Phase II study of novel CXCR2 agonist and Plerixafor for rapid stem cell mobilization in patients with multiple myeloma

Blood Cancer J. 2024 Oct 9;14(1):173. doi: 10.1038/s41408-024-01152-1.

Abstract

MGTA-145 or GROβT, a CXCR2 agonist, has shown promising activity for hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical studies and healthy volunteers. Twenty-five patients with multiple myeloma enrolled in a phase 2 trial evaluating MGTA-145 and plerixafor for HSC mobilization (NCT04552743). Plerixafor was given subcutaneously followed 2 h later by MGTA-145 (0.03 mg/kg) intravenously with same day apheresis. Mobilization/apheresis could be repeated for a second day in patients who collected <6 ×106 CD34+ cells/kg. Lenalidomide and anti-CD38 antibody were part of induction therapy in 92% (n = 23) and 24% (n = 6) of patients, respectively. Median total HSC cell yield (CD34+ cells/kg × 106) was 5.0 (range: 1.1-16.2) and day 1 yield was 3.4 (range: 0.3-16.2). 88% (n = 22) of patients met the primary endpoint of collecting 2 ×106 CD34+ cells/kg in ≤ two days, 68% (n = 17) in one day. Secondary endpoints of collecting 4 and 6 × 106 CD34+ cells/kg in ≤ two days were met in 68% (n = 17) and 40% (n = 10) patients. Grade 1 or 2 adverse events (AE) were seen in 60% of patients, the most common AE being grade 1 pain, usually self-limited. All 19 patients who underwent transplant with MGTA-145 and plerixafor mobilized HSCs engrafted successfully, with durable engraftment at day 100. 74% (17 of 23) of grafts with this regimen were minimal residual disease negative by next generation flow cytometry. Graft composition for HSCs and immune cells were similar to a contemporaneous cohort mobilized with G-CSF and plerixafor.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Benzylamines* / therapeutic use
  • Cyclams* / pharmacology
  • Cyclams* / therapeutic use
  • Female
  • Hematopoietic Stem Cell Mobilization* / methods
  • Hematopoietic Stem Cell Transplantation
  • Heterocyclic Compounds* / administration & dosage
  • Heterocyclic Compounds* / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / therapy
  • Receptors, Interleukin-8B* / agonists

Substances

  • plerixafor
  • Cyclams
  • Benzylamines
  • Heterocyclic Compounds
  • Receptors, Interleukin-8B
  • CXCR2 protein, human

Associated data

  • ClinicalTrials.gov/NCT04552743