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In a prospective, monocentric study including 22 patients completing 2 annual cycles of cladribine, B\u2010 and T\u2010cell receptor repertoires and relapse activity were assessed at baseline and after 24\u2009months. T\u2010cell clonality increased, driven by loss of low\u2010frequency, naive clonotypes, and re\u2010expansion of dominant CD8 memory clonotypes, particularly in clinically stable patients. In contrast, B\u2010cell receptor richness increased because of reconstruction by transitional and naive B cells with higher clonotype numbers observed in relapsing patients. Therefore, competing immune reconstitution following cladribine therapy could result in differential clinical responses. 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