Therapeutic outcomes using subcutaneous low dose alemtuzumab for acquired bone marrow failure conditions

Thota, Swapna; Patel, Bhumika J.; Sadaps, Meena; Balasubramanian, Suresh Kumar; Sanikommu, Srinivasa Reddy; Hirsch, Cassandra M.; Marotta, Serena; Sekeres, Mikkael A.; Risitano, Antonio M.; Maciejewski, Jaroslaw P.

doi:10.1111/bjh.14907

Cited by 10 publications

(6 citation statements)

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“…Assuming that the latter forms are rare, salvage IST agents include campath and ATG. Campath has been effective in autoimmune disorders and in T-LGL, 40 – 42 thus, we and others treat aPRCA with this drug, 43 , 44 using low-dose subcutaneous regimens to limit infectious complications. Our experience with campath in aPRCA has shown that it yields the highest number of meaningful responses in patients, including those refractory to CTX or CsA and those who could not tolerate calcineurin inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Rational management approach to pure red cell aplasia

et al. 2017

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Pure red cell aplasia is an orphan disease, and as such lacks rationally established standard therapies. Most cases are idiopathic; a subset is antibody-mediated. There is overlap between idiopathic cases and those with T-cell large granular lymphocytic leukemia, hypogammaglobulinemia, and low-grade lymphomas. In each of the aforementioned, the pathogenetic mechanisms may involve autoreactive cytotoxic responses. We selected 62 uniformly diagnosed pure red cell aplasia patients and analyzed their pathophysiologic features and responsiveness to rationally applied first-line and salvage therapies in order to propose diagnostic and therapeutic algorithms that may be helpful in guiding the management of prospective patients, 52% of whom were idiopathic, while the others involved large granular lymphocytic leukemia, thymoma, and B-cell dyscrasia. T-cell-mediated responses ranged between a continuum from polyclonal to monoclonal (as seen in large granular lymphocytic leukemia). During a median observation period of 40 months, patients received a median of two different therapies to achieve remission. Frequently used therapy included calcineurin-inhibitors with a steroid taper yielding a first-line overall response rate of 76% (53/70). Oral cyclophosphamide showed activity, albeit lower than that produced by cyclosporine. Intravenous immunoglobulins were effective both in parvovirus patients and in hypogammaglobulinemia cases. In salvage settings, alemtuzumab is active, particularly in large granular lymphocytic leukemia-associated cases. Other potentially useful salvage options include rituximab, anti-thymocyte globulin and bortezomib. The workup of acquired pure red cell aplasia should include investigations of common pathological associations. Most effective therapies are directed against T-cell-mediated immunity, and therapeutic choices need to account for associated conditions that may help in choosing alternative salvage agents, such as intravenous immunoglobulin, alemtuzumab and bortezomib.

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Section: Discussionmentioning

confidence: 99%

Rational management approach to pure red cell aplasia

et al. 2017

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“…Almost all sporadic aplastic anemia, especially when severe and acute, appears to be immune-mediated. The strongest, most relevant evidence for an immune mechanism is the response of blood counts to a variety of immunosuppressive therapies and dependence of counts after recovery on maintenance calcineurin inhibitors 14,15 . Immune aplastic anemia lies in a spectrum of bone marrow and blood cell diseases (Figure 2A).…”

Section: Pathophysiologiesmentioning

confidence: 99%

Aplastic Anemia

2018

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“…One explanation could be our specific SC administration regimen. In a trial evaluating the efficacy of alemtuzumab in patients with marrow failure of single or multiple lineages, SC dose‐escalating administration of alemtuzumab over 4–5 days, with a total dose of 103 mg in SAA patients, produced a 58% response rate 22 ; some patients were also given long‐term maintenance “boosters” of alemtuzumab every 2–8 weeks 26 . In patients with other hematologic disorders, both IV and SC alemtuzumab have been used interchangeably; MDS (64% response using same dosing regimen as our study), 27 hemophagocytic lymphohistiocytosis (64% response), 28 and chronic lymphocytic leukemia (54%–87% response) 23,29 .…”

Section: Discussionmentioning

confidence: 99%

Alemtuzumab in relapsed immune severe aplastic anemia: Long‐term results of a phase II study

et al. 2023

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Immune severe aplastic anemia (SAA) is characterized by pancytopenia and immune‐mediated bone marrow destruction. SAA may be treated with hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). However, 30% of patients treated with IST relapse. We previously reported a clinical trial of alemtuzumab in which more than half of 25 relapsed SAA patients (56%) responded hematologically. Here, we present long‐term results of a total of 42 patients. Participants with SAA who had previously completed antithymocyte globulin (ATG)‐based IST, but had relapsed, were enrolled on this study. Alemtuzumab was administered intravenously (IV) (n = 28) or subcutaneously (SC) (n = 14). The primary endpoint was hematologic response at 6 months. Secondary endpoints included relapse, clonal evolution, and survival. This trial was registered at http://clinicaltrials.gov (NCT00195624). Patients were enrolled over 9 years, with median follow‐up of 6 years. Median age was 32 years, with 57% being female. At 6 months, 18 patients (43%) achieved response; 15 (54%) of those who received IV compared with 3 (21%) who received SC therapy. Six patients (14%) had durable long‐term response without need for subsequent AA‐directed therapy or HSCT at last follow‐up. Nine patients had clonal evolution, with high‐risk evolution occurring in 6. Overall survival was 67% at median follow‐up of 6 years. Prolonged iatrogenic immunosuppression was observed as long as 2 years after alemtuzumab administration. Alemtuzumab induces responses in relapsed SAA, some of which are durable long‐term. However, immunosuppression can persist for years, requiring long‐term monitoring.

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Therapeutic outcomes using subcutaneous low dose alemtuzumab for acquired bone marrow failure conditions

Cited by 10 publications

References 10 publications

Rational management approach to pure red cell aplasia

Rational management approach to pure red cell aplasia

Aplastic Anemia

Alemtuzumab in relapsed immune severe aplastic anemia: Long‐term results of a phase II study

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