NCCN Guidelines for Patients® | Chronic Lymphocytic Leukemia

39 NCCN Guidelines for Patients ® : Chronic Lymphocytic Leukemia, 2018 4 Treatment guide CLL without del(17p) or TP53 mutation Guide 4 lists treatment options for if the CLL responds but comes back (relapsed), or if the first treatment doesn’t work (refractory). This is treatment for relapsed or refractory disease for patients who are frail or sick, whether young or older. Before starting treatment, your doctor may want to test the cancer again. Features of cancer can change over time, so re-testing of the chromosomes in the cancer cells is advised. These tests include FISH, karyotype, and TP53 mutation status. The results are helpful in deciding on the next best treatment. If the features haven’t changed, ibrutinib alone and idelalisib with rituximab are preferred options. They are preferred due to good results measured in well- designed clinical trials. There are other drug options in Guide 4 that are listed in order of preference of NCCN experts. If you have a complete or partial response to treatment for refractory or relapsed disease, your doctor may consider a second maintenance therapy with lenalidomide or ofatumumab. Your doctor will test for MRD and decide on your next steps based on those results. MRD is when a very small amount of leukemia cells remains in your body after a course of treatment. With MRD, the amount of leukemia cells left is too small to be seen with a microscope. It is helpful to ask your doctor to explain any further treatment options you may have. Richter’s transformation is when CLL becomes a lymphoma such as DLBCL or Hodgkin lymphoma. CLL can also transform at a cellular level to another type of B-cell cancer called B-cell prolymphocytic leukemia. These cancer types can be aggressive and may follow a different treatment plan. See Guides 12 and 13. Guide 4. Treatments if prior treatment fails Frail and sick Treatment options (best options listed first) • Ibrutinib • Idelalisib + rituximab • Venetoclax ± rituximab • Idelalisib • Reduced-dose FCR ( f ludarabine, c yclophosphamide, r ituximab) • Reduced-dose PCR ( p entostatin, c yclophosphamide, r ituximab) • HDMP + rituximab • Rituximab + chlorambucil • Ofatumumab • Obinutuzumab • Lenalidomide ± rituximab • Alemtuzumab ± rituximab • Dose-dense rituximab • Bendamustine + rituximab ± ibrutinib • Bendamustine + rituximab ± idelalisib

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