This phase II trial tests how well giving infliximab works for the prevention of cytokine release syndrome (CRS) during treatment with teclistamab or talquetamab in patients with multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). CRS and neurologic toxicity (damage to the nervous system which includes the brain, spinal cord, and nerves) are potential risks of treatment with talquetamab and teclistamab. CRS involves a release of a large amount of proteins into the bloodstream causing inflammation. This may cause changes in blood pressure and heartbeat, flu-like symptoms (nausea, fever, and chills), and/or affect the lung/liver/kidney function. It may also cause certain brain-related symptoms, such as dizziness, weakness, confusion, difficulty speaking, and/or decreased brain function (possible paralysis and/or coma). Infliximab is a drug that prevents the tumor necrosis factor-alpha (TNF-α) from working. TNF-α is a cytokine, or chemical messenger, that helps your immune system produce inflammation. Giving infliximab may work well for the prevention of cytokine release syndrome during treatment with teclistamab or talquetamab in patients with relapsed or refractory multiple myeloma.
PRIMARY OBJECTIVE: I. To determine the efficacy of infliximab as CRS prophylaxis for patients with relapsed/refractory multiple myeloma (RRMM) treated with teclistamab or talquetamab therapy. SECONDARY OBJECTIVES: I. To estimate the incidence of grade ≥ 3 CRS within cycle 1 (28 days). II. To estimate the incidence of all-grade and grade ≥ 3 neurologic toxicity (including Immune effector cell-associated neurotoxicity syndrome \[ICANS\]) within cycle 1 (28 days). III. To estimate the incidence of grade ≥ 3 infection within cycle 1 (28 days). IV. To estimate the incidence of grade ≥ 3 anemia within cycle 1 (28 days). V. To estimate the incidence of grade ≥3 neutropenia within cycle 1 (28 days). VI. To estimate the incidence of grade ≥ 3 thrombocytopenia within cycle 1 (28 days). VII. To determine the overall response rate (ORR) (per International Myeloma Working Group \[IMWG\] criteria). EXPLORATORY OBJECTIVE: I. Provide a descriptive summary of changes in plasma cytokine concentrations in patients treated with teclistamab or talquetamab with prophylactic infliximab. OUTLINE: Patients receive infliximab intravenously (IV) on day 1, two to four hours prior to treatment with standard of care teclistamab or talquetamab. Patients then receive teclistamab subcutaneously (SC) or talquetamab SC on days 1, 3, 5, 15, 22, and 28 per treating physician discretion. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and may undergo an x-ray or positron emission tomography (PET)-computed tomography (CT) scan during screening and also blood sample collection throughout the study. After completion of study treatment, patients are followed up at day 28.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
35
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo PET-CT
Given IV
Undergo PET-CT
Given SC
Given SC
Undergo x-ray
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
RECRUITINGIncidence of all-grade cytokine release syndrome (CRS)
Will be described per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. Will be reported as a proportion together with 95% confidence intervals.
Time frame: From baseline, up to day 28
Rates of grade ≥ 3 CRS
Will be described per ASTCT guidelines. Will be reported as a proportion together with 95% confidence intervals.
Time frame: From baseline up to day 28
Rates of all-grade neurologic toxicity
Adverse events (AE) will be summarized using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and will be described using frequency tables and will be reviewed for toxicity patterns. Immune effector cell-associated neurotoxicity syndrome (ICANS) will be described per ASTCT guidelines. The incidence of neurologic toxicity, including ICANS (all-grade and grade ≥ 3), will be calculated with 95% confidence intervals.
Time frame: From baseline, up to day 28
Rates of grade ≥ 3 neurologic toxicity
AE will be summarized using the NCI CTCAE v 5.0 and will be described using frequency tables and will be reviewed for toxicity patterns. ICANS will be described per ASTCT guidelines. The incidence of neurologic toxicity, including ICANS (all-grade and grade ≥ 3), will be calculated with 95% confidence intervals.
Time frame: From baseline, up to day 28
Incidence of grade ≥ 3 infection
AE will be summarized using the NCI CTCAE v 5.0 and will be described using frequency tables and will be reviewed for toxicity patterns.
Time frame: From baseline, up to day 28
Incidence of grade ≥ 3 anemia, neutropenia, and/or thrombocytopenia
AE will be summarized using the NCI CTCAE v 5.0 and will be described using frequency tables and will be reviewed for toxicity patterns.
Time frame: From baseline, up to day 28
Overall response rate (ORR)
Defined as the proportion of subjects whose best response is partial response or better and will be reported with 95% binomial exact confidence intervals. ORR among patient subgroups (patients receiving teclistamab versus talquetamab) will be compared using the Fisher exact test.
Time frame: From baseline, up to day 28
The Ohio State University Comprehensive Cancer Center
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