Large-scale genome and exon sequencing studies of MM patients have revealed that only 10%–20% of LEN-resistant patients have mutations in CRBN axis-related genes, such as CRBN, IKZF1, and IRF4. 16,17 In addition, numerous genetic mutations in MAPK pathway genes and TP53 have been observed in LEN-resistant patients with MM16, yet only a limited number of these mutations contribute to LEN resistance.18 This evidence concerns the gene IKZF1 and Miyoshi myopathy.