Chronic lymphocytic leukemia (CLL) Tanya Siddiqi, MD Assistant Professor City of Hope National Medical Center Duarte, CA How the Experts Treat Hematologic Malignancies Las Vegas, 3-11-16

Disclosures • Speaker for Pharmacyclics/Janssen (ibrutinib) • Speaker for Seattle Genetics (brentuximab vedotin) • I will be mentioning off label use for some novel treatments currently being investigated

Agenda

• • • • •

Overview Indications for treatment Treatment options Novel therapies COH treatment algorithm – Frontline – Relapsed/refractory

• Ongoing trials

CLL overview • Chronic lymphocytic leukemia (CLL) is a low grade leukemic lymphocytic lymphoma; small lymphocytic lymphoma (SLL) is a nodal form of the same disease

• CLL/SLL is the most common hematological malignancy in the Western world; incidence is ~5/100,000 persons per year in the US • Median age at diagnosis ~72 years

Muller-Hermlink HK, et al. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours in Haematopoietic and Lymphoid Tissues. Lyon, France. IARC press, 2001: 195-6.

Epidemiology

• Male predominance • Higher in Caucasians • ~10% patients with a family history of some lymphoma

• Exact etiology is unknown

Initial Presentation of Patients With CLL

• Clinical course is variable • Many are asymptomatic at diagnosis – Referred when white blood cell and/or lymphocyte counts are elevated on routine tests

• 10% have B symptoms

Nabhan C et al. JAMA. 2014;312:2265-2276. Furman RR. Hematology Am Soc Hematol Educ Program. 2010:77-81.

Initial Workup of Patients With CLL • Flow cytometry – Peripheral blood monoclonal B lymphocytes ≥5 x 109/L – Immunophenotyping: k/l dim, CD5+, CD19+, CD20 dim, CD23+, CD10-, cyclin D1– FISH t(11;14) – Rule out masquerading lymphomas

• H&P, performance status: note any B-symptoms • CBC, differential, CMP, LDH • Imaging studies and bone marrow/LN biopsies are not routinely required NCCN Guidelines® for Non-Hodgkin’s Lymphomas Version 1.2016.

Monoclonal B-lymphocytosis (MBL) • Presence of monoclonal lymphocytosis but with 5000/mcL

I-II: • Lymphadenopathy and/or hepatosplenomegaly Intermediate III-IV: High

• Anemia and/or thrombocytopenia • Hb