Multi-Center Study of the Treatment and Characterization of Burkitt Lymphoma in Africa

1. Multi-Center Study of the Treatment and Characterization of Burkitt Lymphoma in Africa A Project of the INCTR African BL Strategy Group October 9, 2009

2. Overall Objectives • To characterize the presentation features of BL • To assess response, EFS, and OS in patients treated according to a uniform protocol • To assess the efficacy of a salvage regimen (Second Line Treatment)

3. Participating Institutions • Ocean Road Cancer Institute (ORCI), Tanzania • Kenyatta National Hospital (KNH), Kenya • ObafemiAwolowo University Teaching Hospitals Complex (OAUTHC), Nigeria • University College Hospital (UCH), Nigeria

4. Treatment Protocol • First Line Treatment (COM + IT therapy) for newly diagnosed, previously untreated patients • 3 cycles for low risk patients • 6 cycles for high risk patients • Second-Line Treatment (IFOS/MESNA, etoposide, ara-c + IT therapy) • Consists of 4 cycles of therapy • Patients who fail to respond to First-Line Treatment • Patients who relapse early (within 3 months) after completion of First-Line Treatment

5. First-Line Treatment

6. Second-Line Treatment

7. Patient Characteristics August 2004 – June 2008

8. Presentation Sites of Disease

9. Presentation Features: Comments • The majority of patients had multiple sites of disease • Difficult to state with accuracy how many patients had bone marrow involvement • Lack of needles • BM required hospitalizations at non-treating institutions • Difficult to state with accuracy how many patients had CSF/CNS involvement • In early years, cytocentrifuges not available • Technical problems remain (equipment)

10. Presentation Features: Comments • Patients with known BM and/or CNS involvement were eligible and included in the analysis • Patients who did not have a diagnostic BM or CSF exam prior to treatment were eligible and included in the analysis. • Patients who were HIV positive were also included.

11. Response to First-Line Treatment NE: 19 early deaths (tumor lysis, 10, infection, 5, disease, 4) and 5, lost to follow up.

12. Failures to First Line Treatment • Relapses: 43 • PR/NR: 45 • Treatment • Second Line treatment only: 40 • Repeat First Line treatment only: 11 • Both regimens: 11 • No treatment: 26

13. Summary of Indications for Use of Second Line

14. Response to Second Line Treatment

15. Second Line Treatment - Outcome • Survival ranges to 1 mo to 40 months • Estimated survival from the time of the start of Second-Line Treatment: • 46% at 6 months • 34% at 12 months

16. Protocol Deaths

17. Event Free and Overall Survival – All Patients • Event Free Survival • 54% at 12 months • 50% at 24 months • Events defined as: induction deaths, remission deaths, first relapse, and progressive disease • Overall Survival • 68% at 12 months • 61% at 24 months • 55% at 36 months

18. Survival – All Patients

19. Comparison of EFS and OS • EFS • There were no significant differences among institutions (p=0.12) • OS • There was significant variation among the centers with respect to survival (p=0.0016) • ORCI had significantly higher OS than the Nigerian centers (p=0.0001)

20. Comparison of OS

21. Comparison of OS • OS at 12, 24 and 36 months: • OAUTHC – 51%, 45%, 27% • UCH – 54%, 47%, 47% • KNH – 68%, 64%, 64% • ORCI – 78%, 69%, 67% (includes HIV+ cases) • ORCI – 80%, 71%, 69% (excludes HIV+ cases)

22. Goals • Prevent preventable deaths • Further improve patient follow up • Introduce Second Line treatment as part of First Line treatment for high risk patients • Improve pathology services • Introduction of immunohistochemistry • Central pathology review • On-going education and consultation with iPath

23. Summary • Support has been provided for: • Chemotherapy and supportive care drugs • Data manager salary support • Data monitoring is regularly performed • On-site • Close monitoring of data submitted to the central database • Patient accrual continues • 70 patients since June, 2008 • Study to begin in 4 new centers (Cameroon, Kenya (2 sites) and Uganda)

24. Summary - 2 • Relapse patients or partial responders to First-Line could be salvaged with Second Line Treatment or Repeat First Line Treatment (late relapse). • EFS and OS at 12 months is 54% and 68% respectively.

25. Conclusions • Significant improvements have been made in the management of patients with BL. • There is a need to further improve • Diagnosis capabilities • Pre-treatment evaluation (LDH, BM, CSF exams) • Data management • It is possible to cure patients, even in the setting of relapse or PR with this protocol.

26. Rapid Response 3.5 weeks Total cost of chemo ~ $200 INCTR African BL Treatment Project

27. Acknowledgements • UHC, Ibadan • Dr Yetunde Aken’Ova • Dr Biobele Brown • Mrs Tosin Olajedo • ORCI, Dar es Salaam • Dr Twalib Ngoma • Dr Jane Kaijage • Mr Seif Mkamba • KNH, Nairobi • Dr Jessie Githang’a • Dr Jamilla Rajab • Mr Oliver Oruko • OAUTHC, Ile-Ife • Dr Muheez Durosinmi • Dr OO Adeodu • Dr L Salawu • Mr Lukman Bashir • NCI, Bethesda, MD USA • Dr David Venzon INCTR Melissa Adde, Carol Falcon, Ian Magrath