Phase Ib/II Trial Of Iberdomide-Combinations In Patients With Positive Minimal Residual Disease (>10-5) After Autologous Hematopoietic Cell Transplantation In The Upfront Management Of Patients With Multiple Myeloma
Similar to the paradigm established in other hematologic malignancies that are considered curable, the achievement of MRD(-) status is necessary for long term disease control in MM. The fact that the majority of patients remain MRD (+) after induction therapy and AHCT points to the opportunity to deploy novel agents with complementary mechanism of action and favorable toxicity profile to reach and maintain MRD (-) status. Given its favorable toxicity profile, the convenience of oral administration, and compelling single agent activity even in heavily pretreated MM, iberdomide is likely amenable to long term therapy in patients with high-risk of relapse/progression identified by the persistence of MRD(+). The investigators intend to develop combination(s) of iberdomide with other agents with complementary mechanism of action in the consolidation setting post AHCT in order to achieve and sustain MRD (-).
• Age \>18 years with no upper age limit
• Confirmation of newly diagnosed multiple myeloma (MM) with 1-2 prior regimens utilized in induction that included an immunomodulatory agent (IMiD) and a proteasome inhibitor (PI) combined or in different regimens
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Prior AHCT 100-180 days prior to initiation of protocol-directed therapy
• MRD ≥ 10\^-5 by clonoSEQ® NGS platform, determined 60-120 days after AHCT as part of the usual care.
• No prior disease progression (either before or since AHCT)
• Overall response (i.e post-AHCT compared to historical baseline prior to initiation of any therapy for MM) ≥ PR.
• Measurable disease at the time of the initial diagnosis (i.e. prior to starting any therapy for MM) meeting at least one of the following criteria:
‣ Serum monoclonal (M) protein ≥1.0 g/dl
∙ 200 mg of M protein/24h in the urine
⁃ Difference between involved and uninvolved free light chain ≥10 mg/dL and abnormal kappa to lambda ratio.
• Adequate hepatic function evidenced by AST and ALT ≤ 3 x ULN and bilirubin ≤ 1.5 ULN.
⁃ Adequate bone marrow function evidenced by platelets ≥ 75,000 /mm3 (without transfusion of platelets in the prior 7 days) and absolute neutrophil count ≥ 1,000/mm3.
⁃ Creatinine clearance (CrCl) ≥ 40 mL/minute within 28 days prior to start of therapy either measured or calculated using standard Cockcroft and Gault formula (available in https://www.kidney.org/professionals/KDOQI/gfr\_calculatorCoc ).
⁃ Females of childbearing potential (FCBP) must have two negative pregnancy tests as verified by the investigator and agree to ongoing pregnancy testing and to practice contraception during treatment. Male subjects must agree to practice contraception and refrain from donating sperm during treatment.
⁃ In line with the higher incidence of MM in Blacks, and to address the historical underrepresentation of ethnical minorities in MM trials, at least 25% of the enrolled patients will be of ethnical minorities.
⁃ Written informed consent in accordance with federal, local, and institutional guidelines.