New Options for High-risk CLL

Ibrutinib and idelalisib demonstrated efficacy in patients with CLL who harbor a chromosome 17p deletion—a feature that is notorious for difficult to treat disease, as chemoimmunotherapy typically elicits low response rates compared with wild-type 17p.13

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As a result, ibrutinib is recommended by the National Comprehensive Cancer Network as the preferred first-line agent for patients with a 17p deletion. Obinutuzumab plus chlorambucil may also be used as first-line therapy, and idelalisib with or without rituximab is recommended for relapsed or refractory disease.

Incorporating into Practice

The approval of obinutuzumab, ibrutinib, and idelalisib, as well as potential approvals of additional novel, targeted agents in the future provide clinicians with new and improved options for patients with CLL. However, how to best incorporate them into clinical practice remains a challenge.

For example, clinicians may be surprised at the extent of lymphocytosis that may occur in patients that receive one of these agents; however, lymphocytosis is generally asymptomatic and slowly normalizes.

“Many questions remain about their use including long-term efficacy, safety, and how and when to best incorporate these treatments into therapy,” wrote Dr. Sanford and colleagues.1

References

  1. Sanford DS, Wierda WG, Burger JA, et al. Three newly approved drugs for chronic lymphocytic leukemia: incorporating ibrutinib, idelalisib, and obinutuzumab into clinical practice. Clin Lymphoma Myeloma Leuk. 2015;15(7):385-391.
  2. Beers SA, Chan CH, French RR, et al. CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin Hematol. 2010;47(2):107-114.
  3. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-1110.
  4. Honigberg LA, Smith AM, Sirisawad M, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA. 2010;107(29):13075-13080.
  5. Cheng S, Ma J, Guo A, et al. BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. Leukemia. 2014;28(3):649-657.
  6. Chang BY, Francesco M, De Rooij MF, et al. Egress of CD19(þ)CD5(þ) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013;122(14):2412-2424.
  7. Byrd JC, Brown JR, O’Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-223.
  8. O’Brien S, Jones JA, Coutre S, et al. Efficacy and safety of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic leukemia with 17p deletion from the phase II RESONATE-17 trial. 56th ASH Annual Meeting and Exposition; San Francisco, CA. Abstract 327.
  9. Hoellenriegel J, Meadows SA, Sivina M, et al. The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood. 2011;118(13):3603-3612.
  10. Lannutti BJ, Meadows SA, Herman SE, et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011;117(2):591-594.
  11. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997-1007.
  12. Sharman JP, Coutre SE, Furman RR, et al. Second interim analysis of a phase 3 study of idelalisib (ZYDELIG) plus rituximab (R) for relapsed chronic lymphocytic leukemia (CLL): efficacy analysis of patient subpopulations with del(17p) and other adverse prognostic factors. 56th ASH Annual Meeting and Exposition; San Francisco, CA. Abstract 330.
  13. Zelenetz AD, Gordon LI, Wierda WG, et al. NCCN Clinical Practice Guidelines in Oncology. Non-Hodgkin Lymphoma. Version 2.2015. 2015. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf. Accessed July 21, 2015.

Topics:

Chronic Lymphocytic Leukemia Hematologic Cancers