Isatuximab and Iberdomide as Immunotherapy for High Risk in Smouldering Myeloma
The study will test a new combination of 3 drugs: Isatuximab (Isa), Iberdomide (Iber) and Dexamethasone (Dex), in patients who have intermediate or high risk smouldering myeloma. Smouldering myeloma is an early form of myeloma which may progress to active multiple myeloma, but at a slow rate. Patients with smouldering myeloma do not usually receive any treatment but will have regular check-ups and observation. Some patients have a diagnosis of smouldering myeloma which has a higher risk of progressing to active myeloma. The study will test if the combination of drugs is effective at preventing or delaying the disease progressing into active multiple myeloma. The study will also test if the combination is tolerated and accepted by patients.
• Able and willing to provide written informed consent and comply with protocol-mandated visits, treatment plan, laboratory tests and other study procedures.
• Age ≥ 18 years
• Diagnosed with smouldering myeloma (SMM) within 5 years of study registration AND diagnosed with intermediate or high risk SMM within 2 years of registration.:
‣ i.e. patients may have been diagnosed de novo with intermediate or high risk smouldering myeloma within 2 years of study registration OR
⁃ patients may have been diagnosed with low or low-intermediate smouldering myeloma within 5 years of study registration and then their risk classification has changed to intermediate or high risk within 2 years of study registration.
• Diagnosed with intermediate or high-risk SMM defined by IMWG diagnostic criteria and IMWG SMM risk stratification. Intermediate or high risk is defined by the presence of 2 or more of the following factors:
‣ BM plasma cell infiltrate \>20%
⁃ Serum paraprotein \>20g/l
⁃ Serum Free Light Chain (SFLC) Ratio \>20 (but \<100)
⁃ Presence of t(4;14), t(14;16), del 17p, del 13q or 1q gain by fluorescence in situ hybridization (FISH) studies. Copy number abnormalities will be considered significant if present in ≥ 20% of cells.
• Measurable disease with at least one of the following:
‣ Paraprotein ≥5g/L
⁃ Serum free light chains ≥100mg/L with abnormal light chain ratio
⁃ Bence Jones protein ≥200mg/24hr
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 3 x ULN (if ALT and AST are tested, both must meet this criteria)
• Adequate marrow function:
‣ Neutrophils ≥1.0 x109/L (unless the participant has a known/suspected diagnosis of familial or racial neutropenia in which case an ANC ≥0.75 x 109/L is allowed),
⁃ Haemoglobin (Hb) ≥ 100g/L
⁃ Platelets ≥ 75 ×109/L
⁃ Creatinine clearance (CrCl) ≥ 30 mL/minute, according to the Cockcroft-Gault formula, following correction of reversible causes (e.g. dehydration, hypercalcaemia, sepsis)
⁃ Willing to comply with the contraceptive requirements of the trial