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Letters to the Editor
Table 1. Stem cell mobilization, harvesting, and transplantation. Patients with stem cell mobilization
PBSC mobilizing agents, n (%)a Cyclophosphamide/G-CSF Plerixafor
PBSC apheresis performed, n (%)
Patients with PBSC apheresis performed
Number of days of apheresis, mean [SD] (range)
Number of days of apheresis, n (%) 1
2 3 4 5 6
D-VTd
N=506
506 (100) 110 (21.7) 504 (99.6)c N=504 1.9 [0.92] (1–6)
184 (36.5) 204 (40.5) 91 (18.1) 18 (3.6)
VTd
N=492
492 (100) 39 (7.9) 490 (99.6)d N=490 1.4 [0.67] (1–4)
327 (66.7) 125 (25.5) 32 (6.5) 6 (1.2)
P
<0.0001b >0.999b
<0.0001e <0.0001f
<0.0001e
0.2494b <0.0001b <0.0001b 0.0758b <0.0001e
3(0.6) 0 Total number of CD34+ stem cells collected (106/kg) among patients with PBSC apheresis performed
Mean [SD] (range) ≥2 × 106/kg, n (%)
6.7 [2.63] (0.5–18.7) 501 (99.4) 444 (88.1) 380 (75.4) 489 (97.0) 3.6 [1.59] (0.5–12.6)
10.0 [5.25] (2.2–36.9) 490 (100) 470 (95.9) 434 (88.6) 484 (98.8) 5.0 [2.80] (1.2–23.3)
≥4 × 106/kg, n (%)
≥5 × 106/kg, n (%)
Patients who underwent transplantation, n (%)
Number of CD34+ stem cells transplanted (106/kg), Mean [SD] (range)
Percentages were calculated with N in each group as the denominator. aSeveral PBSC mobilizing agents were possible. bP-value calculated from Fisher’s exact test. cBone marrow harvest was performed for one patient in the D-VTd arm and no patients in theVTd arm.No patients had only bone marrow collection.The D-VTd patient received a stem cell collection from bone marrow in addition to apheresis from peripheral blood. Here both numbers are summed as a total of CD34+ stem cells collected from this patient. dBased on available information from the investigator, one patient in the VTd arm had successful CD34+ stem cell collection without a record of mobilization treatment. However, unrecorded mobilization likely occurred, although details are undocumented. eP-value calculated from two-sample t-test. fP-value calculated from Cochran-Armitage trend test. D-Vtd: daratumumab/bortezomib/thalidomide/dexamethasone; Vtd: bortezomib/thalidomide/dexamethasone; PBSC: peripheral blood stem cell; G-CSF: granulocyte colony-stimulating factor; SD: standard deviation.
mobilization with cyclophosphamide (recommended dose, 3 g/m2) and granulocyte colony-stimulating factor (G-CSF) (recommended dose, 10 mg/kg/day until the last day of the collection for a maximum of 10 days) after cycle 4. The recommended cyclophosphamide dose (3 g/m2) was not mandatory and varied by region (e.g., more patients received 2 g/m2 in the Netherlands and Belgium, while more received 3 g/m2 in France). Plerixafor use was permitted per institutional practice in case of failure. Peripheral blood stem cells were harvested based on response to mobilization. Patients underwent conditioning with intravenous melphalan 200 mg/m2 prior to ASCT. Per protocol, sufficient stem cells should be harvested to enable multiple transplants, in accor- dance with institutional standards. Cell counting after harvesting was conducted locally, per institutional prac- tice. Consolidation therapy was initiated after hematopoietic reconstitution, but not earlier than 30 days after transplantation. Intergroupe Francophone du Myélome and Janssen statisticians were involved in all stages of the study and data analysis.
A total of 1,085 patients were randomized to D-VTd (n=543) or VTd (n=542) (Figure 1). Results for stem cell mobilization, harvesting, and transplantation are pre- sented in Table 1. At the clinical cutoff of June 19, 2018, among those undergoing induction (D-VTd, n=536; VTd, n=538), 506 (94.4%) patients in the D-VTd group and 492 (91.4%) patients in the VTd group received
cyclophosphamide/G-CSF; 504 (94.0%) and 490 (91.1%) patients, respectively, underwent stem cell harvesting. Plerixafor was administered in the course of stem cell mobilization to 110 patients (21.7% of the 506 patients who underwent mobilization) in the D-VTd group versus 39 patients (7.9% of the 492 patients who underwent mobilization) in the VTd group (P<0.0001). One patient who received VTd had no record of mobilization treat- ment but had successful collection of CD34+ cells from peripheral blood in 2 consecutive days of apheresis; this patient received HDT with stem cell transplant with engraftment. One patient in the D-VTd group had stem cells collected from bone marrow in addition to apheresis from peripheral blood. Five patients (D-VTd, n=2; VTd, n=3) who received mobilizing agents did not undergo stem cell harvesting; of these, mobilization failure was noted in three patients (D-VTd, n=2; VTd, n=1). The two patients in the D-VTd group who failed mobilization underwent two mobilization procedures and failed both. The single patient in the VTd group who failed mobiliza- tion did not have a second procedure. The remaining two patients in the VTd group who received mobilizing agents did not undergo stem cell harvest and discontin- ued treatment due to death (n=1; serious adverse event of large intestine perforation with a history of sigmoid diverticulosis) or disease progression (n=1).
The mean number of days of apheresis were 1.9 for D- VTd versus 1.4 for VTd (P<0.0001; Table 1). Apheresis
4(0.8) 0
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