2. Also known as lymphoplasmacytic lymphoma A rare type of non-Hodgkin lymphoma WM affects lymphoplasmacytic (LPL) Cells B-Cells LPL Cells Plasma Cells Abs In WM – Abnormal LPL cells build up In bone marrow -crowding out healthy blood cells In lymph nodes, spleen, and other organs Abnormal LPL cells IgM Ab Second level

3. “Macroglobulinemia” means IgM in blood, increasing the thickness of the blood -hyperviscosity WM spreads to blood and bone marrow May spread to lymph nodes, liver, spleen, stomach, intestines, and lungs Develops slowly- may not need treatment for months or years

4. Watchful waiting Plasmapheresis- Plasma Exchange Reduces thickness of blood A blood cell separator is used Blood is removed through vein Red and white blood cells are separated from plasma Blood cells are mixed with a plasma substitute Blood is returned to body Second level

5. Chemotherapy Systemic therapy IV, tablet or under the skin Prevents cancer cells from growing and dividing Commonly used chlorambucil (Leukeran ®) fludarabine (Fludara ®) cladribine (Leustat ®) cyclophosphamide bendamustine (Levact ®) Combination Chemotherapy Second level

6. Corticosteroids Stem Cell or Bone Marrow Transplantation Hematopoietic stem cells- from patient’s own blood or bone marrow Serious risks and sporadic effectiveness Cancerous bone marrow hematopoietic stem cells

7. Rituximab (Rituxan, Mabthera) Monoclonal antibody that binds to an antigen (CD20) specific to the malignant cell Kills cancer cells or makes susceptible to chemotherapy Ibrutinib (Imbruvica)-FDA approved An inhibitor of BTK (kinase) Shuts down signaling cascade, inhibiting transcription and growth in malignant B-cells

8. Bortezomib (Velcade ®) Proteasome inhibitor Proteasomes break down proteins in normal and cancerous cells, and Velcade prevents this normal process Alemtuzumab (Campath) Monoclonal antibody that targets CD52- an antigen on tumor cell surface- destroying tumor cells Bendamustine (Treanda) Chemotherapy Used when first diagnosed or upon recurrence

9. Idelalisib Kinase inhibitor Inhibits P13 kinase, inhibiting tumor cell growth Everolimus (Afinitor) and Temsirolimus (Torisel) mTOR inhibitors Inhibit cell cycle and proliferation of tumor cells Panobinostat Non-selective HDAC inhibitor Inhibits histone deacetylase enzymes, causing apoptosis

10. Combinations of several chemotherapy drugs, targeted therapies and/or corticosteroids Currently used Monoclonal antibodies (Rituximab) plus chemotherapy Chemotherapy drugs fludarabine and cyclophosphamide Being Studied Bortezomib (proteasome inhibitor), dexamethasone (corticosteroid), and rituximab (monoclonal antibody)