• Adult patients (≥18 years of age).

• Written informed consent must be obtained before any study-specific assessment is performed.

• Subjects with confirmed diagnosis of Mantle Cell Lymphoma according to the International Consensus Classification, (ICC) 2022\] or World Health Organization (WHO) Classification 2022. Classical, small-cell variants and marginal-zone variants can be included.

• Naïve patients for MCL management (no prior therapies, excluding diagnostic splenectomy)

• Asymptomatic patients

• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (0-1)

• Clinical stage I-IV according to the Ann Arbor classification with no symptoms attributable to MCL

• Patients with a leukemic non-nodal presentation with mainly bone marrow or peripheral blood involvement are eligible. Other asymptomatic clinical presentations are acceptable in case of low tumour burden, including MCL with lymph node enlargement ≤ 3 cm in the largest diameter and with low proliferation index (Ki67 \< 30%)

• The following laboratory values at screening:

‣ Neutrophil count ≥ 1×109/L, Haemoglobin level ≥ 100 g/L and platelet count ≥100×109/L

⁃ Transaminases (AST and ALT) ≤ 3 x ULN

⁃ Total bilirubin ≤1.5 x ULN unless bilirubin rise is due to Gilbert's disease

⁃ Calculated creatinine clearance ≥ 30 ml/min according to Cockcroft/Gault Formula (140 - age) × body weight (kg) × 0.85 (if female)/ serum creatinine (mg/dL) × 72

⁃ Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x ULN.

⁃ Stable disease without evidence of clinical progression for at least 3 months. Patients in prolonged observation may be included (over 3 months).

⁃ Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use highly effective contraception from the start of study treatment (See Appendix 4), during the treatment period and for at least 1 month following the last dose of pirtobrutinib and for 12 months following treatment with Rituximab.

⁃ Male patients must use highly effective contraception (if sexually active with a female of child-bearing potential) according to the recommendations provided by the Clinical Trial Facilitation and Coordination Group (CTFG), from start of study treatment, during the treatment period, and for at least 1 month following the last dose of pirtobrutinib and for 12 months following treatment with rituximab.

⁃ Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

⁃ Not included in other clinical trial or treated with an experimental drug unrelated to MCL within the past 2 years