LYMPHOMA in HIV PATIENTS. Silvia Montoto, St Bartholomew s Hospital, London, UK ESMO Preceptorship on Lymphoma

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1 LYMPHOMA in HIV PATIENTS Silvia Montoto, St Bartholomew s Hospital, London, UK ESMO Preceptorship on Lymphoma Lugano, 3-4 November 2017

2 Disclosures: Roche: honoraria Gilead: travel grant ESMO Preceptorship on Lymphoma Lugano, 3-4 November 2017

3 Lymphoma in HIV patients AIDS-related lymphoma (ARL) is an AIDS defining malignancy (ADM): -DLBCL (immunoblastic) -BL -PCNSL HL is a non-aids defining malignancy (NADM)

4 WHO 2008 classification

5 Incidence of lymphoma in HIV patients Increased incidence of NHL and HL in HIV+ patients NHL: x >100 in HIV+ HL: x in HIV+ Related to: CD4 count HAART Cause of death in HIV: 1/3 cancer (NHL most frequent)

6 HAART and incidence of NHL Engels et al, J Acquir Immune Defic Syndr, 2010

7 SMART study R Drug conservation Viral suppression DC* VS* HR P-value AIDS-defining malignancy Non AIDS-defining malignancy *Rate per 1000 py Silverberg et al, AIDS, 2007

8 Treatment of ARL : controversial points With/without HAART Infusional regimens vs conventional regimens With/without rituximab Salvage therapy

9 Treatment of ARL : controversial points With/without HAART Infusional regimens vs conventional regimens With/without rituximab Salvage therapy

10 Controversial points: with/without HAART Against: toxicity Haematological NRL In favour: efficacy But...no RCT

11 HAART vs no HAART in infusional regimens

12 Infusional regimens: toxicity DA-EPOCH No HAART CDE Pre-HAART HAART (43) (55) Febrile neutropenia 13% 10%* 6%* Dose reductions NS 48% 36% OI 8% 19% 8% Deaths 5 in remission (of 39 pts) 9% TRM 0 *grade 4 infection Sparano et al, JCO, 2004

13 So, HAART: with or without? Anti-retrovirals: NRTI NNRTI PI (other) HAART: combination of 2 NRTI + 1 NNRTI/ 1 PI Grade 3-4 infection Grade 4 neutropenia PI Non-PI p-value 48% 25% % 38% 0.05 Powles et al, AIDS, 2002 Bower et al, Blood, 2004

14 Outcome of HIV+ve on HAART vs no HAART DLBCL: CHOP vs CHOP-HAART HL: Chemo vs chemo-haart Vaccher et al, Cancer, 2001 Hentrich et al, Ann Oncol, 2006

15 Outcome depending on response to HAART Patients with HL treated with ABVD + HAART OS EFS Xicoy et al, Haematologica, 2007

16 Treatment of ARL: controversial points With/without HAART Infusional regimens vs conventional regimens With/without rituximab Salvage therapy

17 Infusional regimens in HIV-ve patients with DLBCL 524 patients Median follow-up: 5 yrs No diffs EFS or OS Presented at ASH 2016

18 Infusional regimens in HIV-lymphoma

19 Burkitt lymphoma vs DLBCL Pre-HAART HAART era M-BACOD/ CHOP like: 90%; CR: 35% Lim et al, JCO, 2005

20 Intensive chemotherapy in HIV-BL Oriol et al, Cancer, 2008

21 Intensive immunochemotherapy in HIV-BL: Burkimab N:118 pts 38 HIV+ve; CNS+ve: 14%; BM+ve: 26% DFS OS Ribera et al, Cancer, 2013

22 CODOX-M/IVAC: immunological recovery N:30 pts 73% high-risk (CNS involvement: 17%) HAART Montoto et al, AIDS, 2010

23 Treatment of ARL: controversial points With/without HAART Infusional regimens vs conventional regimens With/without rituximab Salvage therapy

24 CHOP vs CHOP-R in DLBCL Coiffier et al, N Engl J Med, 2002

25 Randomised N: % DLBCL CHOP-R x 6 + rituximab x 3 HAART, G-CSF CHOP-R vs CHOP CR/CRu rate: 58 vs 47% Disease progression: 8 vs 22% NS when CD4< 50 excl Kaplan et al, Blood, 2005

26 CHOP-R vs CHOP OS OS Kaplan et al, Blood, 2005

27 R-chemo vs chemo followed by R R-EPOCH vs EPOCH + 6 weekly doses of R Sparano et al, Blood, 2010

28 R-CHOP for DLBCL according to HIV status Coutinho et al, AIDS, 2010

29 Treatment of ARL: controversial points With/without HAART Infusional regimens vs conventional regimens With/without rituximab Salvage therapy

30 HDT in HIV-lymphoma: A retrospective case-matched comparative analysis of HIV+ vs HIV- patients Matching criteria Histology Status at transplantation IPI at diagnosis (for NHL patients) Ann Arbor stage at diagnosis Age at Auto-PBSCT Year of Auto-PBSCT Country of transplantation ASCT in HIV+ve Conditioning regimen: 92% BEAM Median CD34+: 4.9 G-CSF: 90% Díez-Martín et al, Blood, 2009

31 HDT in HIV-lymphoma: EBMT study Díez-Martín et al, Blood, 2009

32 Conclusion Treat HIV-lymphoma as lymphoma in HIV-ve BUT.

33 Work with HIV team Remember: Patients must be on HAART Avoid PI if possible Prophylactic antibiotics: Septrin (or pentamidine) Fluconazole Azythromycine Acyclovir

34 Thank you!