Cytarabine + G-CSF is more effective than cyclophosphamide + G-CSF as a stem cell mobilization regimen in multiple myeloma

Jelı́nek, Tomáš; Adamusova, Lucie; Popková, Tereza; Tvrdá, Ivana; Smejkalová, Jana; Šimíček, Michal; Šalounová, Dana; Kaščák, Michal; Mihályová, Jana; Plonková, Hana; Ďuraš, Juraj; Navrátil, Milan; Kořístek, Zdeněk

doi:10.1038/s41409-018-0396-x

Cited by 12 publications

(21 citation statements)

References 32 publications

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“…Furthermore, the mean number of apheresis performed to obtain the product was lower in Ara-C group compared to patients treated with a Cy regimen (1.2 vs 2.1). 30 Our results confirm these observations as the number of harvested HSCs was significantly higher in the Ara-C group compared with the Cy group. Enhanced efficiency of Ara-C is also demonstrated by the fact that all but one patient obtained 4 × 10 6 cells/kg of CD34+ cell, a yields sufficient for tandem transplant, while 63% of those in the Cy group failed to reach this level.…”

Section: Discussionsupporting

confidence: 86%

“…In the retrospective data analysis conducted by Jelinek et al, of a group of 70 MM patients who underwent HSC mobilization, 98% of those mobilized with Ara‐C and G‐CSF achieved a target yield of 10 × 10 6 CD34+ cells/kg, while only 67% of patients in the Cy cohort harvested the number of cells adequate for transplantation. Furthermore, the mean number of apheresis performed to obtain the product was lower in Ara‐C group compared to patients treated with a Cy regimen (1.2 vs 2.1) 30 …”

Section: Discussionmentioning

confidence: 87%

“…Moreover, the time to neutrophil and platelets recovery after ASCT was much shorter in the second group 24 . Similarly, Ara‐C has proved to be more effective than Cy in studies carried out by two other groups 21,30 . Ara‐C combined with G‐CSF resulted in higher numbers of harvested stem cells than Cy with G‐CSF, with up to 81% to 95% patients achieving CD34+ cells level adequate for tandem transplantation, 10 including previous poor mobilizers 23 .…”

Section: Discussionmentioning

confidence: 98%

“…24 Similarly, Ara-C has proved to be more effective than Cy in studies carried out by two other groups. 21,30 Ara-C combined with G-CSF resulted in higher numbers of harvested stem cells than Cy with G-CSF, with up to 81% to 95% patients achieving CD34+ cells level adequate for tandem transplantation, 10 including previous poor mobilizers. 23 In the retrospective data analysis conducted by Jelinek et al, of a group of 70 MM patients who underwent HSC mobilization, 98% of those mobilized with Ara-C and G-CSF achieved a target yield of 10 × 10 6 CD34+ cells/kg, while only 67% of patients in the Cy cohort harvested the number of cells adequate for transplantation.…”

Section: Discussionmentioning

confidence: 99%

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Higher efficacy of intermediate dose cytarabine + G‐CSF compared to cyclophosphamide + G‐CSF in hematopoietic stem cell mobilization in patients with multiple myeloma

