Molecular response after obinutuzumab plus high-dose cytarabine induction for transplant-eligible patients with untreated mantle cell lymphoma (LyMa-101): a phase 2 trial of the LYSA group.

Adolescent Adult Anemia / etiology Antibodies, Monoclonal, Humanized / administration & dosage Antineoplastic Combined Chemotherapy Protocols / adverse effects Area Under Curve Bone Marrow / pathology Cytarabine / administration & dosage Dexamethasone / administration & dosage Hematopoietic Stem Cell Transplantation Humans Lymphoma, Mantle-Cell / drug therapy Middle Aged Neoplasm, Residual Prospective Studies ROC Curve Transplantation, Autologous Treatment Outcome Young Adult

Journal

The Lancet. Haematology

ISSN: 2352-3026

Titre abrégé: Lancet Haematol

Pays: England

ID NLM: 101643584

Informations de publication

Date de publication:
Nov 2020

Historique:

received: 30 04 2020

revised: 24 07 2020

accepted: 24 07 2020

pubmed: 25 9 2020

medline: 30 10 2020

entrez: 24 9 2020

Statut: ppublish

Résumé

Obinutuzumab monotherapy has shown promising efficacy in mantle cell lymphoma. We aimed to investigate the activity of obinutuzumab plus DHAP (dexamethasone, high-dose cytarabine, and cisplatin), measured by minimal residual disease quantitative (q)PCR status in the bone marrow after four cycles. LyMa-101 was a prospective, open-label, single-arm, phase 2 trial. Participants were enrolled from 28 hospitals in France. Newly diagnosed patients with mantle cell lymphoma (aged 18 to <66 years) who were eligible for autologous stem-cell transplantation received four cycles of obinutuzumab plus DHAP (obinutuzumab 1000 mg/m 86 patients were enrolled between Nov 29, 2016, and May 2, 2018. 81 patients completed induction, 73 underwent autologous stem-cell transplantation, and 69 started maintenance therapy. 55 (75%) of 73 patients in the efficacy set reached minimal residual disease negativity in bone marrow at end of induction. According to the protocol definition, 18 (25%) of 73 patients in the efficacy set were minimal residual disease-positive: 12 patients who were minimal residual disease-positive in the bone marrow, plus two patients who progressed during induction, and four patients who did not have minimal residual disease assessment. The most common grade 3-4 treatment-emergent adverse events were anaemia (grade 3, 26 [31%] of 85 patients; grade 4, three [4%] of 85 patients) and neutropenia (grade 3, 13 [15%] of 85 patients; grade 4, 32 [38%] of 85 patients). 58 serious adverse events occurred during the induction phase. There were no treatment-related deaths. Obinutuzumab plus DHAP is a well tolerated regimen and has good activity for inducing minimal residual disease negativity in the bone marrow of transplant-eligible patients with mantle cell lymphoma. Obinutuzumab plus DHAP has potential activity as induction chemotherapy, with bone marrow minimal residual disease negativity potentially predicting long-term disease control. Roche SAS.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

LyMa-101 was a prospective, open-label, single-arm, phase 2 trial. Participants were enrolled from 28 hospitals in France. Newly diagnosed patients with mantle cell lymphoma (aged 18 to <66 years) who were eligible for autologous stem-cell transplantation received four cycles of obinutuzumab plus DHAP (obinutuzumab 1000 mg/m

FINDINGS RESULTS

86 patients were enrolled between Nov 29, 2016, and May 2, 2018. 81 patients completed induction, 73 underwent autologous stem-cell transplantation, and 69 started maintenance therapy. 55 (75%) of 73 patients in the efficacy set reached minimal residual disease negativity in bone marrow at end of induction. According to the protocol definition, 18 (25%) of 73 patients in the efficacy set were minimal residual disease-positive: 12 patients who were minimal residual disease-positive in the bone marrow, plus two patients who progressed during induction, and four patients who did not have minimal residual disease assessment. The most common grade 3-4 treatment-emergent adverse events were anaemia (grade 3, 26 [31%] of 85 patients; grade 4, three [4%] of 85 patients) and neutropenia (grade 3, 13 [15%] of 85 patients; grade 4, 32 [38%] of 85 patients). 58 serious adverse events occurred during the induction phase. There were no treatment-related deaths.

INTERPRETATION CONCLUSIONS

Obinutuzumab plus DHAP is a well tolerated regimen and has good activity for inducing minimal residual disease negativity in the bone marrow of transplant-eligible patients with mantle cell lymphoma. Obinutuzumab plus DHAP has potential activity as induction chemotherapy, with bone marrow minimal residual disease negativity potentially predicting long-term disease control.

FUNDING BACKGROUND

Roche SAS.

Identifiants

DOI: 10.1016/S2352-3026(20)30291-X PMID: 32971036

pubmed: 32971036

pii: S2352-3026(20)30291-X

doi: 10.1016/S2352-3026(20)30291-X

pii:

doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0

Cytarabine 04079A1RDZ

Dexamethasone 7S5I7G3JQL

obinutuzumab O43472U9X8

Banques de données

ClinicalTrials.gov

['NCT02896582']

Types de publication

Clinical Trial, Phase II Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

e798-e807