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06-03-2024 | Daratumumab | Review

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

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

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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Kumar SK, Jacobus SJ, Cohen AD et al (2020) Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol 21:1317–1330. https://doi.org/10.1016/S1470-2045(20)30452-6CrossRefPubMedPubMedCentral

Morè S, Corvatta L, Manieri VM et al (2022) Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go? Cells 11:606. https://doi.org/10.3390/cells11040606CrossRefPubMedPubMedCentral

Attal M, Lauwers-Cances V, Hulin C et al (2017) Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. New England Journal of Medicine 376:1311–1320. https://doi.org/10.1056/NEJMoa1611750CrossRefPubMed

Al Hamed R, Bazarbachi AH, Malard F et al (2019) Current status of autologous stem cell transplantation for multiple myeloma. Blood Cancer J 9:44. https://doi.org/10.1038/s41408-019-0205-9CrossRefPubMedPubMedCentral

Mina R, Lonial S (2019) Is there still a role for stem cell transplantation in multiple myeloma? Cancer 125:2534–2543. https://doi.org/10.1002/cncr.32060CrossRefPubMed

Bazarbachi AH, Al Hamed R, Malard F et al (2022) Induction therapy prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma: an update. Blood Cancer J 12:47. https://doi.org/10.1038/s41408-022-00645-1CrossRefPubMedPubMedCentral

Cavo M, Gay F, Beksac M et al (2020) Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol 7:e456–e468. https://doi.org/10.1016/S2352-3026(20)30099-5CrossRefPubMed

Li S, Fu J, Ma H et al (2013) Lenalidomide-induced upregulation of CXCR4 in CD34+ hematopoietic cells, a potential mechanism of decreased hematopoietic progenitor mobilization. Leukemia 27:1407–1411. https://doi.org/10.1038/leu.2012.323CrossRefPubMed

Facon T, Kumar SK, Plesner T et al (2021) Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol 22:1582–1596. https://doi.org/10.1016/S1470-2045(21)00466-6CrossRefPubMed

10.

Dimopoulos MA, Oriol A, Nahi H et al (2023) Overall Survival With Daratumumab, Lenalidomide, and Dexamethasone in Previously Treated Multiple Myeloma (POLLUX): A Randomized, Open-Label, Phase III Trial. J Clin Oncol 41:1590–1599. https://doi.org/10.1200/JCO.22.00940CrossRefPubMedPubMedCentral

11.

Dimopoulos MA, Moreau P, Terpos E et al (2021) Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Hemasphere 5:e528. https://doi.org/10.1097/HS9.0000000000000528CrossRefPubMedPubMedCentral

12.

Mateos M-V, Hernández M-T, Giraldo P et al (2013) Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 369:438–447. https://doi.org/10.1056/NEJMoa1300439CrossRefPubMed

13.

Kumar S, Dispenzieri A, Lacy MQ et al (2007) Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 21:2035–2042. https://doi.org/10.1038/sj.leu.2404801CrossRefPubMed

14.

Paripati H, Stewart AK, Cabou S et al (2008) Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia 22:1282–1284. https://doi.org/10.1038/sj.leu.2405100CrossRefPubMed

15.

Bhutani D, Zonder J, Valent J et al (2013) Evaluating the effects of lenalidomide induction therapy on peripheral stem cells collection in patients undergoing autologous stem cell transplant for multiple myeloma. Support Care Cancer 21:2437–2442. https://doi.org/10.1007/s00520-013-1808-5CrossRefPubMed

16.

Ogunniyi A, Rodriguez M, Devlin S et al (2017) Upfront use of plerixafor and granulocyte-colony stimulating factor (GCSF) for stem cell mobilization in patients with multiple myeloma: efficacy and analysis of risk factors associated with poor stem cell collection efficiency. Leuk Lymphoma 58:1123–1129. https://doi.org/10.1080/10428194.2016.1239261CrossRefPubMed

17.

Laurent V, Fronteau C, Antier C et al (2021) Autologous stem-cell collection following VTD or VRD induction therapy in multiple myeloma: a single-center experience. Bone Marrow Transplant 56:395–399. https://doi.org/10.1038/s41409-020-01033-8CrossRefPubMed

18.

Kumar S, Flinn I, Richardson PG et al (2012) Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 119:4375–4382. https://doi.org/10.1182/blood-2011-11-395749CrossRefPubMed

19.

Popat U, Saliba R, Thandi R et al (2009) Impairment of filgrastim-induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma. Biol Blood Marrow Transplant 15:718–723. https://doi.org/10.1016/j.bbmt.2009.02.011CrossRefPubMedPubMedCentral

20.

