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Table of Contents
LETTER TO EDITOR
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 428-429

Inferior outcomes with plerixafor mobilization for autologous transplantation in myeloma: Probably not applicable to resource-constrained settings


Department of Clinical Hematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Date of Submission12-Apr-2021
Date of Decision14-Apr-2021
Date of Acceptance17-Apr-2021
Date of Web Publication30-Jun-2021

Correspondence Address:
Suvir Singh
Department of Clinical Hematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana - 141 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_74_21

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How to cite this article:
Singh S, Sharma R. Inferior outcomes with plerixafor mobilization for autologous transplantation in myeloma: Probably not applicable to resource-constrained settings. Cancer Res Stat Treat 2021;4:428-9

How to cite this URL:
Singh S, Sharma R. Inferior outcomes with plerixafor mobilization for autologous transplantation in myeloma: Probably not applicable to resource-constrained settings. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Jul 24];4:428-9. Available from: https://www.crstonline.com/text.asp?2021/4/2/428/320315



Shah et al. recently published a study in the American Journal of Hematology, in which they evaluated the outcomes of patients who underwent autologous stem cell transplantation (ASCT) for myeloma and received either granulocyte colony-stimulating factor (GCSF) alone (G) and GCSF along with plerixafor (G + P) for stem cell mobilization.[1] G + P was administered in a risk-adapted manner based on a preharvest CD34 count cutoff of <20/μl. Overall, 469 patients received G alone, and 141 received G + P for stem cell mobilization. The primary end point was the absolute lymphocyte count on day +30 (ALC-30), which was shown to predict the progression-free survival (PFS) at a threshold of >1000/μl. The secondary end points were PFS and overall survival (OS).

The baseline characteristics of the patients were well matched with regard to the age and pretransplant disease status (with a few caveats, listed below). Engraftment kinetics, including ALC-30 and time to neutrophil and platelet recovery, were similar in both the groups. Evaluation of the secondary end points revealed a similar PFS, but a strikingly shorter OS for the G + P group compared to the G group (44 vs. 73 months; 95% confidence interval, 3.2-not reached).

As discussed by the authors, mobilization failure in myeloma is seen in up to 23% of the patients, and the usage of plerixafor along with GCSF may be a harbinger of poorer long-term survival.[1] However, we would like to highlight three important caveats before accepting this inference and emphasize that a potential reduction in the survival with plerixafor should not dissuade the provision of ASCT to all eligible patients.

First, despite remarkable progress in the treatment of myeloma, ASCT continues to be the standard of care to this date and must be offered to all patients unless contraindicated.[2] The advent of several novel agents has challenged this ubiquitous recommendation, but this is yet to be proven in a randomized trial.[3],[4] Two randomized trials comparing ASCT with chemotherapy, namely, the EMN02/HO95 and IFM2009 trials, have shown a superior PFS for patients undergoing transplantation compared to those receiving chemotherapy alone.[5],[6]

Second, the lower survival observed in the G + P group in the above study may be suggestive of poorer disease biology and possibly patient status at the time of transplant. A greater number of patients in the G + P group received more than one line of treatment (33% vs. 20%, P = 0.003), and fewer patients got the full 200 mg/m2 dose of melphalan (58% vs. 69%, P = 0.020). In addition, the proportion of patients receiving lenalidomide maintenance was much smaller in the G + P group (46% vs. 57%, P = 0.034). This difference may have potentially offset the survival advantage conferred by the high-dose melphalan and post-ASCT lenalidomide maintenance.[7] A meta-analysis in 2019 showed that, even if the OS advantage with lenalidomide maintenance is debatable, a PFS advantage is certainly maintained.[8]

Third, the above equation changes in resource-limited settings, where ASCT is often the most cost-effective therapy for myeloma. Utility of ASCT as a disease control measure is paradoxically magnified, as the one-time cost is often lower than the continued cost of newer agents such as carfilzomib and daratumumab. ASCT has been shown to be cost effective compared to chemotherapy in India, if initiated early.[9] Transplant-related mortality, which was a major problem in the low- and middle-income countries (LMICs), has been overcome and ranges from 2% to 3% in the Indian setting.[10] The PFS advantage offered by ASCT in the Indian setting contradicts the Western data, ranging from 30 to 40 months, and is greater than that with most other salvage regimens.[11]

