Long-term outcomes of innovator versus generic melphalan formulation in autologous hematopoietic cell transplantation for multiple myeloma.


Journal

Hematology/oncology and stem cell therapy
ISSN: 2589-0646
Titre abrégé: Hematol Oncol Stem Cell Ther
Pays: Saudi Arabia
ID NLM: 101468532

Informations de publication

Date de publication:
Jun 2021
Historique:
received: 14 05 2020
revised: 08 06 2020
accepted: 09 06 2020
pubmed: 6 7 2020
medline: 16 6 2021
entrez: 6 7 2020
Statut: ppublish

Résumé

Most data on autologous hematopoietic cell transplantation (auto-HCT) in myeloma are based on the use of innovator formulation of melphalan. Comparative bioequivalence and efficacy studies of generic melphalan are lacking. In this retrospective study, we report long-term outcomes of auto-HCT in myeloma using innovator (Alkeran, Aspen Pharma; n = 41) and generic melphalan (Alkacel, Celon Labs, India; n = 55) formulations. All consecutive patients at a single center from the period 2011-2018 were included. The median follow-up in the innovator and generic groups was 61.7 and 32.5 months, respectively. Both groups were matched for age, sex, stage, and myeloma response. There were significantly more patients in the innovator melphalan group who were administered melphalan at a reduced dose at physician discretion (26.8% vs. 3.6%, p = .001). There were significantly more patients with grade 3 or higher mucositis (68.3% vs. 38.1%, p < .0001) and grade 3 or higher diarrhea (85.4% vs. 50.1%, p < .0001) in the innovator group. The median duration of hospital stay was significantly longer in the innovator group (19 days vs. 15.5 days, p < .0001). There were significantly more patients in the generic group who received standard maintenance (94.5% vs. 34.1%, p < .0001). Despite the differences in the melphalan dose and post-transplant strategies, the 4-year progression-free survival and overall survival were not significantly different in the two groups (58% vs. 63%, p = .7, 71% vs. 72%, p = .4, respectively). Long-term efficacy comparison is helpful in the absence of postmarketing bioequivalence studies of generic melphalan.

Sections du résumé

BACKGROUND BACKGROUND
Most data on autologous hematopoietic cell transplantation (auto-HCT) in myeloma are based on the use of innovator formulation of melphalan. Comparative bioequivalence and efficacy studies of generic melphalan are lacking.
METHODS METHODS
In this retrospective study, we report long-term outcomes of auto-HCT in myeloma using innovator (Alkeran, Aspen Pharma; n = 41) and generic melphalan (Alkacel, Celon Labs, India; n = 55) formulations. All consecutive patients at a single center from the period 2011-2018 were included.
RESULTS RESULTS
The median follow-up in the innovator and generic groups was 61.7 and 32.5 months, respectively. Both groups were matched for age, sex, stage, and myeloma response. There were significantly more patients in the innovator melphalan group who were administered melphalan at a reduced dose at physician discretion (26.8% vs. 3.6%, p = .001). There were significantly more patients with grade 3 or higher mucositis (68.3% vs. 38.1%, p < .0001) and grade 3 or higher diarrhea (85.4% vs. 50.1%, p < .0001) in the innovator group. The median duration of hospital stay was significantly longer in the innovator group (19 days vs. 15.5 days, p < .0001). There were significantly more patients in the generic group who received standard maintenance (94.5% vs. 34.1%, p < .0001). Despite the differences in the melphalan dose and post-transplant strategies, the 4-year progression-free survival and overall survival were not significantly different in the two groups (58% vs. 63%, p = .7, 71% vs. 72%, p = .4, respectively).
CONCLUSION CONCLUSIONS
Long-term efficacy comparison is helpful in the absence of postmarketing bioequivalence studies of generic melphalan.

Identifiants

pubmed: 32622756
pii: S1658-3876(20)30113-8
doi: 10.1016/j.hemonc.2020.06.002
pii:
doi:

Substances chimiques

Antineoplastic Agents, Alkylating 0
Drugs, Generic 0
Myeloablative Agonists 0
Melphalan Q41OR9510P

Types de publication

Comparative Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114-118

Informations de copyright

Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Part of this work was funded by the Science and Engineering Research Board, Department of Science and Technology, Government of India (file number ECR/2016/000884) grant to DPL and ANP. All the other authors have no competing financial interests to disclose.

Auteurs

Deepesh P Lad (DP)

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address: deepesh.lad12@gmail.com.

Pankaj Malhotra (P)

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Amol N Patil (AN)

Department of Clinical Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Ram V Nampoothiri (RV)

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Kripa Shanker Kasudhan (KS)

Department of Clinical Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Alka Khadwal (A)

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Gaurav Prakash (G)

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Arihant Jain (A)

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Samir Malhotra (S)

Department of Clinical Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Neelam Varma (N)

Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Savita Verma Attri (SV)

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Subhash Varma (S)

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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Classifications MeSH