This phase II trial compares standard consolidation with daratumumab, carfilzomib, lenalidomide, and dexamethasone to consolidation with teclistamab following standard induction therapy and autologous hematopoietic stem cell transplant for improving overall survival of patients with plasma cell leukemia. Consolidation therapy is treatment given after initial therapy to kill any cancer cells that may remain in the body. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Carfilzomib inhibits protein complexes called proteasomes, which inhibits cancer cell growth and leads to cancer cell death. Lenalidomide may help kill cancer cells and prevents the growth of blood vessels that cancer cells need to survive. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Teclistamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving teclistamab as consolidation therapy after induction and autologous hematopoietic stem cell transplant may improve survival outcomes in patients with plasma cell leukemia, compared to standard consolidation with daratumumab, carfilzomib, lenalidomide, and dexamethasone.
Documented diagnosis of primary plasma cell leukemia according to IMWG criteria defined as 5% or greater circulating plasma cells at the time of initial diagnosis
Serum monoclonal protein ≥ 0.5 g/dL or
Urine monoclonal protein ≥ 200 mg/24 hours (h) or
Serum free light chain (FLC) assay: Serum free light chain ≥ 100 mg/L and abnormal serum free light chain ratio
None
Parallel
Autologous Hematopoietic Stem Cell Transplantation
Procedure/SurgeryUndergo autoHSCT
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Carfilzomib
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo PET/CT and/or CT
Daratumumab and Recombinant Human Hyaluronidase
DrugGiven SC
Dexamethasone
DrugGiven PO
Fludeoxyglucose F-18
Other interventionUndergo FDG PET/CT
Lenalidomide
DrugGiven PO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Melphalan
DrugGiven IV
Plerixafor
DrugGiven SC
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Recombinant Granulocyte Colony-Stimulating Factor
Biological/VaccineGiven SC
Stem Cell Isolation
Procedure/SurgeryUndergo stem cell collection
Teclistamab
DrugGiven SC
Transthoracic Echocardiography Test
Procedure/SurgeryUndergo TTE
Overall survival (OS)
The time to event outcome of overall survival will be evaluated and compared using a log-rank test to compare differences between arms. OS distributions will be evaluated graphically using the methods of Kaplan and Meier, along with estimation of the 3-year OS rates with corresponding 95% confidence intervals and other time points of interest. In a secondary manner, Cox regression models will also be used to evaluate differences in OS between treatment arms when adjusting for factors of interest as well as stratifying on the stratification factors including prior treatment status and t(11;14) status.
Incidence of adverse events
Adverse events (AEs) will be summarized per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5, and where toxicities will be defined as adverse events that are deemed to be at least possibly treatment-related (i.e., attribution of "possibly", "probably", or "definite"). Note that some AEs will be defined using other criteria where specified. The maximum grade for each type of treatment-related AE will be recorded for each patient, and the frequency of each will be summarized across all patients for the induction phase, and by treatment arm for the consolidation and maintenance phases of treatment. Frequency tables and graphical evaluations of AEs and treatment-related AEs will be summarized and evaluated to assess if there are any patterns or differences in the rates or types of AEs including, but not limited to, AEs of special interest including cytokine release syndrome, neurotoxicity, and second primary malignancies.
Progression free survival (PFS)
Will use Kaplan-Meier analyses and Cox regression models to evaluate this endpoint and how the PFS distributions differ between the treatment arms.
Overall response rate
Overall response rate will be summarized for each of the treatment arms and defined as the number of patients who achieve at least a partial response to therapy divided by the total number of patients treated on that arm. Will summarize the incidence and depth of objective response both post-induction as well as post-consolidation. Response rates will be calculated along with 95% binomial confidence intervals for each of the t(11;14) subjects and treatment arms.
Minimal residual disease (MRD) negativity
MRD negativity will be evaluated over the course of the trial when a bone marrow biopsy and aspirate is obtained to confirm complete response or better and will be summarized based on treatment arm and t(11;14) status. Repeated measures models will also be used to evaluate changes over time along with graphical analyses to assess patterns or differences based on subgroup and/or treatment and how these relate to key therapeutic milestones. Time-dependent covariate analyses will also be used to explore the relationship of this outcome and how these longitudinal outcomes may correspond to PFS and OS in these patients.
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