD38 is also expressed by activated T cells, daratumumab may also act via immunomodulatory effects. We evaluated the efficacy and safety of daratumumab monotherapy in an international retrospective study including 19 adult patients with heavily pretreated refractory AIHA. In warm AIHA (wAIHA, n = 12), overall response was 50% with a median response duration of 5.5 months (range, 2-12), including ongoing response in 2 patients after 6 and 12 months. Of 6 nonresponders, 4 had Evans syndrome. In cold AIHA (cAIHA, n = 7) overall hemoglobin (Hb) response was 57%, with ongoing response in 3 of 7 patients. One additional patient with nonanemic cAIHA was treated for severe acrocyanosis and reached a clinical acrocyanosis response as well as a Hb increase. Of 6 patients with cAIHA with acrocyanosis, 4 had improved symptoms after daratumumab treatment. In 2 patients with wAIHA treated with daratumumab, in whom we prospectively collected blood samples, we found complete CD38+ T-cell depletion after daratumumab, as well as altered T-cell subset differentiation and a severely diminished capacity for cell activation and proliferation. Reappearance of CD38+ T cells coincided with disease relapse in 1 patient. In conclusion, our data show that daratumumab therapy may be a treatment option for refractory AIHA. The observed immunomodulatory effects that may contribute to the clinical response deserve further exploration.</p

High frequency of central nervous system involvement in transformed Waldenstrom macroglobulinemia

Histologicaltransformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a rare event in Waldenström macroglobulinemia (WM) and is associated with a poor prognosis.1-4 It confers an inferior outcome compared with WM patients without HT.2,3 Most transformed WM patients present with elevated serum lactate dehydrogenase (LDH) levels and extranodal disease.1 Among extranodal sites, the central nervous system (CNS) is one of the most frequently involved sites identified at diagnosis of transformed WM (ranging from 13% to 18%).1,3 However, the prognostic value of CNS involvement is unknown, and the rate of CNS involvement at relapse has not been previously reported in this setting.This work was supported by Cancer Research UK [C355/A26819], FC AECC, and AIRC under the “Accelerator Award Program” [EDITOR] to M.A. and R.G.-S

Polyneuropathy Associated with IgM Monoclonal Gammopathy; Advances in Genetics and Treatment, Focusing on Anti-MAG Antibodies

With increasing age, the chances of developing either MGUS or polyneuropathy increase as well. In some cases, there is a causative relationship between the IgM M-protein and polyneuropathy. In approximately half of these cases, IgM targets the myelin-associated glycoprotein (MAG). This results in chronic polyneuropathy with slowly progressive, predominantly sensory neurological deficits and distally demyelinating features in nerve conduction studies. Despite the disease being chronic and developing slowly, it can cause considerable impairment. We reviewed English medical publications between 1980 and May 2022 on IgM gammopathy-associated polyneuropathy, with special attention to studies addressing the pathophysiology or treatment of anti-MAG polyneuropathy. Treatment options have been limited to a temporizing effect of intravenous immunoglobulins in some patients and a more sustained effect of rituximab but in only 30 to 55 percent of patients. An increase in our knowledge concerning genetic mutations, particularly the MYD88L265P mutation, led to the development of novel targeted treatment options such as BTK inhibitors. Similarly, due to the increasing knowledge of the pathophysiology of anti-MAG polyneuropathy, new treatment options are emerging. Since anti-MAG polyneuropathy is a rare disease with diverse symptomatology, large trials with good outcome measures are a challenge

A mixed exercise training programme is feasible and safe and may improve quality of life and muscle strength in multiple myeloma survivors

Exercise programmes are beneficial for cancer patients however evidence is limited in patients with multiple myeloma (MM), a cancer that is characterised by osteolytic bone disease, giving rise to high levels of bone morbidity including fractures and bone pain

Bendamustine plus rituximab for the treatment of Waldenström Macroglobulinaemia: patient outcomes and impact of bendamustine dosing

Bendamustine and rituximab (BR) therapy is commonly used in the treatment of Waldenström Macroglobulinaemia (WM). The impact dose of Bendamustine dose on response and survival outcomes is not well established, and the impact of its use in different treatment settings is not clear. We aimed to report response rates and survival outcomes following BR, and clarify the impact of depth of response and bendamustine dose on survival. A total of 250 WM patients treated with BR in the frontline or relapsed settings were included in this multicentre, retrospective cohort analysis. Rates of partial response (PR) or better differed significantly between the frontline and relapsed cohorts (91.4% vs 73.9%, respectively; p<0.001). Depth of response impacted survival outcomes: two-year predicted PFS rates after achieving CR/VGPR vs PR were 96% vs 82%, respectively (p=0.002). Total bendamustine dose was predictive of PFS: in the frontline setting, PFS was superior in the group receiving ≥1000mg/m2 compared with those receiving 800-999mg/m2 (p=0.04). In the relapsed cohort, those who received doses of <600mg/m2 had poorer PFS outcomes compared with those who received ≥600mg/m2 (p=0.02). Attaining CR/VGPR following BR results in superior survival, and total bendamustine dose significantly impacts response and survival outcomes, in both frontline and relapsed settings. This article is protected by copyright. All rights reserved