Overview
This study investigates whether raising blood levels of beta-hydroxybutyrate (BHB) - a natural molecule produced by the body during fasting or a low-carbohydrate diet - is safe and feasible and can improve the effectiveness of immunotherapy in patients with multiple myeloma, while remaining safe and well-tolerated. Patients will be randomly assigned to one of four intervention groups or a control group. The intervention groups will either follow a ketogenic diet (less than 10% of calories from carbohydrates) or receive oral supplementation with deltaG® Ketone Monoester Performance \[(R)-3-hydroxybutyl (R)-3-hydroxybutyrate; CAS 1208313-97-6; TdeltaS Global, Inc., Oxford, UK\], administered orally three times daily at either a low dose (13.5 g per serving, 40.5 g/day) or a high dose (25 g per serving, 75 g/day), in accordance with the FDA GRAS-approved dosing range. The control group will receive standard nutritional care. The study includes two parts: Part A enrolls patients receiving bispecific antibody treatment, and Part B enrolls patients receiving CAR-T cell therapy. Both dosing levels are applied in each part.
Eligibility
Inclusion Criteria:
- Multiple Myeloma with indication for CAR-T cell therapy with Ciltacabtagene autoleucel (target antigen: BCMA) or a BCMA-directed bispecific antibody (e.g., Teclistamab, Elranatamab, Linvoseltamab).
- Age ≥18 years on the day the informed consent is signed.
Exclusion Criteria:
- Active infection requiring systemic therapy.
- Known history of infection with Human Immunodeficiency Virus (HIV) or Hepatitis.
- Significant short-term weight loss (\>10% within the last 6 weeks).
- ECOG Performance Status ≥2.
- Prior immunoeffector cell therapy (CAR-T cell therapy or bispecific antibodies).
- Active immunosuppression due to another condition (e.g., autoimmune disease, second malignancy).
- Very high tumor burden with high risk for tumor lysis syndrome, as determined by myeloma-specific markers or markedly elevated LDH (per the treating myeloma team).
- Women of childbearing potential in whom pregnancy cannot be reliably excluded prior to study entry.
