Multiple myeloma, the second most-common blood cancer, is a cancer in which malignment plasma cells build up in the bone marrow, crowding out healthy blood cells and preventing the production of properly functioning antibodies.

Autologous stem cell transplantation (ASCT) is the preferred first-line treatment for multiple myeloma,1 and integral to the prospect of improving survival and helping to restore the immune system.

Prior to ASCT, patients undergo apheresis, a procedure to collect stem cells for the transplant. Stem cells need to be mobilized, or moved, from the bone marrow to the bloodstream for collection during apheresis.

ASCT success depends on adequate mobilization and collection of stem cells.2 While more multiple myeloma patients are candidates for ASCT than ever before,3 stem cell mobilization and collection is a growing challenge.

  • Increasing age makes it increasingly difficult to collect enough stem cells for ASCT4
    • The proportion of older patients receiving ASCT has increased over the last decade, with 38% of patients aged >65 years in 20215*
  • Standard 3- and 4-drug induction therapy can further impair mobilization, with fewer cells mobilized and additional days of apheresis required6,7
*This includes MM/plasma cell disorders, non-Hodgkin lymphoma, and Hodgkin lymphoma.8
Factors to consider:

Up to 47% of patients

have had challenges collecting target numbers of stem cells within one apheresis session, depending on induction regimens and mobilization strategies8,9

Multiple apheresis sessions can lead to:

  • More adverse events
  • Higher costs
  • Inconvenience for patients and transplant center administrators10

As age and use of induction therapy regimens increase, the majority of patients will require CXCR4 antagonist mobilization either upfront or as rescue for ASCT7,11

Motixafortide in Multiple Myeloma

In September 2023, the U.S. Food and Drug Administration (FDA) approved motixafortide – a CXCR4 antagonist with long receptor occupancy12 – in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

The FDA approval of motixafortide was based on results from the 2-part, Phase 3 GENESIS trial, a randomized, double-blind, placebo-controlled study. Data from the GENESIS trial was published in the peer-reviewed journal Nature Medicine and included patients representative of current multiple myeloma populations undergoing hemopoietic stem cell transplant (HSCT), including older patients and those who received lenalidomide-containing induction therapies – factors associated with impaired HSTC mobilization.

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How Motixafortide Works

Motixafortide, a CXCR4 antagonist with long receptor occupancy (greater than 72 hours), is a 14-amino-acid synthetic cyclic peptide. It blocks CXCR4 on hematopoietic stem cells (HSC) from binding to its ligand, CXCL12, that retains HSC in the bone marrow and lymph nodes. This blocking releases the HSC to the peripheral blood, where they are available for collection during apheresis.

Stem Cell Mobilization
Scientific illustration depicting how motixafortide works in stem cell mobilization
Scientific illustration depicting how motixafortide works in stem cell mobilization

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References: 1. Dhakal B, Shah N, Kansagra A, et al. ASTCT clinical practice recommendations for transplantation and cellular therapies in multiple myeloma. Transplant Cell Ther. 2022;28(6):284-293. 2. Giralt S, Costa L, Schriber J, et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biol Blood Marrow Transplant. 2014;20(3):295-308. 3. Swan D, Hayden PJ, Eikema DJ, et al. Trends in autologous stem cell transplantation for newly diagnosed multiple myeloma: changing demographics and outcomes in European Society for Blood and Marrow Transplantation centres from 1995 to 2019. Br J Haematol. 2022;197(1):82-96. 4. Morris CL, Siegel E, Barlogie B, et al. Mobilization of CD34+ cells in elderly patients (>/= 70 years) with multiple myeloma: influence of age, prior therapy, platelet count and mobilization regimen. Br J Haematol. 2003;120(3):413-423. 5. Bolon YT, Atshan R, Allbee-Johnson M, Estrada-Merly N, Lee SJ. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR summary slides, 2022. Accessed August 8, 2023. https://cibmtr.org/Files/Summary-Slides--Reports/The-US-Summary-Slides-2022-v3---web-version.pptx. 6. Hulin C, Offner F, Moreau P, et al. Stem cell yield and transplantation in transplant-eligible newly diagnosed multiple myeloma patients receiving daratumumab + bortezomib/thalidomide/dexamethasone in the phase 3 CASSIOPEIA study. Haematologica. 2021;106(8):2257-2260. 7. Chhabra S, Callander N, Watts NL, et al. Stem cell mobilization yields with daratumumab- and lenalidomide-containing quadruplet induction therapy in newly diagnosed multiple myeloma: findings from the MASTER and GRIFFIN trials. Transplant Cell Ther. 2023;29(3):174.e1-174.e10. 8. DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009;113(23):5720-5726. 9. Edmisson J, et al. Poster presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. 10. Shaughnessy P, Chao N, Shapiro J, et al. Pharmacoeconomics of hematopoietic stem cell mobilization: an overview of current evidence and gaps in the literature. Biol Blood Marrow Transplant. 2013;19(9):1301-1309. 11. Giralt S, Costa L, Schriber J, et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biol Blood Marrow Transplant. 2014;20(3):295-308. 12. APHEXDA. Prescribing information. BioLineRx Ltd; 2023.

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