This study is a multicentric, single arm phase II trial to evaluate the efficacy of upfront obinutuzumab in mantle cell lymphoma patients treated by Cisplatinum-Cytarabine-Dexamethasone (DHAP) followed by autologous transplantation plus obinutuzumab maintenance then Molecular Residual Disease (MRD) driven maintenance

Patients will be recruited over 2 years. They must have a histologically proven diagnosis of mantle cell lymphoma, be aged from 18 to 65 years at the time of registration. Patients must be eligible for autologous transplant and not previously treated for their lymphoma at inclusion. Patients will receive 4 cycles of Obinutuzumab (GA101) and Cisplatinum-Cytarabine-Dexamethasone (GA-DHAP) every 21 days followed by Autologous Stem Cell Transplant (ASCT) using a GA101-Carmustine- Etoposide- Cytarabine- Melphalan (GA-BEAM) conditioning regimen plus a Obinutuzumab maintenance for 3 years then a Obinutuzumab maintenance on demand according to MRD status. Stem cells will be collected after cycle 3 and/or 4 of GA-DHAP.

Inclusion Criteria:

• Age ≥ 18 and age ≤ 65
• Histologically confirmed (according to the World Health Organization (WHO) classification) mantle cell lymphoma. The diagnosis has to be confirmed by phenotypic expression of CD5, CD20 and cyclin D1 or the t(11;14) translocation.
• Bone marrow aspiration performed at inclusion for MRD analyses
• Eligible for autologous stem cell transplant
• Previously untreated MCL
• Stage Ann Arbor II-IV in need of treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
• Life expectancy of more than 3 months
• Written informed consent
• Patient affiliated by any social security system

Exclusion Criteria:

• Severe cardiac disease: York Heart Association (NYHA) grade 3-4
• Impaired liver (ALanine Amino Transferase (ALAT)/ASparagin Amino Transferase (ASAT) ≥ 2.5 Upper Limit of Normal (ULN), bilirubin ≥ 1.5 ULN), renal (calculated creatinine clearance < 50 ml/min) or other organ function which will interfere with the treatment, if not related to lymphoma.
• History of chronic liver disease
• Hepatic veno-occlusive disease or sinusoidal obstruction syndrome
• Any of the following laboratory abnormalities, if not result of a BM infiltration:
• Absolute Neutrophils Count (ANC) <1,500 /mm3 (1.5 x 109/L)
• Platelet counts < 75,000/mm3 (75 x 109/L)
• Pregnancy/Nursing mothers
• Fertile men or women of childbearing potential unless:
• surgically sterile or ≥ 2 years after the onset of menopause
• willing to use a highly effective contraceptive method
• Patients with a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for ≥ 5 years prior to enrollment. Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible.
• Known seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) or other active infection uncontrolled by treatment.
• Viral infection with hepatitis B virus (HBV) defined as hepatitis B surface antigen (HBsAg) positive and/or Hepatitis B core antibody (anti-HBc) positive Note: Patients who are immune due to hepatitis B vaccination or natural infection (HBs Ag and anti-HBc negative, anti-HBs positive) are eligible. But the patients who are immune due to hepatitis B natural infection should consult liver disease experts before start of treatment and should be monitored and managed following local medical standards to prevent hepatitis reactivation
• Prior history of Progressive Multifocal Leukoencephalopathy (PML)
• Vaccination with a live vaccine a minimum of 28 days prior to inclusion (Prolonged B cell depletion)
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products
• Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.
• Person deprived of his/her liberty by a judicial or administrative decision
• Person hospitalized without consent
• Adult person under legal protection