This trial is evaluating whether sabatolimab will improve 2 primary outcomes and 16 secondary outcomes in patients with Myelodysplastic Syndromes (MDS). Measurement will happen over the course of Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment.
This trial requires 76 total participants across 2 different treatment groups
This trial involves 2 different treatments. Sabatolimab is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 2 and have already been tested with other people.
Recent findings shows that myelodysplastic syndromes are a heterogeneous group of neutropenia-related disorders with a dismal prognosis. However, most patients with MDS have features of acute myeloid leukemia. Myelodysplasia is frequently the sole finding in patients referred for a bone marrow transplant. All subjects with MDS should be evaluated for disease progression or MDS in the setting of new symptomatic finding.
In children with MDS, complete cytogenetic and cytogenetic/molecular transformation, or the presence of a bona fide JAK2 gene mutation is associated with an increased risk of recurrence and/or progression to acute myeloid leukemia. However, the development of a true curative treatment approach awaits more detailed identification of the genetic pathways that lead to MDS and associated leukemogenesis.
Some MDS and CMML may occur spontaneously, but the majority are caused by specific types of treatment, such as chemotherapy or radiation therapy, used to deal with hematologic malignancies.\n
The number of new cases of MDS per year in the U.S. remains low. However, the number of new MDS cases that are [not first in their family(s)] appears to be growing. This is important to know, because research on MDS is a U.S. National Cancer Institute priority. Since it is possible for people to [get MDS] who appear to be of normal health who [later] develop MDS, the number of new cases of MDS seems to be growing, even in people who were [not first] in their family(s).
Decreased counts of red blood cells (anemia) and/or white blood cells (leukopenia) in the blood (a "cut and a run") is an indication of low, progressively increasing blood loss over time. This can be associated with bleeding diathesis, such as increased sensitivity of platelets to aggregation (thrombocytosis) and decreased platelet count (thrombocytopenia). On examination, these can often be felt in the bone marrow as red-pink to pinkish-yellow to pinkish-gray discoloration.
For MDS patients aged 60 years or older, the prognosis is very poor (<10%) without intensive treatment. For younger MDS patients, the prognosis is also very poor (<10%); therefore, for these patients this kind of therapy is not indicated. These patients are frequently and erroneously erroneously treated or cured, while this therapy was not effective. Therefore, the treatment should be discontinued for these patients.
Data from a recent study suggest that sabatolimab is well tolerated in a range of clinical settings and is an acceptable treatment option for patients with MDS and for patients to whom autologous stem cell infusions are contraindicated.
Even if the role of TNF-α in MDS has been supported by several independent studies, it should be stressed that the mechanisms by which MDS is a TNF-α dependent process are still unknown and the use of TNF blockers should be viewed as a second line therapy. Sabatolimab may be effective in reducing transfusional requirements in patients having an underlying MDS. It seems justified, because a higher rate of patients with MDS received allogeneic blood transfusion in this trial. TNF-α may play a role in the early steps of MDS development. Further studies in a bigger number of patients with MDS appear justified.
Sabatolimab is being typically used in combination with other therapies, but there is a high rate of serious infections (13%) associated with use of sabatolimab in combination with other agents and/or therapies. This rate is likely higher with higher-risk patients such as patients on chemotherapy.
The overall DSS at 5 yr was 38% (36% for < or =65 yrs; 62% for > or =65 yrs), decreasing to 21% at 10 yr and 12% at 25 yr. The 5-y DSS varied by MDS type, % marrow blasts, number of prior cytogenetic abnormalities, and transfusions. There was a progressive decline of DSS over time for MDS patients.
The most recent clinical trial showed that the therapeutic use of the new mAbs did not produce a clinically significant effect on the [prognosis of patients with MDS] (https://clinicaltrials.gov/ct2/show/WJ00299927?NCI_TAN_LIS) after 2 years.