Pozotrigo M, Adel N, Landau H et al (2013) Factors impacting stem cell mobilization failure rate and efficiency in multiple myeloma in the era of novel therapies: experience at Memorial Sloan Kettering Cancer Center. Bone Marrow Transplant 48:1033–1039. https://doi.org/10.1038/bmt.2012.281CrossRefPubMed

21.

Costa LJ, Abbas J, Hogan KR et al (2012) Growth factor plus preemptive ('just-in-time’) plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure. Bone Marrow Transplant 47:1403–1408. https://doi.org/10.1038/bmt.2012.60CrossRefPubMed

22.

Samaras P, Pfrommer S, Seifert B et al (2015) Efficacy of Vinorelbine Plus Granulocyte Colony–Stimulation Factor for CD34+ Hematopoietic Progenitor Cell Mobilization in Patients with Multiple Myeloma. Biol Blood Marrow Transplant 21:74–80. https://doi.org/10.1016/j.bbmt.2014.09.020CrossRefPubMed

23.

Dosani T, Covut F, Pinto R et al (2019) Impact of lenalidomide on collected hematopoietic myeloid and erythroid progenitors: peripheral stem cell collection may not be affected. Leuk Lymphoma 60:2199–2206. https://doi.org/10.1080/10428194.2019.1573367CrossRefPubMed

24.

Partanen A, Valtola J, Silvennoinen R et al (2017) Impact of lenalidomide-based induction therapy on the mobilization of CD34+ cells, blood graft cellular composition, and post-transplant recovery in myeloma patients: a prospective multicenter study. Transfusion 57:2366–2372. https://doi.org/10.1111/trf.14220CrossRefPubMed

25.

Xu L, Liu J, Huang B et al (2021) Comparison of efficacy, safety, patients’ quality of life, and doctors’ occupational stress between lenalidomide-based and bortezomib-based induction in patients with newly diagnosed multiple myeloma. Cancer Med 10:1656–1667. https://doi.org/10.1002/cam4.3762CrossRefPubMedPubMedCentral

26.

Cowan AJ, Stevenson PA, Green DJ et al (2021) Prolonged Lenalidomide Therapy Does Not Impact Autologous Peripheral Blood Stem Cell Mobilization and Collection in Multiple Myeloma Patients: A Single-Center Retrospective Analysis. Transplant Cell Ther 27:661.e1–661.e6. https://doi.org/10.1016/j.jtct.2021.04.010CrossRefPubMed

27.

Voorhees PM, Kaufman JL, Laubach J et al (2020) Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood 136:936–945. https://doi.org/10.1182/blood.2020005288CrossRefPubMedPubMedCentral

28.

Moreau P, Attal M, Hulin C et al (2019) Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet 394:29–38. https://doi.org/10.1016/S0140-6736(19)31240-1CrossRefPubMed

29.

Manjappa S, Fox R, Reese J et al (2020) Impact of Daratumumab on Stem Cell Collection, Graft Composition and Engraftment Among Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplant. Blood 136:35–37. https://doi.org/10.1182/blood-2020-142115CrossRef

30.

Ghose J, Viola D, Terrazas C et al (2018) Daratumumab induces CD38 internalization and impairs myeloma cell adhesion. Oncoimmunology 7:e1486948. https://doi.org/10.1080/2162402X.2018.1486948CrossRefPubMedPubMedCentral

31.

Quarona V, Ferri V, Chillemi A et al (2015) Unraveling the contribution of ectoenzymes to myeloma life and survival in the bone marrow niche. Ann N Y Acad Sci 1335:10–22. https://doi.org/10.1111/nyas.12485ADSCrossRefPubMed

32.

Al Saleh AS, Sidiqi MH, Gertz MA et al (2020) Delayed neutrophil engraftment in patients receiving Daratumumab as part of their first induction regimen for multiple myeloma. Am J Hematol 95:E8–E10. https://doi.org/10.1002/ajh.25654CrossRefPubMed

33.

Hulin C, Offner F, Moreau P et al (2021) 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 106:2257–2260. https://doi.org/10.3324/haematol.2020.261842CrossRefPubMedPubMedCentral

34.

Luan D, Christos PJ, Ancharski M et al (2020) Timing of Daratumumab Administered Pre-Mobilization in Multiple Myeloma Impacts Pre-Harvest Peripheral Blood CD34+ Cell Counts and Plerixafor Use. Blood 136:15–16. https://doi.org/10.1182/blood-2020-140811CrossRef

35.

Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Rev Esp Cardiol (Engl Ed) 74:790–799. https://doi.org/10.1016/j.rec.2021.07.010CrossRefPubMed

36.

