Motixafortide Prior to HCT Shows Benefit in Multiple Myeloma

At the American Society of Hematology (ASH) annual meeting, researchers presented results of a post-hoc analysis of the phase III GENESIS trial.

In this video, courtesy of the Video Journal of Hematological Oncology (VJHemOnc), John DiPersio, MD, PhD, of Washington University School of Medicine in St. Louis, discusses the analysis, which investigated motixafortide, a CXCR4 antagonist, as a mobilizing agent prior to autologous hematopoietic cell transplantation in patients with multiple myeloma.

Following is a transcript of his remarks:

So, the GENESIS trial is a trial designed to study a new drug, and its easier name to pronounce is BL-8040, which is motixafortide. And this is a CXCR4 inhibitor that is slightly different than plerixafor [Mozobil].

First of all, it’s slightly more active in preclinical models. Number two, it blocks for a much longer period of time. For instance, plerixafor blocks very transiently and is washed off the receptors, so it has a very high off rate, while BL-8040, motixafortide, has a very long occupancy rate and a very slow off rate, so it actually continues to mobilize. And so you only need one dose every 2 days. So, that’s a big benefit. So more active, longer acting.

And the goal was to combine this CXCR4 inhibitor like we did with our previous studies with plerixafor that was approved by the FDA in 2008, 2010, I can’t even remember [Note: it first approved on Dec. 15, 2008]. But the same concept. We combined it with G-CSF [granulocyte colony-stimulating factor] and randomized myeloma patients to receive either G-CSF alone as a mobilizing agent or G-CSF plus motixafortide (BL-8040). And the differences between the two groups were dramatic.

This was a prospective, double-blind, randomized trial, so it has all the trappings of a well-designed clinical trial. It was a 2:1 randomization to the combination of BL-8040 and G-CSF versus the control group. And at 1 day of apheresis, approximately 90% of the patients reached the target of 6 × 10⁶ CD34+ cells/kg versus only 9% in the control group. So, a dramatic difference. And by 2 days, the difference was 92% to about 16%. So, there was a huge difference between the two groups and that’s highly statistically significant.

The drug was also very well tolerated, with only slight injection-site reactions. So, now we have for the first time a second alternative CXCR4 inhibitor that actually on paper looks more active and has a lower off rate and a higher binding affinity to CXCR4. And when combined with G-CSF dramatically synergizes the mobilization of stem cells in myeloma patients. This trial is a registration trial, which will be used for FDA approval in the next few months.