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SL-401 Shows Promise in Advanced Myeloproliferative Neoplasms, Including CMML

• SL-401, a targeted therapy directed at the interleukin-3 receptor (CD123), demonstrates encouraging activity in advanced, high-risk myeloproliferative neoplasms (MPN). • The Phase II trial of SL-401 includes patients with chronic myelomonocytic leukemia (CMML), showing initial dosing is well-tolerated with no unexpected toxicities. • Researchers aim to improve blood counts, reduce transfusion dependency, alleviate symptoms, and achieve overall and complete responses with SL-401 treatment. • CD123, the target of SL-401, is overexpressed in MPN cells and microenvironmental immune cells, specifically plasmacytoid dendritic cells (pDCs), in the bone marrow.

SL-401, a novel targeted therapy, is showing promising results in a Phase II trial for patients with advanced, high-risk myeloproliferative neoplasms (MPN), including chronic myelomonocytic leukemia (CMML). The study, evaluating the activity of SL-401, offers hope for improved outcomes in this challenging patient population.

Targeting CD123 in MPNs

SL-401 is designed to target the interleukin-3 receptor (CD123), which is overexpressed in many hematologic malignancies. According to Mrinal Patnaik, MBBS, a hematologist at Mayo Clinic, CD123 is expressed not only on MPN cells but also on microenvironmental immune cells, specifically plasmacytoid dendritic cells (pDCs), found in the bone marrow of some CMML patients.

Initial Tolerability and Potential Benefits

Initial dosing of SL-401 has been well-tolerated in patients with MPN and CMML, with no unexpected toxicities observed to date. The therapeutic goal is to improve patients' blood counts, reduce their dependence on transfusions, and alleviate disease-related symptoms. Furthermore, researchers are striving to achieve both overall and complete responses with this treatment approach.

Clinical Implications

The development of SL-401 represents a significant step forward in addressing the unmet needs of patients with advanced MPNs and CMML. By targeting CD123, this therapy has the potential to disrupt the growth and survival of malignant cells, offering a new avenue for treatment in these complex hematologic disorders.
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Reference News

[1]
Dr. Patnaik on Activity of SL-401 in Chronic ...
onclive.com · Dec 30, 2016

SL-401, targeting CD123 overexpressed in hematologic malignancies, shows promise in a phase II trial for advanced MPN an...

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