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Effect of prior lenalidomide or daratumumab exposure on hematopoietic stem cell collection and reconstitution in multiple myeloma

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Abstract

Background

The roles of Lenalidomide (Len) and Daratumumab (Dara) in multiple myeloma treatment are well-established, yet their influences on hematopoietic stem cell harvesting and reconstitution remain disputed.

Methods

We conducted a systematic database review to identify cohort studies or RCTs evaluating the effect of the use of Len or Dara on hematopoietic stem cell collection and peripheral blood count recovery in multiple myeloma patients. Effects on hematopoietic collection or reconstitution were estimated by comparing standardized mean differences (SMD) and mean differences (MD), or median differences.

Results

Eighteen relevant studies were identified, summarizing mobilization results. For Len, data from 13 studies were summarized, including total CD34+ cell yield, collection failure rate, and time to neutrophil and platelet engraftment. Results indicated that Len exposure led to decreased stem cell collection [SMD=-0.23, 95% CI (-0.34, -0.12)]. However, collection failure (<2×106) could be mitigated by plerixafor [OR=2.14, 95% CI (0.96, 4.77)]. For Dara, two RCTs and three cohort studies were included, showing that Dara exposure resulted in a reduction in total stem cells even with optimized plerixafor mobilization [SMD=-0.75, 95% CI (-1.26, -0.23)], and delayed platelet engraftment recovery [MD=1.20, 95% CI (0.73, 1.66)].

Conclusions

Our meta-analysis offers a comprehensive view of Len and Dara's impacts on hematopoietic stem cell collection and reconstitution in multiple myeloma. Len usage could lead to reduced stem cell collection, counteracted by plerixafor mobilization. Dara usage could result in diminished stem cell collection and delayed platelet engraftment.

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Data availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

NDMM :

newly diagnosed multiple myeloma

ASCT :

autologous stem cell transplantation

PIs :

proteasome inhibitors

IMiDs :

immunomodulatory agents

Len/R :

lenalidomide

Dara :

daratumumab

SMD :

standardized mean difference

MD :

mean differences

qe :

quantile estimation

CI :

confidence interval

OS :

overall survival

CY :

cyclophosphamide

G-CSF :

granulocyte-colony stimulating factor

ANC :

absolute neutrophil count

PLT :

platelets

Btz :

bortezomib

thal/T :

thalidomide

Dex/D :

dexamethasone

VAD :

vincristine-Adriamycin-dexamethasone

VDCR :

bortezomib (V), dexamethasone (D), lenalidomide (R) and cyclophosphamide (C)

CVAMP :

cyclophosphamide, vincristine, doxorubicin, methylprednisolone

PAD :

bortezomib, doxorubicin and dexamethasone

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Acknowledgments

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Funding

This work was financially supported by the National Natural Science Foundation of China (82000218 granted for Zhijuan Lin, U22A20290 and 82170180 granted for Bing Xu) and the Natural Science Foundation of Fujian Province (2020J01222713 granted for Zhijuan Lin, 2020J011246 granted for Bing Xu, 2020GGB054 granted for Zhifeng Li). Xiamen Municipal Bureau of Science and Technology (3502Z20209003 granted for Bing Xu, 3502Z20209008 granted for Zhifeng Li); The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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Authors and Affiliations

  1. Department of Hematology, School of Medicine, The First Affiliated Hospital of Xiamen University and Institute of Hematology, Xiamen University, Xiamen, 361102, People’s Republic of China

    Hongpeng Duan, Qiuhui Jiang, Long Liu, Manman Deng, Qian Lai, Yuelong Jiang, Zhifeng Li, Bing Xu & Zhijuan Lin

  2. Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, 361102, People’s Republic of China

    Hongpeng Duan, Qiuhui Jiang, Long Liu, Manman Deng, Qian Lai, Yuelong Jiang, Zhifeng Li, Bing Xu & Zhijuan Lin

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Contributions

HPD, ZJL and BX conceived and designed the study. HPD, ZJL and BX selected the articles and extracted and cross-checked the data. HPD, LL, ZFL, MMD, QL and YLJ contributed to the statistical analysis. HPD and ZJL wrote the first draft of the manuscript. HPD, QHJ, and XB revised and discussed the final edition. All authors read and approved the final manuscript.

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Correspondence to Bing Xu or Zhijuan Lin.

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Supplementary information

ESM 1

Supplementary figure 1 Hematopoietic stem cell collection failure due to lenalidomide (<2×106) (PNG 19 kb)

ESM 2

Supplementary figure 2 Suboptimal outcome of hematopoietic stem cell collection due to Dara (<4×106) (PNG 8 kb)

ESM 3

Supplementary figure 3 Quality assessment of the included studies (RCT) (PNG 5 kb)

ESM 4

Supplementary Table 1. Quality assessment of the included studies. Supplementary Table 2. Summary of the results of lenalidomide studies on the effects of hematopoietic reconstitution (ANC). Supplementary Table 3. Summary of the results of lenalidomide studies on the effects of hematopoietic reconstitution (PLT). Supplementary Table 4. Summary of the results of daratumumab studies on the effects of hematopoietic reconstitution (ANC). Supplementary Table 5. Summary of the results of daratumumab studies on the effects of hematopoietic reconstitution (PLT). Supplementary Table 6. Strategies for the use of Plerixafor (DOCX 24 kb)

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Duan, H., Jiang, Q., Liu, L. et al. Effect of prior lenalidomide or daratumumab exposure on hematopoietic stem cell collection and reconstitution in multiple myeloma. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05683-2

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