High Dose Therapy Followed by Autologous Transplantation for Myeloma Patients With Severe Renal Impairment

Study Overview
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Brief Summary
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Multiple myeloma (MM) is a malignant plasma cell disorder, characterized by the presence of more than 10 % of clonal plasma cells in the bone marrow. Therapeutic intervention is recommended when at least one of the myeloma defining events occurs (CRAB features). Renal impairment (RI) is one of the most common complications of MM, accounting for 20-30 % of MM patients at diagnosis and 40-50% of patients during the course of their disease. To date, there is no defined consensus for the management of myeloma patients with renal failure. It is then of clinical importance to better considering available therapeutic options to improve responses and survival of these patients.

Detailed Description
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RI is associated with poor prognosis and short median survival (32 months vs 55 months for MM patients with normal renal function). Thus, RI remains a major challenge for hematologists, including decisions on optimal anti-myeloma therapy, potential dialysis, supportive care and quality of life. The combination of a proteasome inhibitor and an immunomodulator is the preferred induction treatment for newly diagnosed transplant-eligible MM patients. After induction, high-dose therapy with Autologous Stem Cell Transplant (ASCT) is the standard of care for these patients. However, concerns related to management of comorbidities and treatment side effects question about therapeutic options for patients with severe renal damage. Of interest, recent studies argued that high-dose therapy followed by ASCT could be a feasible and safe method for renal failure MM patients. Yet, these observations on small sample size patients groups need to be confirmed with standardized conditions. This study proposes to evaluate the efficacy and the safety of this therapeutic strategy in MM patients with severe renal impairment.

Official Title
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A Prospective, Non-interventional, Multinational Study Evaluating the Efficacy and the Safety of High Dose Therapy Followed by Autologous Hematopoietic Stem Cell Transplantation as a Frontline Therapy for Myeloma Patients With Severe Renal Impairment (IRMYG Study)

Conditions
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Multiple Myeloma, Renal Failure

Intervention / Treatment
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* Other: Data collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≤ 66 years-old Patients with symptomatic, measurable and newly diagnosed multiple myeloma associated: Severe renal failure at the time of transplantation (creatinine clearance < 40 ml/min/1.73m², CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration) Partial response after induction treatment For patients who undergo autologous transplantation, absence of known contraindication for transplantation Absence of amylose Patient affiliated to a social security regimen or beneficiary of the same Signed written informed consent form Exclusion Criteria: Patient without at least a partial hematological response following the induction stage Medical history of previous malignancy Patient under guardianship or deprived of his liberty or any condition that may affect the patient's ability to understand and sign the informed consent (art. L.1121-6, L.112-7, L.1211-8, L.1211-9) Pregnant or breastfeeding woman Declining participation

Ages Eligible for Study
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Minimum Age: 66 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Myeloma patients with severe renal impairment<br>Myeloma patients with severe renal impairment. Data collection will concern myeloma patients with severe renal impairment who are susceptible to undergo autologous transplantation. | Other: Data collection<br>* Myeloma patients with severe renal impairment who are susceptible to undergo autologous transplantation will be followed in this study, and data related to the pathology, treatments and transplantation will be reported.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non Relapse Mortality post-transplantation | Non-relapse mortality at Day +100 post-transplantation will be reported. | 100 days post-transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival at 2 years post-transplantation will be reported. | 2 years post-transplantation | 
| progression-free survival | progression-free survival at 2 years post-transplantation will be reported. | 2 years post-transplantation | 
| Number of toxicities | Number of hematological and extra-hematological toxicities linked to autologous stem cell transplantation will be reported during 2 years. | 2 years post-transplantation | 
| presence of hematological response | The presence of hematological response at Day+100 and at 6 months post-transplantation will be reported. | 6 months | 
| Level of renal response | Level of renal response at 3 months, 6 months and one year post-transplantation will be quantified and reported. | 3 months, 6 months and one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Renal Failure, Autologous Hematopoietic Stem Cell Transplantation (ASCT), Melphalan