Low Grade Lymphomas Treatment approaches Parameswaran Venugopal MD

Low Grade Lymphomas: Treatment approaches Parameswaran Venugopal, MD Professor of Medicine Rush University Medical Center

SEER DATA 2015 2

SEER DATA 2015 3

Relative Incidence of NHL Subtypes Armitage and Weisenburger. J Clin Oncol. 1998; 16: 2780. Adapted from Jemal et al. CA Cancer J Clin. 2006; 56: 106. 4

Selected Indolent B-Cell Non-Hodgkin’s Lymphoma Subtypes Indolent Non-Hodgkin’s Lymphoma* Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal-zone lymphoma (6%) − Splenic MZL − Nodal MZL − Mucosa-associated lymphoid tissue Hairy cell leukemia (<1%) Waldenstrom macroglobulinemia (<1%) *% of all NHL. National Comprehensive Cancer Network. Practice Guidelines in Oncology. v. 2. 2006. At: http: //www. cancer. gov/ cancertopics/pdq/treatment/adult-non-hodgkins/Health. Professional/page 2. Accessed May 2006. Ansell and Armitage. Mayo Clin Proc. 2005; 80: 1087. 5

Low Grade Lymphoma · Indolent lymphoma accounts for 30%-40% of NHL cases – FL (22%), SLL (7%), MALT (8%), WM (uncommon) · Often asymptomatic · 85%-90% present in stage III or IV (Ann Arbor Staging) Winter et al. Hematology. 2004; 203. Armitage and Weisenburger. J Clin Oncol. 1998; 16: 2780. Adapted from Jemal et al. CA Cancer J Clin. 2005; 55: 10. Al-Tourah et al. ASCO, 2006. Abstract 7510. · Long median survival (~10 years) · Advanced disease rarely curable with conventional treatments · Transformation to aggressive lymphoma often occurs – 3% risk/year – 30% risk over 10 years 6

Follicular Lymphoma (FL) · Most common indolent NHL, accounts for ~22% of NHL in North America · Typically advanced stage at presentation · Often asymptomatic 7

FL: WHO/REAL Grading Grade 1 <5/hpf Grade 2 Grade 3 a 6 -15/hpf Grade 3 b >15/hpf Sheet 8

Diagnosis

Follicular Lymphoma: Diagnosis · B symptoms · Physical Examination · Laboratory studies: · Biopsy of Lymph Node · Bone Marrow Biopsy · CAT Scan · PET scan 10

Treatment

Follicular Lymphoma Common Management Approach After Staging Evaluation Localized Involved/Extended Field Radiation Advanced Low Tumor Burden High Tumor Burden Observation Therapy

Watch & Wait Radiotherapy Chemotherapy Monoclonal Antibodies Radioimmunotherapy Stem Cell Transplantation New Agents:

New Agents: Ibrutinib (Imbruvica) Idelalisib (Zydelig) Venetoclax (Venclexta) Obinutuzumab (Gazyva)

Rituximab as a Targeted Therapy in FL · Murine/human Ig. G 1 kappa monoclonal antibody Murine variable regions bind specifically to CD 20 on B cells · Binds to CD 20 antigen · Half-life (at 375 mg/m 2) ~76. 3 hours after 1 st infusion and 205. 8 hours after the 4 th infusion · Mechanism of action – CDC, ADCC, apoptosis, and ionizing radiation– induced cell death Human constant regions Human Ig. G 1 Fc domain works in synergy with human effector mechanisms CDC = complement-mediated cell death; ADCC = antibody-dependent cell cytotoxicity. 15

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Granules Antigen Fc region Antibody Fc receptor (Fcg. RIII) NK cell B cell Granules release perforins and granzymes; cytokines secreted (eg, IFNg) Lysis H 2 O, ions, granzymes NK = natural killer. Pores (perforin) 16

Radioimmunotherapy Ibritumomab Tositumomab Chelator Radionuclide Tiuxetan 17

Targeting of B Cell Receptor Niedermeier M, et al. Blood. 2009; 113(22): 5549 -5557.