1. AGGRESSIVE NON HODGKIN LYMPHOMA (NHL) EBMT 2015 CLINICAL CASE

2. CLINICAL CASE Mr L. N. 64 year old presented with a microcytic anemia: Hb: 11.3 g/100ml MGV: 79 fl And an iron deficiency: Serum iron: 5 μ mol/L Ferritin: 8.5 μ g/L

3. An ileo-coloscopy evidenced a submucosal tumor (30x40 mm) The biopsies revealed a lymphomatous polyposis expressing CD20 CLINICAL CASE

4. The thoraco-abdominopelvic CT scan highlighted: Mediastinal lymph nodes Bilateral axillary lymph nodes A splenomegaly (19 cm) A bulky retro-pancreatic mass (60x40 mm) A bulky colic mass (80x65 mm) with adjacent lymph nodes Inguinal lymph nodes. The trephine bone marrow biopsy did not evidenced lymphomatous invasion. CLINICAL CASE

5. Question 1: What is the clinical stage based on these informations? CLINICAL CASE

6. NHL - Initial Staging Evaluation of number and location of cancerous lymph nodes Stage IStage I : single Lymph Node region or single extra lymphatic organ/site (IE) Stage IIStage II: 2 or more LN regions on the same side of the diaphragm or single extra nodal site with adjacent nodes (IIE) Stage IIIStage III: nodal regions on both sides of the diaphragm Stage IV: disseminated involvement of one or more extralymphatic organs: bone marrow, liver, brain… Ann Arborr staging I –IV, B: presence of symptoms: unexplained fever, unexplained >10% weight loss, sweats

7. After review of the biopsy samples, the final conclusion is: Mantle Cell Lymphoma (MCL) CLINICAL CASE

9. Duration of Best Response (days) * Continuing response at last follow-up Pettengell et al. Lancet Oncol. 2012 Jul;13(7):696-706. Phase III PIX301: Tumor Response Duration

10. Phase III PIX301: PFS Pettengell et al. Lancet Oncol 2012;13:696. Time from randomization (months) 0 0.2 0.3 0.6 0.9 Progression-free survival probability 0.1 0.0 0.4 0.5 1.0 0.8 0.7 6121824 Pixantrone Comparator Pixantron e n = 70 Comparat or n = 70 Event (PD or death), n (%)58 (83%)64 (91%) Median PFS, months (95% CI) 5.3 (2.3, 6.2) 2.6 (1.9, 3.5) p = 0.005 HR = 0.60 (95% CI: 0.42, 0.86)

11. 0.5 PRECLINICAL CARDIOTOXICITY WITH EITHER DOXORUBICIN, MITOXANTRONE OR PIXANTRONE Cavalletti et al. Invest New Drugs 2007;25:187. Morphologic evaluation of cardiac lesions in mice following repeated treatment cycles of either doxorubicin, mitoxantrone or pixantrone Week 8Week 14Week 16Week 22 0.0 2.5 5.0 7.5 10.0 0.2 5.4 6.4 * *** 0.4 0.1 0.5 7.7 * *** 8.0 0.1 0.5 Pixantrone 27 mg/kg Doxorubicin 7.5 mg/kg Mitoxantrone 3 mg/kg Vehicle *p < 0.05 ***p < 0.001 Changes in mean total score (MTS) after 1 and 2 cycles of study drug