Bogucka-Fedorczuk

Czyż

Kalicińska

et al. 2020

J of Clinical Apheresis

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Background There are several regimens used in hematopoietic stem cell (HSC) mobilization in multiple myeloma (MM). Cyclophosphamide (Cy) is one of the most commonly used agents, although it does not always result in collecting adequate number of CD34+ cells. Recently, cytarabine (Ara‐C) has been proposed as potentially efficient and safe option. Aims Since the data regarding Ara‐C in HSC mobilization is limited, the aim of our study was to compare retrospectively the efficiency and toxicity of G‐CSF combined with either Ara‐C or Cy in MM patients. Materials & Methods Of a total of 89 patients, 43 received low or intermediate doses of Cy, and 46 were treated with 800 mg/m2/day of Ara‐C administered for two days. Results The mean peak of CD34+ cells/ul in peripheral blood was 132 (range, 84‐202) in Ara‐C and 51 (range, 29‐69) in Cy cohort (p < 0.001). The median number of collected CD34+ cells (×106/kg) was 10.3 (range, 4.2‐17.9) vs 4.5 (range, 2.7‐8.9), respectively (p < 0.001). Mobilization failure was observed in one patient in Ara‐C cohort (2%) and in 8 patients treated with Cy (19%) (p = 0.013). In the Ara‐C group 98% of patients obtained more than 4×106 CD34+ cells/kg required for tandem transplantation. Moreover, we observed a trend toward increased paraprotein levels measured at transplant compared to before HSC mobilization in Ara‐C cohort and significantly higher transfusion rates in that group. Conclusion Our findings confirm higher HSC mobilization efficacy of Ara‐C compared to Cy in MM patients. However, lower transfusions rate and better disease control of Cy may justify its use in some cases.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Higher efficacy of intermediate dose cytarabine + G‐CSF compared to cyclophosphamide + G‐CSF in hematopoietic stem cell mobilization in patients with multiple myeloma

Bogucka-Fedorczuk

Czyż

Kalicińska

et al. 2020

J of Clinical Apheresis

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“…64 Other regimens including cytarabine plus G-CSF have been shown to result in better stem-cell yield than G-CSF alone 65 or cyclophosphamide plus G-CSF. 66 Patients can also be collected successfully on the rebound from intense chemotherapy when regimens like VDT PACE are employed for treatment of the disease. Despite the high cost of plerixafor, it is potentially cost-effective because of increased yield and reduced toxicities, therefore, reducing the need for additional G-CSF use and hospitalization.…”

Section: Mobilization and Stem-cell Collection For Asctmentioning

confidence: 99%

Stem-cell transplantation in multiple myeloma: how far have we come?

Soekojo

Kumar

2019

Therapeutic Advances in Hematology

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High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) has historically been an essential part of multiple myeloma (MM) management since early studies demonstrated its efficacy in relapsed disease, and subsequent phase III trials demonstrated better responses and improved survival with this modality compared with standard chemotherapy. With further advances in the MM treatment landscape, including the development of potent novel agents, there has been an increasing debate around various aspects of ASCT, including the optimal timing, role of single versus tandem ASCT, and the practice of consolidation and maintenance therapy post-ASCT. Routine incorporation of the novel agents at each of the treatment phases, induction, consolidation when used, and maintenance has led to better responses as reflected by increasing rates of minimal residual disease (MRD) negativity, longer progression-free survival (PFS) with improvement in overall survival (OS) and in some of the trials. The phase III trials over the last decade have provided significant clarity on the current approach, and have raised important questions regarding the applicability of this modality in all patients. This review aims to summarize the latest literature in the field and discusses how these findings impact the practice of ASCT today.

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Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma

Tang,

Li,

Zhang

et al. 2024

Cancer Medicine

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ObjectiveTQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first‐in‐human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM).MethodsThis is a multicenter phase I clinical trial consisting of the 3+3 dose‐escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28‐day cycle.ResultsTwenty‐five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose‐limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any‐grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time‐to‐plasma peak concentration of 0.8–1.5 h. The mean half‐life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response‐evaluable patients, 63.7% achieved stable disease or better.ConclusionsTQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose‐expansion phase.

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Cytarabine + G-CSF is more effective than cyclophosphamide + G-CSF as a stem cell mobilization regimen in multiple myeloma

Cited by 12 publications

References 32 publications

Higher efficacy of intermediate dose cytarabine + G‐CSF compared to cyclophosphamide + G‐CSF in hematopoietic stem cell mobilization in patients with multiple myeloma

Higher efficacy of intermediate dose cytarabine + G‐CSF compared to cyclophosphamide + G‐CSF in hematopoietic stem cell mobilization in patients with multiple myeloma

Stem-cell transplantation in multiple myeloma: how far have we come?

Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma

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