Elranatamab/Lenalidomide Consolidation and/or Elranatamab Maintenance Versus Standard of Care After D-VRd Induction in Transplant-eligible NDMM Patients

Exclusion Criteria34

• Subjects previously treated with any systemic therapy for multiple myeloma. Patients are allowed corticosteroids during screening not \>160 mg of dexamethasone (or equivalent). Patients with concurrent radiotherapy (localized) within the 14 days before initiating induction therapy are not eligible (If possible, in these cases, enrolment should be deferred).
• Subject with ongoing Grade ≥ 3 peripheral sensory or motor neuropathy.
• Subject with history of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
• Subject with a current diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma.
• Subject has a diagnosis of Waldenström's macroglobulinemia, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
• The subject has had plasmapheresis within 14 days of initiating induction therapy.
• Subject with clinical signs of meningeal involvement of multiple myeloma.
• The subject has plasma cell leukemia (by WHO criterion: ≥5% of plasma cells in the peripheral blood) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• Subject has any concurrent medical or psychiatric condition or disease (e.g., active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
• Subject has clinically significant cardiac disease, including:
• • Subject has had myocardial infarction within 1 year before initiating induction therapy, or currently has an unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association \[NYHA\] class III IV).
• • Subject has uncontrolled cardiac arrhythmia (common terminology criteria for adverse events \[CTCAE\] version 4 grade ≥2) or clinically significant electrocardiography (ECG) abnormalities.
• • Subject with a baseline QT interval as corrected by Fridericia's formula (QTcF) \>470 msec (12-lead ECG).
• Subjects taking systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort (millepertuis) within the 14 days before initiating induction therapy.
• Known intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
• Known allergies to any of the study medications, their analogues, or excipients in the various formulations.
• Subjects who have had major surgery within 2 weeks before study inclusion (signing of the informed consent) OR will not have fully recovered from surgery before initiating induction therapy OR have surgery planned during their study participation. Kyphoplasty and vertebroplasty are not considered as major surgery.
• Subjects with any prior or concurrent invasive malignancy (other than multiple myeloma) within 10 years of study inclusion study, except for adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or localized prostate adenocarcinoma diagnosed ≥3 years ago and without evidence of biological failure, or other cancers for which the subject has undergone potentially curative therapy and has without evidence of relapse/recurrence for ≥10 years.
• Pregnant or breast-feeding women.
• Women that refuse to abstain from heterosexual intercourse or refuse to use adequate contraceptives during heterosexual intercourse starting at least 4 weeks before initiating induction therapy and continually until at least 4 weeks after discontinuing lenalidomide,90 days after discontinuing daratumumab and 6 months after discontinuing elranatamab.
• \. Men with partners of childbearing potential, even men with a successful vasectomy, that refuse to use a condom during intercourse, from initiating induction therapy to ≥4 weeks ys after discontinuing lenalidomide,. Furthermore, men must agree to not donate sperm during this period.
• \. Known positive for HIV or active hepatitis A, B or C: Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA
• Of note:
• Patients can be eligible if anti-HBc IgG positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative.
• o If anti-HBV therapy in relation to prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period.
• Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative, and all the other study criteria are still met.
• Active HCV infection: positive HCV RNA and negative anti-HCV.
• Of note:
• Patients with antiviral therapy for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion.
• Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible.
• \. Patient with an active systemic infection or severe infections requiring parenteral administration of antibiotics.
• \. Patients with a gastrointestinal disease/disorder that may significantly impact the absorption of oral treatments.
• \. Patients unable or unwilling to undergo antithrombic prophylaxis.
• \. A person under guardianship, trusteeship, or deprived of freedom by a judicial or administrative decision.