ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance for Transplant-Eligible Primary Plasma Cell Leukemia

A Prospective, Single-Arm, Phase II Study of Autologous Stem Cell Transplantation Combined With BCMA CAR-T Therapy Followed by GPRC5D/CD3 Bispecific Antibody Maintenance in Transplant-Eligible Patients With Primary Plasma Cell Leukemia

This is a prospective, single-arm, phase II study to evaluate the efficacy and safety of autologous stem cell transplantation combined with BCMA CAR-T therapy followed by GPRC5D/CD3 bispecific antibody maintenance in transplant-eligible patients with primary plasma cell leukemia.

All subjects will receive standard induction therapy for up to four cycles prior to screening. Following response evaluation, those who meet the inclusion criteria will be enrolled. Enrolled patients will undergo autologous stem cell transplantation (ASCT) combined with BCMA CAR-T cell therapy, followed by GPRC5D/CD3 bispecific antibody therapy.

Patients who achieve a stringent complete response (sCR) and sustained MRD negativity (≥12 months) will receive maintenance therapy for 24 months, and may then enter a treatment-free observation phase. Patients who experience MRD resurgence or loss of response during observation will resume maintenance therapy.

Patients who do not achieve both sCR and sustained MRD negativity (≥12 months) will continue GPRC5D/CD3 bispecific antibody therapy until disease progression or unacceptable toxicity.

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 70 years.
2. Participants with documented newly-diagnosed primary plasma cell leukemia according to IMWG diagnostic criteria.
3. Measurable disease at screening, defined as: Serum M-protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
4. Patients deemed eligible for high-dose chemotherapy with ASCT.
5. Tumor cells were BCMA and GPRC5D positive.
6. Serum total bilirubin <2 x upper limit of normal (ULN), serum AST and ALT <3 x ULN, creatinine clearance ≥ 30mL/min (Cockroft-Gault formula).
7. Informed Consent/Assent: All subjects have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

1. Active amyloidosis.
2. Central nervous system involvement.
3. Prior BCMA-targeted therapy or CAR-T therapy.
4. Active hepatitis B or hepatitis C virus infection.
5. Known HIV infection.
6. Life expectancy <6 months.
7. Woman who are pregnant or breastfeeding
8. Evidence of uncontrolled dysfunction of heart, lung, brain, and other important organs.
9. Any other conditions that are not eligible for the trial in the judgement of the principal investigator.