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

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.

Fig. 1

Stem cell yield per patient with MGTA-145 and plerixafor mobilization and same day apheresis.

Fig. 2. Characteristics of apheresis products after mobilization with MGTA-145 and plerixafor compared with standard of care mobilization (G-CSF and/or on demand plerixafor).

A HSCs (CD34 + CD90+ and CD34 + CD90 + CD45RA-) shown as % of CD34+ cells assessed by FACS. B T, B and NK cells shown as % of the lymphocytes assessed by FACS. C Frequency of total, memory and naïve CD4 + T cells as assessed by FACS. D Frequency of total, memory and naive CD8 + T cells as assessed by flow cytometry. Each figure shows individual datapoints as circles or squares and the bar represents the median.

Fig. 3. Immune reconstitution of T cell subsets and NK cells in peripheral blood following autologous stem cell transplant with MGTA-145 and plerixafor mobilized hematopoietic stem cells.

The graph represents absolute cell counts/μl shown as median and interquartile range of (A). T cells (CD3 + ), (B) NK cells (CD3-CD56 + ), C CD4 T cells (CD3 + CD4 + ), (D) CD8 T cells (CD3 + CD8 + ), (E) CD4 naive T cells (CD45RA + ), (F) CD8 naive T cells (CD45RA + ), (G) CD4 memory T cells (CD45RO + ), and (H) CD8 memory T cells (CD45RO + ) as assessed by flow cytometry at baseline and at day 28 and 100 after autologous stem cell transplantation with MGTA-145 and plerixafor mobilized HSCs. P values at each timepoint represent comparison vs. baseline.