Multiple myeloma is a type of blood cancer that can come back even after effective treatment. After high-dose therapy and autologous stem cell transplantation (ASCT), some patients have no visible signs of disease, but small numbers of cancer cells may still remain in the body. This is called measurable residual disease (MRD). These remaining cells may lead to disease relapse. The purpose of this study is to find out whether a new maintenance treatment can eliminate these remaining cancer cells more effectively than the current standard treatment. More effective maintenance therapy may help reduce the risk of disease progression and improve long-term outcomes for patients. This study, called TiTan, is a phase III, multicenter clinical trial conducted in Poland. It will include 248 adult patients with newly diagnosed multiple myeloma who have undergone ASCT, have no signs of disease progression, but still have detectable MRD. Participants will be randomly assigned (by chance) to one of two treatment groups. Neither the patient nor the doctor can choose the group. In the experimental group, patients will receive two immunotherapy medicines, teclistamab and talquetamab. If MRD becomes undetectable after the protocol-defined period, treatment may be stopped and the patient will continue under observation. In the standard treatment group, patients will receive daratumumab and lenalidomide, which are commonly used maintenance treatments. The duration and adjustments of treatment may depend on MRD results. The main goal of the study is to determine how many patients achieve undetectable MRD after 12 months of treatment together with a complete response to therapy. This will show whether the new treatment is more effective in removing residual cancer cells. The study will also evaluate how long patients live without disease progression, overall survival, treatment safety, and the impact of treatment on patients' daily functioning and quality of life. In addition, researchers will assess whether achieving undetectable MRD leads to better long-term outcomes. Patient safety will be closely monitored throughout the study. Participants will undergo regular medical check-ups, including blood tests, bone marrow tests, and imaging studies. All side effects will be carefully recorded and assessed according to international standards. Patients may withdraw from the study at any time without giving a reason. This non-commercial study aims to improve knowledge about maintenance treatment in multiple myeloma after ASCT and may help support future treatment decisions for patients with this disease.
Multiple myeloma is a malignant plasma cell disorder characterized by repeated relapses despite advances in treatment. Following induction therapy and high-dose chemotherapy with autologous stem cell transplantation (ASCT), many patients achieve deep clinical responses. However, a proportion of patients remain positive for measurable residual disease (MRD), indicating the presence of residual malignant plasma cells and an increased risk of disease progression. The TiTan study (protocol PMC011) is a phase III, randomized, open-label, multicenter clinical trial conducted in Poland. The study evaluates the efficacy and safety of two maintenance treatment strategies in adult patients with newly diagnosed multiple myeloma who remain MRD-positive after ASCT. The study is designed to evaluate whether maintenance therapy with teclistamab in combination with talquetamab can improve treatment outcomes compared with standard maintenance therapy with daratumumab and lenalidomide in participants with newly diagnosed multiple myeloma who remain MRD-positive after ASCT. This is a randomized, open-label, parallel-group study enrolling approximately 248 adult participants. Eligible participants have newly diagnosed multiple myeloma, have completed high-dose chemotherapy and ASCT, and have confirmed MRD positivity assessed using sensitive laboratory methods. Participants may receive up to two cycles of consolidation therapy after ASCT. Eligible participants are randomized within a defined period after transplantation to one of two treatment arms in a 1:1 ratio. Participants assigned to the experimental arm receive maintenance therapy with teclistamab and talquetamab. Participants assigned to the control arm receive maintenance therapy with daratumumab and lenalidomide. Treatment administration and duration follow protocol-defined procedures. Treatment response is assessed according to International Myeloma Working Group (IMWG) criteria. MRD is evaluated in bone marrow samples using next-generation flow cytometry (NGF) at a sensitivity level of 10-⁵. Disease assessments include evaluation of monoclonal protein using standard laboratory methods, including serum and urine protein electrophoresis, immunofixation, serum free light chain assessment, and imaging studies when clinically indicated. Participants are followed throughout the study for evaluation of disease status, response to treatment, safety, and survival outcomes. Following completion of study treatment, participants continue protocol-defined follow-up assessments. After disease progression, information on subsequent anti-myeloma therapies and long-term outcomes is collected until study completion. Safety and tolerability are assessed throughout the study using adverse event reporting, clinical examinations, and laboratory evaluations. Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Persistence of MRD after ASCT is associated with an increased risk of disease progression in multiple myeloma. This study evaluates whether an immunotherapy-based maintenance strategy can achieve deeper disease control than standard maintenance treatment in patients with residual disease after transplantation and further explores the relationship between MRD status and clinical outcomes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
248
Teclistamab is administered as part of combination immunotherapy according to protocol-defined dosing and schedule in participants receiving maintenance treatment for multiple myeloma.
Talquetamab is administered in combination with teclistamab as part of maintenance immunotherapy according to protocol-defined dosing and schedule.
Daratumumab is administered as part of standard maintenance therapy according to protocol-defined dosing and schedule in participants with multiple myeloma.
Lenalidomide is administered as continuous maintenance therapy according to protocol-defined dosing and schedule in combination with daratumumab.
Proportion of Participants Achieving MRD Negativity With Complete Response
The proportion of participants achieving measurable residual disease negativity at a sensitivity level of 10\^-5 together with complete response, assessed according to International Myeloma Working Group (IMWG) criteria at the specified timepoint.
Time frame: At Month 12
Progression-Free Survival
Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first.
Time frame: Through study completion, up to approximately 36 months after enrollment of the last participant
Change From Baseline in Global Health Status and Functional Scales Assessed by EORTC QLQ-C30
Mean change from baseline in global health status and functional scales assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).
Time frame: From baseline through study completion (up to approximately 36 months after enrollment of the last participant)
Change From Baseline in Multiple Myeloma-Specific Quality of Life Assessed by EORTC QLQ-MY20
Mean change from baseline in multiple myeloma-specific quality of life assessed using the European Organisation for Research and Treatment of Cancer Multiple Myeloma Module (EORTC QLQ-MY20).
Time frame: From baseline through study completion (up to approximately 36 months after enrollment of the last participant)
Overall Survival
Time from randomization to death from any cause.
Time frame: Through study completion, up to approximately 36 months after enrollment of the last participant
Proportion of Participants Achieving Complete Response or Better
The proportion of participants achieving complete response or better, assessed according to International Myeloma Working Group (IMWG) criteria.
Time frame: Through study completion, up to approximately 36 months after enrollment of the last participant
Progression-Free Survival in Subsequent Therapy (PFS2)
Time from randomization to progression following the next line of therapy or death from any cause.
Time frame: Through study completion, up to approximately 36 months after enrollment of the last participant
Proportion of Participants Achieving MRD Negativity
The proportion of participants achieving measurable residual disease negativity at a sensitivity level of 10\^-5.
Time frame: Through study completion, up to approximately 36 months after enrollment of the last participant
Duration of MRD Negativity
Time from first documented measurable residual disease negativity to loss of MRD negativity or disease progression.
Time frame: Through study completion, up to approximately 36 months after enrollment of the last participant
Incidence of Adverse Events
Number of participants experiencing adverse events, including severity and relationship to study treatment, assessed according to CTCAE criteria.
Time frame: From first dose up to study completion (approximately 36 months after enrollment of the last participant)
Incidence of Serious Adverse Events
Number of participants experiencing serious adverse events.
Time frame: From first dose up to study completion (approximately 36 months after enrollment of the last participant)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.