Assessment of Allogeneic Hematopoietic Cell Transplantation in Medicare Beneficiaries With Multiple Myeloma

Assessment of Allogeneic Hematopoietic Cell Transplantation in Medicare Beneficiaries With Multiple Myeloma: A Study to Develop Evidence of Effectiveness for the Centers for Medicare and Medicaid Services (CMS)

Multiple myeloma (MM) is the second most common hematologic malignancy in adults. The current standard of care for MM patients fit to undergo high dose conditioning chemotherapy is an autologous HCT (autoHCT). Allogeneic HCT (alloHCT) is the only potentially curative therapy available to patients with MM. However, the significant morbidity and mortality of this procedure historically limited its application in older patients.

Thus, although potentially curative, standard risk MM patients have excellent prognoses in the era of novel therapies which reduces the overall benefit of alloHCT. However, because the outcomes for high-risk MM remain poor despite the best available standard therapies (overall survival of 24-36 months), initial data suggest that alloHCT should be explored in this subset.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Other: Allogeneic Hematopoietic Stem Cell Transplant

Detailed Description

Multiple myeloma (MM) is the second most common hematologic malignancy in adults. Overall survival (OS) in MM has improved significantly in the last 15 years with the emergence of novel therapies such as thalidomide, bortezomib and lenalidomide. The median life expectancy of patients with MM treated in the current era is more than 6 years, while SEER data from a slightly earlier time period (2008-12) estimated the 5 year survival at 48.5%. However, prognosis is not uniform and varies considerably based on a presenting features and response to therapy.

The current standard of care for MM patients fit to undergo high dose conditioning chemotherapy is an autologous HCT (autoHCT). There is controversy regarding the timing of autoHCT after initial novel therapy induction with randomized trials showing similar OS whether done early or delayed to time of relapse as salvage therapy. However, more recent trials comparing early versus delayed transplant support the benefit of early upfront autoHCT.

Allogeneic HCT (alloHCT) is the only potentially curative therapy available to patients with MM. However, the significant morbidity and mortality of this procedure historically limited its application in older patients. Current data from the Center for International Blood and Marrow Research (CIBMTR) show transplant-related mortality rates of 23 (20-26)% at 5 years with myeloablative conditioning.

Thus, although potentially curative, standard risk MM patients have excellent prognoses in the era of novel therapies which reduces the overall benefit of alloHCT. However, because the outcomes for high-risk MM remain poor despite the best available standard therapies (overall survival of 24-36 months), initial data suggest that alloHCT should be explored in this subset.

• Study Type: Observational
• Enrollment (Estimated): 544

Contacts and Locations

• Study Contact: Name: Mona Patel; Phone Number: 414-805-0655; Email: mopatel@mcw.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55401
      • Recruiting
      • Center for International Blood and Marrow Transplant Research
      • Contact: Michael Tierney; Email: DatabaseIRB@NMDP.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

A prospective cohort study of approximately 544 patients receiving allogeneic HCT for multiple myeloma in CIBMTR centers in the US matched to a historical control patients treated with autoHCT between 2010 and 2016

Description

Inclusion Criteria:

• Medicare beneficiary
• Stage II or III multiple myeloma and/or primary plasma cell leukemia
• Eligible to receive an allogeneic HCT from any suitable allogeneic donor (as determined by the transplant center) including umbilical cord blood
• Will receive allogeneic HCT at a US transplant center
• Agree to submit comprehensive clinical data on their pre- and post-transplant clinical status and outcomes to the CIBMTR

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Allogeneic HCT; Prospectively enrolled cohort of patients receiving allogeneic hematopoietic cell transplantation for multiple myeloma	Other: Allogeneic Hematopoietic Stem Cell Transplant; This observational study will compare outcomes of prospectively enrolled HCT recipients with outcomes of a cohort of matched autoHCT controls.
Historical autoHCT; Historical cohort of patients with autologous hematopoietic cell transplantation between 2010 and 2016

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare five-year survival	Compare five-year overall survival between the alloHCT cohort and an age and disease risk matched cohort of autoHCT patients	5 years post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	five-year PFS probabilities between the AlloHCT cohort and an age and disease risk matched cohort of autoHCT patients	5 years post transplant
Relapse or progression	Myeloma recurrence or progression will be defined per International Myeloma Working Group (IMWG) guidelines	5 years post transplant
Transplant related mortality	Death from any cause within 28 days after alloHCT or death in the absence of progression/relapse of MM after day 28 post transplant	5 years post transplant
Incidence of acute GVHD	Occurrence of Grade I, II and III/IV skin, gastrointestinal, or liver abnormalities fulfilling the Consensus criteria of Grades II-IV acute GVHD	5 years post transplant
Incidence of chronic GVHD	Occurrence of symptoms in any organ system fulfilling the criteria of chronic GVHD	5 years post transplant

Collaborators and Investigators

• Sponsor: Center for International Blood and Marrow Transplant Research
• Collaborators: National Marrow Donor Program
• Investigators: Study Chair: Anita D'Souza, MD, MS, CIBMTR, Medical College of Wisconsin; Study Chair: Parameswaran Hari, MD, MS, CIBMTR, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2017
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 18, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (Actual): April 25, 2017

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 17-CMS-MM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No