Myeloma has a nearly 100% risk of relapse after treatment, despite ASCT and requires the use of previously unused agents or combinations at each relapse. As agents for myeloma treatment in the second line and beyond are limited and progressively more expensive, an effective option like ASCT should be provided to as many patients as possible. Western data indicate that <20% of the eligible patients undergo ASCT, a number which is likely to be much lower in India.[12] In the LMICs, the cost of peripheral blood stem cell (PBSC) mobilization including apheresis kits, disposables, and the use of central venous access for certain patients is not negligible, and a 2nd-day harvest ostensibly adds to the same. In a private setup, the cost of the overall procedure may be higher. With the reducing costs and availability of noninnovator brands, plerixafor is increasingly becoming more cost effective compared to a 2nd-day harvest. As of 2020, a 24 mg dose of plerixafor costs approximately $300 (approximately $21,700), which is far lower than the cost and risks of a 2nd-day PBSC harvest. Our protocol of offering risk-adapted plerixafor for all patients on day 1 would likely be more cost effective in the long run than waiting for a 2nd-day harvest.

Therefore, it appears that plerixafor use in this study is a red herring for poor marrow function or suboptimally controlled disease and does not directly lead to inferior outcomes. Offering plerixafor along with GCSF judiciously may facilitate ASCT in patients who may not otherwise receive it and allow for better disease control in a cost-effective manner. We agree with the authors that there are significant lacunae in this area, and a head-to-head cost effectiveness comparison might help to define the role of G + P in myeloma. Cost saving will allow for better implementation of proven interventions such as maintenance therapy or salvage therapy at relapse in LMICs.

Financial support and sponsorship

Nil.



Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Shah H, Kim S, Singh P, Alavi A, Ratanatharathorn V, Ayash L, et al. Clinical outcomes of multiple myeloma patients who undergo autologous hematopoietic stem cell transplant with G-CSF or G-CSF and plerixafor mobilized grafts. Am J Hematol 2020;95:198-204.  Back to cited text no. 1
    
2.
Dhakal B, Szabo A, Chhabra S, Hamadani M, D'Souza A, Usmani SZ, et al. Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction: A systematic review and meta-analysis. JAMA Oncol 2018;4:343-50.  Back to cited text no. 2
    
3.
Al Hamed R, Bazarbachi AH, Malard F, Harousseau JL, Mohty M. Current status of autologous stem cell transplantation for multiple myeloma. Blood Cancer J 2019;9:44.  Back to cited text no. 3
    
4.
Bagal B, Bonda A. Induction therapy in newly diagnosed multiple myeloma: Current research scenario and questions for the future. Cancer Res Stat Treat 2019;2:76-82.  Back to cited text no. 4
  [Full text]  
5.
Cavo M, Petrucci MT, Di Raimondo F, Zamagni E, Gamberi B, Crippa C, et al. Upfront single versus double autologous stem cell transplantation for newly diagnosed multiple myeloma: An intergroup, multicenter, phase III study of the European Myeloma Network (EMN02/HO95 MM Trial). Blood 2016;128:991.  Back to cited text no. 5
    
6.
Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med 2017;376:1311-20.  Back to cited text no. 6
    
7.
McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366:1770-81.  Back to cited text no. 7
    
8.
Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, et al. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): A multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2019;20:57-73.  Back to cited text no. 8
    
9.
Prinja S, Kaur G, Malhotra P, Jyani G, Ramachandran R, Bahuguna P, et al. Cost-Effectiveness of autologous stem cell treatment as compared to conventional chemotherapy for treatment of multiple myeloma in India. Indian J Hematol Blood Transfus 2017;33:31-40.  Back to cited text no. 9
    
10.
Kulkarni U, Devasia AJ, Korula A, Fouzia NA, Nisham PN, Samoon YJ, et al. Clinical outcomes in multiple myeloma post-autologous transplantation-a single centre experience. Indian J Hematol Blood Transfus 2019;35:215-22.  Back to cited text no. 10
    
11.
Kumar L, Ramavath D, Kataria B, Tiwari A, Raj A, Chellapuram SK, et al. High-dose chemotherapy followed by autologous stem cell transplant for multiple myeloma: Predictors of long-term outcome. Indian J Med Res 2019;149:730-9.  Back to cited text no. 11
[PUBMED]  [Full text]  
12.
Chute JP. Autologous stem cell transplantation for multiple myeloma: Underutilized but highly effective. J Natl Cancer Inst 2019;111:7-8.  Back to cited text no. 12
    




 

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