Voorhees PM, Rodriguez C, Reeves B et al (2021) Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN. Blood Adv 5:1092–1096. https://doi.org/10.1182/bloodadvances.2020003642CrossRefPubMedPubMedCentral

37.

Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14:135. https://doi.org/10.1186/1471-2288-14-135CrossRefPubMedPubMedCentral

38.

Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13. https://doi.org/10.1186/1471-2288-5-13CrossRefPubMedPubMedCentral

39.

McGrath S, Sohn H, Steele R, Benedetti A (2020) Meta-analysis of the difference of medians. Biom J 62:69–98. https://doi.org/10.1002/bimj.201900036MathSciNetCrossRefPubMed

40.

Lo C, Mertz D, Loeb M (2014) Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol 14:1–5. https://doi.org/10.1186/1471-2288-14-45CrossRef

41.

Balduzzi S, Rücker G, Schwarzer G (2019) How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health 22:153–160. https://doi.org/10.1136/ebmental-2019-300117CrossRefPubMedPubMedCentral

42.

Hopman RK, DiPersio JF (2014) Advances in stem cell mobilization. Blood Rev 28:31–40. https://doi.org/10.1016/j.blre.2014.01.001CrossRefPubMedPubMedCentral

43.

Giralt S, Costa L, Schriber J et al (2014) Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biol Blood Marrow Transplant 20:295–308. https://doi.org/10.1016/j.bbmt.2013.10.013CrossRefPubMed

44.

Pulte D, Jansen L, Castro FA et al (2015) Trends in survival of multiple myeloma patients in Germany and the United States in the first decade of the 21st century. Br J Haematol 171:189–196. https://doi.org/10.1111/bjh.13537CrossRefPubMed

45.

Shah SR, Tran TM (2007) Lenalidomide in myelodysplastic syndrome and multiple myeloma. Drugs 67:1869–1881. https://doi.org/10.2165/00003495-200767130-00005CrossRefPubMed

46.

Hoy SM (2017) Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Drugs 77:1897–1908. https://doi.org/10.1007/s40265-017-0833-yCrossRefPubMed

47.

van der Veer MS, de Weers M, van Kessel B et al (2011) Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. Haematologica 96:284–290. https://doi.org/10.3324/haematol.2010.030759CrossRefPubMed

48.

Costa LJ, Chhabra S, Medvedova E et al (2022) Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma. J Clin Oncol 40:2901–2912. https://doi.org/10.1200/JCO.21.01935CrossRefPubMed

49.

Leypoldt LB, Tichy D, Besemer B et al (2024) Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma. J Clin Oncol 42:26–37. https://doi.org/10.1200/JCO.23.01696CrossRefPubMed

50.

Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma | NEJM. https://www.nejm.org/doi/full/10.1056/NEJMoa2312054. Accessed 1 Feb 2024

51.

Kumar S, Giralt S, Stadtmauer EA et al (2009) Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens. Blood 114:1729–1735. https://doi.org/10.1182/blood-2009-04-205013CrossRefPubMed

52.

Sebastien B, Cheverton P, Magnin C et al (2022) Development and validation of a predictive model to guide the use of plerixafor in pediatric population. Bone Marrow Transplant 57:1827–1832. https://doi.org/10.1038/s41409-022-01831-2CrossRefPubMedPubMedCentral

53.

Yu B, Jiang T, Liu D (2020) BCMA-targeted immunotherapy for multiple myeloma. J Hematol Oncol 13:125. https://doi.org/10.1186/s13045-020-00962-7CrossRefPubMedPubMedCentral

54.

Lancman G, Sastow DL, Cho HJ et al (2021) Bispecific Antibodies in Multiple Myeloma: Present and Future. Blood Cancer Discov 2:423–433. https://doi.org/10.1158/2643-3230.BCD-21-0028CrossRefPubMedPubMedCentral

55.

Mark T, Stern J, Furst JR et al (2008) Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant 14:795–798. https://doi.org/10.1016/j.bbmt.2008.04.008CrossRefPubMedPubMedCentral

Title: Effect of prior lenalidomide or daratumumab exposure on hematopoietic stem cell collection and reconstitution in multiple myeloma
Authors: Hongpeng Duan
Qiuhui Jiang
Long Liu
Manman Deng
Qian Lai
Yuelong Jiang
Zhifeng Li
Bing Xu
Zhijuan Lin
Publication date: 06-03-2024
Publisher: Springer Berlin Heidelberg
Keywords: Daratumumab
Multiple Myeloma
Filgrastim
Filgrastim
Published in: Annals of Hematology
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-024-05683-2

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