Iberdomide vs. Iberdomide Plus Isatuximab Maintenance Therapy Post ASCT in Newly Diagnosed Multiple Myeloma

Inclusion Criteria:

• Prior inclusion and treatment within the GMMG-HD8 / DSMM XIX trial

• Received at least one cycle high dose melphalan therapy (HDM) and autologous stemcell transplantation (ASCT)

• At least Partial Response (PR) according to IMWG criteria at inclusion in the trial

• Age of at least 18 years at trial inclusion

• WHO performance status of 0, 1, or 2

• Negative pregnancy test at inclusion (women of childbearing potential)

• For all men and women of childbearing potential: patients must be willing andcapable to use adequate contraception during the complete therapy

• Ability of patient to understand character and individual consequences of theclinical trial

• Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

• Subjects with gastrointestinal disease that may significantly alter the absorptionof iberdomide

• Patient has known hypersensitivity (or contraindication) to any of the components ofstudy therapy that are not amenable to premedication with steroids or H1 blockersand that would prohibit further treatment with these agents (e.g. known intoleranceor hypersensitivity to infused proteins products, sucrose, histidine, andpolysorbate 80 as well as intolerance to arginine and Poloxamer 188)

• Patients with a history of serious allergic reaction to another immunomodulatoryagent (thalidomide, lenalidomide, or pomalidomide)", as angioedema and severedermatologic reactions, including Grade 4 rash and exfoliative or bullous rash

• Patients currently being treated with strong inhibitors or inducers of CYP3A4/5

• Systemic AL amyloidosis (except for localized AL amyloidosis limited to the skin orthe bone marrow), plasma cell leukemia or polyneuropathy, organomegaly,endocrinopathy, monoclonal-protein and skin abnormalities or Waldenströmmacroglobulinemia.

• Previous systemic anti-myeloma treatment other than administered within the GMMG-HD8 / DSMM XIX trial (including up to two cycles cycle high dose melphalan therapy (HDM)and autologous stem cell transplantation (ASCT). Local, consolidative radiotherapyfor myeloma disease is permitted unless performed in case of progressive diseaseaccording to IMWG criteria

• Severe cardiac dysfunction (NYHA classification III-IV)

• Significant hepatic dysfunction (ASAT and/or ALAT ≥ 3 times normal level and/orserum bilirubin ≥ 1.5 times normal level if not due to hereditary abnormalities asGilbert's disease), unless related to MM or HDM/ASCT.

• Patients with active or uncontrolled hepatitis B or C or detectable liver diseasedue to hepatitis B or C. In case of history of hepatitis B or C, it must beclarified whether it has been overcome and negative circulating HBV-DNA or HCV-RNAmust be provided. Positive hepatitis B status may only be acceptable in absence ofcirculating HBV-DNA or signs of chronic or acute infection and if an adequateprophylaxis is being implemented during the course of the study. Prophylaxis forpatients with history of hepatitis B or C should be set on a patient individualbasis.

• HIV positivity

• Patients with active, uncontrolled infections

• Patients with severe renal insufficiency (Creatinine Clearance < 30ml/min) orrequiring hemodialysis

• Patients with peripheral neuropathy or neuropathic pain, grade 2 or higher (asdefined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE,version 5.0)

• Patients with a history of any active malignancy during the past 5 years with theexception of following malignancies after curative therapy: basal cell carcinoma ofthe skin, squamous cell skin carcinoma, stage 0 cervical carcinoma or any in situmalignancy. A history of an early stage malignancy during the past 5 years may beacceptable, however, in this case the GMMG study office has to be consulted prior tostudy inclusion

• Patients with acute diffuse infiltrative pulmonary and/or pericardial disease

• Autoimmune haemolytic anaemia with positive indirect Coombs test or immunethrombocytopenia

• Platelet count < 75 x 109/l

• Haemoglobin ≤ 8.0 g/dl, unless related to MM

• Absolute neutrophil count (ANC) < 1.0 x 109/l (the use of colony stimulating factorswithin 14 days before the test is not allowed)

• Corrected serum calcium > 14 mg/dl (> 3.5 mmol/l)

• Unable or unwilling to undergo thromboprophylaxis

• Pregnancy and lactation

• Participant has any concurrent severe and/or uncontrolled medical condition orpsychiatric disease that is likely to interfere with study procedures or results, orthat in the opinion of the investigator would constitute a hazard for participatingin this study or that confounds the ability to interpret data from the study

• Subjects, who are committed to an institution by virtue of an order issued either bythe judicial or the administrative authorities

• Participation in other interventional clinical trials. This does not includelong-term follow-up periods without active drug treatment of previous studies duringthe last 6 months.