What Mobilizing Agents Are and What They Mean for Your Stem Cell Collection

For many patients with hematological malignancies, autologous hematopoietic stem cell transplantation (ASCT) remains a critical part of treatment. This process involves collecting CD34+ hematopoietic stem and progenitor cells (HSPCs) from the bloodstream which are later reinfused with high dose-chemotherapy. 

However, for many patients, it is not always easy to mobilize enough stem cells for transplantation. 

Is It Normal to Not Collect Enough Stem Cells?

If you are a patient who has experienced this first-hand or know one who has, do not be discouraged; mobilization under standard approaches remains a significant challenge, with 40-50% of patients struggling to collect an optimal number of CD34+ cells for their transplant. 

Advancements have revealed that mobilization strategies, such as introducing motixafortide (a novel mobilizing agent), have significantly increased the number of stem cells collected. 

Current Methods Are Not Enough

For decades, agents such as G-CSF have been used to simulate the production and release of CD34+ stem cells into the bloodstream. G-CSF and other similar agents work by stimulating the bone marrow to increase blood cell production, which in turn pushes more stem cells into circulation. 

Despite the widespread use of G-CSF alone, it may not be enough to mobilize sufficient CD34+ cells for transplantation. As shared above, 40-50% of people will require additional mobilizing agents, with multiple injections over several days. Side effects of these injections may include bone pain and fatigue.

Improving the Process: Mobilization Agents at Work

Circumventing these limitations of G-CSF alone has been addressed through the addition of mobilization agents like plerixafor (Mozobil, Genzyme) or motixafortide (Aphexda, BioLineRx). These work to weaken the grip that keeps stem cells anchored in the bone marrow. Without this anchor, stem cells are freed from their bone marrow niches and start moving into the bloodstream.

Motixafortide Shows Promise 

Motixafortide has shown promise in bypassing stem cell collection limitations, as demonstrated in the Phase 3 GENESIS trial (NCT03246529). In this study, 92.5% of patients who received motixafortide plus G-CSF achieved the primary endpoint of collecting 6 × 106 CD34+ cells/kg or more in up to two apheresis sessions, compared to 26.2% of patients in the G-CSF alone arm. 

88.3% of patients in the motixaforitde group were able to achieve the target yield in a single session compared to 9.5% in the control group. 

Importantly, time to engraftment remained similar between the two arms, indicating that the robust mobilization did not compromise safety or prolong recovery.

Patients typically undergo stem cell collection after receiving a quadruplet induction therapy, which includes an immunomodulator, proteasome inhibitor, steroid, and an anti-CD38 monoclonal antibody, before an autologous stem cell transplant (ACST).

Traditionally, stem cell collection beyond 4-6 cycles of the induction therapy has been avoided due to concerns that extended exposure to Revlimid (lenalidomide) and anti-CD38 antibodies could hinder mobilization. 

However, Motixafortide’s effectiveness in mobilization may change this approach, allowing for later collection without the same risks. This could also enable better identification of high-risk patients without requiring repeated bone marrow samples, improving patient care by reducing discomfort while providing more precise treatment insights.

Motixafortide is being studied for its potential in other hematologic malignancies and gene-editing therapies where higher numbers of stem cells are required. 

Future research in this field will likely focus on healthcare resource utilization: evaluating whether Motixafortide and other similar mobilizing agents may minimize the need for repeated mobilization attempts and prolonged hospital stays.

Potential Side Effects Investigated 

A study conducted at Fox Chase Cancer Center investigated a modified premedication protocol to reduce adverse events (AEs) associated with motixafortide. The retrospective analysis, presented at the 66th ASH Annual Meeting, included 24 multiple myeloma patients receiving motixafortide for stem cell mobilization.

This research showed that when an 8 mg IV dexamethasone dose was added to a premedication protocol for motixafortide, along with other standardized medicines, it reduced hypersensitivity and injection site sensitivity while still allowing for optimal stem cell collection.

Final Thoughts

For multiple myeloma patients, efficient stem cell mobilization is essential for a successful stem cell transplant. While G-CSF and plerixafor have been widely researched and used, they have limitations, particularly in patients undergoing extended therapy. 

Motixafortide represents a significant advancement in myeloma and hematological malignancy care. With the ability to mobilize primitive stem cells efficiently, it may redefine collection practice, improving access to transplantation. For patients and care teams, this innovation marks a step toward a more predictable, efficient, and patient-friendly mobilization process.

Sources: 

• Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial
• Final analysis of a phase II trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma without transplant
• Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma
• Paper: Comparative Analysis of Dexamethasone-Enhanced Pre-Medication in Motixafortide-Induced Hematopoietic Stem Cell Mobilization for Multiple Myeloma: A Retrospective Study