BEAM-MM - β-Hydroxybutyrate-Enhanced Adaptive Immunity in Multiple Myeloma

Universitätsklinikum Hamburg-Eppendorf45 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Multiple Myeloma (MM)CAR T Cells

Interventions

Ketogenic dietBEHAVIORAL

Induction of a stable ketogenic metabolic state to increase blood BHB levels in order to improve T-cell function through immunometabolic reprogramming. Duration: 4 weeks (28 days) Macronutrient distribution: * Carbohydrates: \<10% of daily caloric intake (approx. 20-30 g/day) * Fats: 70-75% of daily caloric intake * Proteins: 15-20% of daily caloric intake

Ketogenic DrinksBEHAVIORAL

Ketone Performance, DeltaG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Safety and Tolerability

No occurrence of Cytokine Release Syndrome (CRS) Grade ≥3 or neurotoxicity (ICANS) Grade ≥3, AND completion of the full 28-day intervention in ≥80% of participants per arm (≥4/5 per arm).

Time frame: Day 0 to 28 of the intervention

CAR-T-Cell Expansion

Number of CAR-T-Cells per ml of blood

Time frame: Day 7 after infusion

Effector Cytokines

Protein abundance per ml of blood or cytokines signature of effector cells

Time frame: Day 1 or 3 after bispecfiic antibody treatment