Haematol: Daratumumab may be used for multiple refractory autoimmune cytopenias

Immune thrombocytopenia (ITP) and warm autoimmune hemolytic anemia (AIHA) are antibody-mediated autoimmune diseases in which plasma cells secrete pathogenic antibodies against platelet and red blood cell antigens
.

Daratumumab is an anti-CD38 monoclonal antibody used to target tumor plasma cells in multiple myeloma.

Immune thrombocytopenia (ITP) and warm autoimmune hemolytic anemia (AIHA) are antibody-mediated autoimmune diseases in which plasma cells secrete pathogenic antibodies against platelet and red blood cell antigens

Table 1: Patient characteristics and results
.

Table 1: Patient characteristics and results
.

Figure 1: The evolution of autoimmune cytopenia after daratumumab treatment
.

(A) The evolution of platelet count in patients with immune thrombocytopenia after daratumumab treatment

Figure 1: The evolution of autoimmune cytopenia after daratumumab treatment .
(A) The evolution of platelet count in patients with immune thrombocytopenia after daratumumab treatment .
Patient #5 suffers from Glanzmann syndrome.
The red star indicates bleeding symptoms .
(B) The evolution of hemoglobin levels in patients with warm autoimmune hemolytic anemia after daratumomab .
Week 0 corresponds to the first daratumumab infusion (orange "D") .
CS: corticosteroid, CYC: cyclophosphamide; IVIG: intravenous immunoglobulin, MMF: mycophenolate mofetil, RBC: red blood cell infusion, SPL: splenectomy .

Eight patients (5 women [62.
5%]; median age 45 years [range, 34-70]) from six participating centers received daratumumab for refractory ITP (n=5), Acquired Glanzmann syndrome with pre-ITP and normal platelet count (n=1) or warm AIHA (n=2)
.

6 people have secondary ITP or warm AIHA, 5 people have Evans syndrome but no underlying immunodeficiency (including 1 patient with primary antiphospholipid syndrome), 1 patient has a history of Hodgkin’s lymphoma , Cured (#5) syndrome 9 years before the onset of ITP/Glanzmann ( Table 1 )

Table 1 Table 1

 The median platelet count of 5 patients with ITP was 11x10 ⁹/L (range, 0–21x10 ⁹/L), and all patients had skin and/or mucosal bleeding within one month before daretuzumab  treatment
.

Two patients (#1, #2) achieved complete remission at 4 weeks ( Figure 1 )

^{9 9} Figure 1

The patient (#3) was dependent on corticosteroids and did not respond at 4 weeks, which resulted in a brief increase in corticosteroid dose
.

However, even after discontinuing corticosteroids 24 weeks after starting daratumomab, he still achieved a lasting complete remission, indicating the delayed effect of anti-CD38 treatment

A 35-year-old patient (#5) has chronic ITP.
After splenectomy, despite a normal platelet count, he developed Acquired Glanzmann Platelet Asthenia with bleeding
.

She has anti-GPIIbIIIa antibodies, and platelet aggregation studies have shown that there is no aggregation with adenosine diphosphate, epinephrine or arachidonic acid, and has reverse ristomycin agglutination

The median baseline hemoglobin level of the two patients with warm AIHA was 9.
4 g/dL, the median reticulocyte count was 174× ^{10 9} /L, and the median bilirubin level was 27 mmol/L
.

The haptoglobin level of the two patients was <0.
1 mg/L, and the median lactate dehydrogenase level was 2.
8 times the normal range
.
Both have a history of ITP, but platelet counts were normal at the time of the first daratumumab infusion
.
One patient achieved complete remission after four cycles of daratumumab, but relapsed after 9 months, and the other patient did not remission after 11 cycles, although the need for blood transfusion gradually decreased after 3 months
.

⁹

Beginning with the first infusion of daratumumab, and after a median follow-up of 24 weeks, 5 patients experienced at least one moderate adverse event
.
Three people (#3, #7, and #8) had a mild reaction during the first daratumumab infusion
.
No further infusion-related reactions occurred afterwards
.
Two patients had an infection event: Patient (#5) had bacterial pneumonia and needed to be hospitalized at 4 weeks, and patient (#8) had COVID-19 pneumonia and needed hospitalization and convalescent plasma therapy, because at 20 weeks Symptoms persist at times
.
The median gamma globulin level decreased from 7.
1 g/L before treatment to 4.
2 g/L at week 12 and 6.
1 g/L at week 36
.
Of the 6 patients, 5 developed hypogammaglobulinemia at 12 weeks
.

Although this study has some limitations, including its uncontrolled design and patient heterogeneity, the results indicate that daratumomab may be effective in some patients with refractory ITP and/or warm AIHA.
Two diseases are associated with high mortality
.
The researchers observed rapid reaction's (within a month), indicating that four times Dare properly, especially monoclonal antibody responders infusion sufficient to induce remission , however, the best is yet to be determined number of infusion
.
Importantly, the two patients who initially had a complete remission eventually relapsed at 3 and 9 months, indicating that plasma cell remodeling occurred
.
In these patients, the ongoing autoimmune B cell response may not be affected by daratumomab, which targets plasma cells and retains CD38-negative B cells
.
Therefore, combining B cell depletion with anti-CD20 antibodies and daratumumab may impair the production of newly formed autoreactive plasma cells and prevent recurrence
.

Daratumumab may be effective for some patients with refractory ITP and/or warm AIHA.
These two diseases are associated with high mortality.
Infusion of subdaratumumab is sufficient to induce response and remission indicates the occurrence of plasma cells Reconstruction Combining depletion of B cells with anti-CD20 antibodies and daratumumab may impair the production of newly formed autoreactive plasma cells and prevent recurrence
.

In this particular group of immunocompromised patients, the risk of serious infections is a major problem
.
All but one experienced severe but transient hypogammaglobulinemia, and two developed symptomatic infections
.
Therefore, the risk/benefit balance of this type of treatment should be carefully discussed based on the patient's clinical history
.

The risk of serious infection is a major problem
.
All but one experienced severe but transient hypogammaglobulinemia, and two developed symptomatic infections
.
Therefore, the risk/benefit balance of this type of treatment should be carefully discussed based on the patient's clinical history
.

In conclusion, daratumomab may provide clinical benefit for patients with ITP or warm AIHA refractory to standard treatment
.
However, the efficacy seems to be relatively moderate, and hypogammaglobulinemia puts patients at risk of infection
.
Future prospective trials will evaluate the application of CD38-directed monoclonal antibodies in the treatment of patients with immune cytopenia
.

Daratumumab may provide clinical benefits for patients with ITP or mild AIHA refractory to standard treatment
.
However, the efficacy seems to be relatively moderate, and hypogammaglobulinemia puts patients at risk of infection
.
Future prospective trials will evaluate the application of CD38-directed monoclonal antibodies in the treatment of patients with immune cytopenia
.

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