GCSF-Free Stem HSC Mobilization for MM Autologous Transplant: 85-Mgta-145 and Plerixafor Study

MGTA-145, a promising CXCR2 agonist, has demonstrated effective hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical models and healthy volunteers, indicating its potential the first GCSF-free regimen for HSC mobilization. We conducted a phase 2 trial (NCT04552743) of MGTA-145 + plerixafor to investigate further its efficacy in patients with multiple myeloma (MM). The primary endpoint was the collection of ≥2 x 10⁶ CD34+ cells/kg in up to 2 days of mobilization/apheresis. Secondary endpoints included a collection of 4 and 6 x 10⁶ CD34+ cells/kg, safety, and engraftment.

The trial enrolled 25 patients, with the primary cohort comprising 15 patients and an additional ten patients in the expansion cohort. Eligibility criteria included being between 18-70, within one year of starting treatment, and having a CrCl > 30 ml/min. Plerixafor was administered subcutaneously, followed by an intravenous injection of MGTA-145 (0.03 mg/kg) over 3-10 minutes, with apheresis taking place within 30 minutes. If the day one yield was <6 x 10⁶ CD34+ cells/kg, mobilization was repeated on day 2. In this study, 24 (96%) patients with hematologic cancers were given Plerixafor at a dose of 0.24 mg/kg. The median total yield of hematopoietic stem cells (HSCs) was 5.0 (1.1 to 16.2) CD34+ cells/kg x 10⁶, with day one and day two yields being 3.4 (0.3 to 16.2) and 1.9 (ranging from 0.5 to 4.6) CD34+ cells/kg x 10⁶, respectively.

The primary endpoint, which was collecting sufficient HSCs in less than two days of mobilization and apheresis to proceed to transplant, was met by 88% (22) of patients, with 68% (17) completing the endpoint in just one day (2 x 106 CD34+ cells/kg). For the secondary endpoints of collecting 4 and 6 x 10⁶ CD34+ cells/kg in less than two days, 68% (17) and 40% (10) of patients met the criteria, respectively. Overall, the MGTA-145+plerixafor regimen was well-tolerated, with 60% of patients (grade 1, n= 14, grade 2, n=1) experiencing at least one treatment-emergent adverse event (TEAE) related to MGTA-145. The most common TEAE was pain 44% (11), with 38% of patients (9) experiencing acute onset transient bone pain with MGTA-145 lasting between (duration: 7 minutes, range: 3-28). A total of 18 patients underwent transplant with MGTA-145 graft, combined with melphalan 200 mg/m² in 15 patients, and a median of 3.5 (2.2-8.1) x 10⁶ CD34+ cells/kg was infused. All patients achieved engraftment, with a median time of 12 days (11-15) for neutrophil engraftment and 17.5 days (15-33) for platelet engraftment. About 14 patients had day 100 follow-ups, and all had durable engraftment.

Among the 23 grafts evaluated with next-generation flow cytometry, 74% (17 of 23) were minimal residual disease negative. CD90+CD45RA- was highly enriched among the CD34+ cells, a subset of long-term engrafting HSCs, (median: 36% of CD34+ cells, range 10-66%, N=25).

This study revealed the assessment of the G-CSF-free regimen of MGTA-145 + plerixafor for HSC cell mobilization in hematologic cancers. The primary endpoint was met in 88% of patients, and the regimen was well-tolerated, resulting in timely and durable engraftment.

Source: https://tandem.confex.com/tandem/2022/meetingapp.cgi/Paper/19107

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04552743

Lowsky, R., Meyer, E. H., Rezvani, A. R., Weng, W. K., Frank, M. J., Shiraz, P., Girgenti, D., Goncalves, K. A., Schmelmer, V., Davis, J., Lu, Y., Shizuru, J. A., & Miklos, D. B. (n.d.). 85 – Mgta-145 + Plerixafor Provides GCSF-Free Rapid and Reliable Hematopoietic Stem Cell Mobilization for Autologous Stem Cell Transplant in Patients with Multiple Myeloma: A Phase 2 Study. https://tandem.confex.com/tandem/2022/meetingapp.cgi/Paper/19107