QLS4131 plus isatuximab for newly diagnosed primary plasma cell leukemia

Inclusion Criteria

1. Participants must understand the study requirements and voluntarily provide written informed consent.
2. Age between 18 and 75 years.
3. Newly diagnosed primary plasma cell leukemia (pPCL) according to International Myeloma Working Group (IMWG) criteria, defined as malignant plasma cells accounting for ≥5% of circulating leukocytes on a peripheral blood smear or an absolute circulating malignant plasma cell count \>2 × 10\^9/L. Patients who have received no more than one cycle of prior anti-myeloma therapy are eligible.
4. Measurable disease meeting at least one of the following criteria:

   * Serum M-protein ≥10 g/L by serum protein electrophoresis (SPEP). For IgA- or IgD-type disease, quantitative IgA or IgD levels may be used.
   * Urinary M-protein ≥200 mg/24 hours.
   * If serum and urine M-protein levels do not meet these criteria, an abnormal serum free light chain (FLC) ratio (normal range: 0.26-1.65) with an involved serum FLC level ≥100 mg/L.
5. Adequate hepatic function, defined as total bilirubin \<1.5 × the upper limit of normal (ULN), except for patients with Gilbert syndrome, for whom total bilirubin must be \<3 × ULN; and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN.
6. Creatinine clearance ≥30 mL/min, calculated using the Cockcroft-Gault formula.
7. Hematologic parameters within seven days before screening assessment meeting the following criteria: white blood cell count ≥1.5 × 10\^9/L, absolute neutrophil count ≥1.0 × 10\^9/L, hemoglobin ≥70 g/L, and platelet count ≥50 × 10\^9/L; or considered eligible by the investigator based on the clinical circumstances.
8. For patients receiving hematopoietic growth factor support, including erythropoietin, G-CSF, GM-CSF, thrombopoietin receptor agonists, or other platelet-stimulating agents, at least two weeks must elapse between the last administration and screening assessment.
9. For patients receiving blood product transfusions, at least two weeks must elapse between the last red blood cell transfusion and screening hemoglobin assessment, and at least one week between the last platelet transfusion and screening platelet assessment.
10. Participants must be able to receive the recommended prophylactic anticoagulation therapy.
11. Women of childbearing potential must have a negative serum pregnancy test at screening and agree to use effective contraception from the time of informed consent throughout study treatment and for three months after the last dose of study treatment. Male participants, including those who have undergone vasectomy, must agree to use condoms during sexual intercourse with women of childbearing potential and must have no intention of fathering a child during the same period.

Exclusion Criteria

1. Diagnosis of smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, Waldenström macroglobulinemia, POEMS syndrome, amyloidosis, or secondary plasma cell leukemia.
2. Central nervous system involvement or clinical evidence of meningeal involvement.
3. Known intolerance, hypersensitivity, or contraindication to QLS4131 or isatuximab.
4. Severe or uncontrolled cardiovascular disease, including unstable angina, symptomatic congestive heart failure, myocardial infarction within six months before enrollment, severe uncontrolled arrhythmia, or other cardiovascular or cerebrovascular conditions considered unsuitable for participation by the investigator.
5. Active infections, including HIV infection, active hepatitis B (positive HBV DNA), active hepatitis C (positive HCV RNA), active or latent syphilis infection (positive Treponema pallidum antibody), active pulmonary tuberculosis indicated by chest imaging or other relevant tests within three months before or during screening, or other infections considered unsuitable for participation by the investigator.
6. Concurrent malignancy or serious concomitant disease that, in the investigator's opinion, may compromise participant safety or interfere with study completion.
7. Pregnant or breastfeeding women.
8. Life expectancy of less than six months.
9. Active gastrointestinal disorders that impair the ability to swallow tablets or may interfere with the absorption of study medications.
10. Major surgery requiring general anesthesia within two weeks before enrollment, incomplete recovery from major surgery, or planned major surgery during study participation. Kyphoplasty or vertebroplasty is not considered major surgery. Procedures under local anesthesia are permitted.
11. Receipt of a live attenuated vaccine within four weeks before the first administration of study treatment.
12. Active severe psychiatric illness, medical condition, or other circumstances that, in the investigator's judgment, may interfere with treatment, protocol compliance, or the ability to provide informed consent.
13. Inability or unwillingness to provide written informed consent.
14. Any other condition that, in the investigator's opinion, makes the participant unsuitable for enrollment.