Plerixafor as a mobilization agent prior to ASCT in MM

An autologous stem cell transplant (ASCT) is the recommended first-line treatment for patients (pts) with multiple myeloma (MM) who are 65 years or younger, and fit. Prior to an ASCT, stem cells (SCs) are harvested from the pts’ blood in a procedure known as apheresis. For the apheresis to be successful, SCs need to be stimulated to move from the bone marrow to the bloodstream - a process called mobilization. The most common mobilization agents include granulocyte-colony stimulating factor (G-CSF), either alone or in combination with the chemotherapy drug cyclophosphamide (CY). To reduce toxic effects, there is an increasing interest in replacing CY with alternative non-chemotherapy agents. One such alternative is plerixafor, which is safe and well-tolerated by pts who cannot mobilize sufficient SC when the G-CSF+CY combination is used.

Jaakko Valtola from the Kuopio University Hospital, Kuopio, Finland, and collaborators, compared the cellular composition of apheresis products, the immunological recovery as well as the long-term outcome of MM pts mobilized with plerixafor and G-CSF, with or without CY, (plerixafor group), with those mobilized with G-CSF and CY (control group). The results of this non-randomized, multi-center, prospective study were published in the journal Leukemia & Lymphoma in August 2018.

Study Design:

• Number of pts = 87
• Plerixafor group: n = 10 pts; median age = 63 (range, 52–71); male/female = 5/5
• Control group: n = 77 pts; median age = 64 (range, 49–73); male/female = 40/37
• Mobilization with plerixafor and G-CSF: n = 3/60 pts (5%); G-CSF dose = 10 μg/kg/day until completion of apheresis
• Mobilization with plerixafor and CY+G-CSF: n = 7/27 pts (26%); CY dose = 2 g/m²; G-CSF dose = 5 μg/kg
• Median plerixafor dose = 17 mg (range, 12–24 mg)
• Time of plerixafor administration = 10 pm, with the exception of two pts who received it at 6 am
• Reasons for using plerixafor: not sufficient CD34⁺ cells to initiate apheresis, n = 6 pts; decreasing blood CD34⁺ counts, n = 2 pts; previous collection yields not satisfactory, n = 2 pts

Key Data:

Results are presented as plerixafor group vs control group

• Median number of apheresis = 2 (range, 1–4), P = 0.86
• Median number of CD34⁺ cells collected= 6.0 x 10⁶ cell/kg (range, 2.3–10.3) vs 6.4 x 10⁶ cell/kg (range, 2.0–17.9), P = 0.436
• After cryopreservation the number of CD34⁺ cells were similar between the total collection yields and the grafts used after high-dose therapy (HDT)
• Significantly more total numbers (x 10⁶ cell/kg) of T and B lymphocytes in the plerixafor vs the control group for both collected grafts and grafts used at HDT (values below are for collected grafts):
  • T lymphocytes = 292.7 (range, 58.3–683.6) vs 89.4 (range, 5.5–496.5), P < 0.001
  • CD3⁺ CD4⁺ lymphocytes = 206.2 (range, 37.6–502.5) vs 54.8 (range, 3.4–249.9), P < 0.001
  • CD3⁺ CD8⁺ lymphocytes = 86.6 (range, 21.2–194.1) vs 25.6 (range, 1.5–242.9), P = 0.004
  • CD19⁺ B cells = 17.7 (range, 1.7–76.7) vs  2.2 (range, 0.01–61.59), P = 0.001
  • NK cells = 28.3 (range, 2.3–65.3) vs 9.2 (range, 0.5–144.7), P = 0.015
• Similar apheresis yields between the plerixafor/G-CSF and plerixafor/CY+G-CSF
• Significantly more CD3⁺ CD4⁺ lymphocytes in mobilized grafts from the infused plerixafor/G-CSF group vs the G-CSF alone group [131.6 x 10⁶ cell/kg (range, 18.8–266.2) vs 62.0 x 10⁶ cell/kg (range, 14.7–153.1), P = 0.048]
• Neutrophil engraftment (0.5 x 10⁹ cell/l) = 14 days vs 12 days, P = 0.002
• Platelet engraftment (≥ 20 x 10⁹ cell/l without transfusions) = 13 days vs 12 days, P = 0.618
• Absolute lymphocyte count at day 15 after the ASCT (ALC-15) = 0.6 x 10⁹ cell/l (range, 0.2–1.5) vs 0.5 x 10⁹ cell/l (range, 0.07–3.74), P = 0.321
• Percentage of pts who achieved ALC-15 ≥ 0.5 x 10⁹ cell/l = 75% vs 57%, P = 0.455
• Median time spent at hematology ward during HDT and ASCT = 21 vs 18 days, P = 0.029
• Bacteremia = 1/10 pts (10%) vs 19/77 pts (26%)
• Pts needing treatment at the intensive care unit = none
• Early (< 100 days) treatment-related deaths = none
• Similar hematological recovery between plerixafor and control groups
• Neutrophil level at day +15 after ASCT between plerixafor + G-CSF vs G-CSF alone = 2.2 x 10⁹ cell/l vs 1.6 x 10⁹ cell/l, P = 0.047
• Similar immunological recovery between plerixafor and control groups, with the exception of the significantly faster CD3⁺ CD4⁺ lymphocyte recovery in the plerixafor group at one month (0.45 x 10⁹ cell/l vs 0.27 10⁹ cell/l, P = 0.028) and three months (0.37 x 10⁹ cell/l vs 0.21 x 10⁹ cell/l, P = 0.008) after ASCT
• Median follow-up = 1,108 days (range, 342–1,654) vs 1,212 days (range, 139–1,928)
• Number of pts with disease relapse or progression = 6/10 (60%) vs 46/77 (60%), P = 0.633
• Median time to progression = 791 vs 449 days, P = 0.291
• Number of pts who have died during follow-up = 1/10 (10%) vs 16/77 (21%), P = 0.679
• Median time to progression between plerixafor + G-CSF (4 pts)  vs G-CSF alone (10 pts) = 569 days vs 379 days, P = 0.839

Conclusions

The composition of the apheresis products was significantly increased in terms of the number of T and B lymphocytes and NK cells, in the group that was mobilized with plerixafor compared to the control group. However, these results need to be interpreted with caution, since the plerixafor group was small compared to the control group (10 vs 77 pts) and comprised of two differently treated subgroups: the plerixafor + G-CSF alone and the plerixafor + G-CSF/CY group. The study is in agreement with the safety of plerixafor as a mobilization agent and supports its use when the combination of G-CSF/CY is not well-tolerated or is not efficient for mobilization.

References

Valtola J. et al. Blood graft composition and post-transplant recovery in myeloma patients mobilized with plerixafor: a prospective multicenter study. Leukemia & Lymphoma. 2018 Aug 30:1-9. DOI: 10.1080/10428194.2018.1485911. [Epub ahead of print].