Human immunodeficiency virus-associated Lymphomas: EHA-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Abstract

This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing HIV-associated lymphomas.The guideline covers clinical, imaging and pathological diagnosis; staging and risk assessment; treatment and follow-up.The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe.Recommendations are based on available scientific data and the authors' collective expert opinion.

Figure 1

Management of HIV–DLBCL. Purple: algorithm title; blue: systemic anticancer therapy or their combination; turquoise: non‐systemic anticancer therapies or combination of treatment modalities; white: other aspects of management and non‐treatment aspects. ASCT, autologous stem‐cell transplantation; CMR, complete metabolic response; CVD, cardiovascular disease; DA‐R‐EPOCH, dose‐adjusted rituximab–etoposide–prednisone–vincristine–cyclophosphamide–doxorubicin; HIV–DLBCL, human immunodeficiency virus‐associated diffuse large B‐cell lymphoma; ICT, immunochemotherapy; PR, partial response; R‐CHOP, rituximab–cyclophosphamide–doxorubicin–vincristine–prednisone; R‐DHAP, rituximab–dexamethasone–cytarabine–cisplatin; R‐ESHAP, rituximab–etoposide–methylprednisolone–cytarabine–cisplatin; R‐GDP, rituximab–gemcitabine–dexamethasone–cisplatin; R‐ICE, rituximab–ifosfamide–carboplatin–etoposide; SD, stable disease.

Figure 2

First‐line management of HIV–BL. Purple: algorithm title; blue: systemic anticancer therapy or their combination; white: other aspects of management and non‐treatment aspects; dashed lines: optional therapy. Ara‐C, cytarabine; BL, Burkitt lymphoma; CALGB, Cancer and Leukemia Group B; CNS, central nervous system; CSF, cerebrospinal fluid; CSF+, cerebrospinal fluid positive; CT, computed tomography; DA‐R‐EPOCH, dose‐adjusted rituximab–etoposide–prednisone–vincristine–cyclophosphamide–doxorubicin; ECOG, Eastern Cooperative Oncology Group; EMA, European Medicines Agency; EoT, end of treatment; FDA, Food and Drug Administration; FDG, [¹⁸F]2‐fluoro‐2‐deoxy‐D‐glucose; GMALL‐B‐ALL, German Multicentre Study Group for Adult Acute Lymphoblastic Leukaemia B‐cell acute lymphoblastic leukaemia; HIV–BL, human immunodeficiency virus‐associated Burkitt lymphoma; i, interim; IPI, International Prognostic Index; IT, intrathecal; LDH, lactate dehydrogenase; LMB, lymphomes malins B; MTX, methotrexate; PET, positron emission tomography; PS, performance status; R‐CHOP, rituximab–cyclophosphamide–doxorubicin–vincristine–prednisone; R‐CODOX‐M, rituximab–cyclophosphamide–vincristine–doxorubicin–methotrexate; R‐IVAC, rituximab–ifosfamide–etoposide–cytarabine; ULN, upper limit of normal. ^aRituximab is not EMA or FDA‐approved for the treatment of BL. ^bBL‐IPI factors are age ≥40 years, ECOG PS 2‐4, LDH >3 × ULN and CNS involvement, as per Olszewski et al. ^cRisk definition as per Roschewski et al. ^dOr equivalent regimens. Rituximab‐containing regimens such as LMB, GMALL‐B‐ALL and CALGB protocols are valid alternatives to R‐CODOX‐M or R‐IVAC. ^eR‐CODOX‐M or R‐IVAC (or equivalent regimens) are preferred for patients with high‐risk BL‐IPI and for those with CNS disease at diagnosis. ^fDA‐R‐EPOCH is an alternative for less fit patients or those aged >60 years. ^gConsider R‐CHOP plus immunotherapies for elderly and/or unfit patients with the aim of escalating if fitness improves. ^hDA‐R‐EPOCH may be preferred for patients with low‐ or intermediate‐risk BL‐IPI, especially those aged >60 years.

Figure 3

First‐line management of HIV–PBL. Purple: algorithm title; blue: systemic anticancer therapy or their combination; turquoise: non‐systemic anticancer therapies or combination of treatment modalities; white: other aspects of management and non‐treatment aspects; dashed lines: optional therapy. ASCT, autologous stem‐cell transplantation; CHOP, cyclophosphamide–doxorubicin–vincristine–prednisone; CODOX‐M, rituximab–cyclophosphamide–vincristine–doxorubicin–methotrexate; EMA, European Medicines Agency; EPOCH, etoposide–prednisone–vincristine–cyclophosphamide–doxorubicin; FDA, Food and Drug Administration; HIV–PBL, human immunodeficiency virus‐associated plasmablastic lymphoma; hyper‐CVAD, hyperfractionated cyclophosphamide–vincristine–doxorubicin–dexamethasone; IVAC, ifosfamide–etoposide–cytarabine; PBL, plasmablastic lymphoma; RT, radiotherapy. ^aNot EMA or FDA approved for the treatment of PBL.

Figure 4

Management of r/r HIV–PBL. Purple: algorithm title; blue: systemic anticancer therapy or their combination; turquoise: non‐systemic anticancer therapies or combination of treatment modalities; white: other management and non‐treatment aspects. Allo‐SCT, allogeneic stem‐cell transplantation; ASCT, autologous stem‐cell transplantation; BV, brentuximab vedotin; CD, cluster of differentiation; DHAP, dexamethasone–cytarabine–cisplatin; EMA, European Medicines Agency; ESHAP, etoposide–methylprednisolone–cytarabine–cisplatin; FDA, Food and Drug Administration; HIV–PBL, human immunodeficiency virus‐associated plasmablastic lymphoma; ICE, ifosfamide–carboplatin–etoposide; PBL, plasmablastic lymphoma; r/r, relapsed or refractory. ^aNot EMA or FDA approved for the treatment of PBL.

Figure 5

First‐line management of HIV–PEL. Purple: algorithm title; blue: systemic anticancer therapy or their combination; turquoise: non‐systemic anticancer therapies or combination of treatment modalities; white: other management and non‐treatment aspects; dashed lines: optional therapy. ASCT, autologous stem‐cell transplantation; CD, cluster of differentiation; CHOP, cyclophosphamide–doxorubicin–vincristine–prednisone; DA, dose‐adjusted; EMA, European Medicines Agency; EPOCH, etoposide–prednisone–vincristine–cyclophosphamide–doxorubicin; FDA, Food and Drug Administration; HDCT, high‐dose chemotherapy; HIV, human immunodeficiency virus; HIV–PEL, human immunodeficiency virus‐associated primary effusion lymphoma; PEL, primary effusion lymphoma. ^aNot EMA or FDA approved for the treatment of PEL.

Figure 6

Management of r/r HIV–PEL. Purple: algorithm title; blue: systemic anticancer therapy or their combination; turquoise: non‐systemic anticancer therapies or combination of treatment modalities; white: other aspects of management and non‐treatment aspects. Allo‐SCT, allogeneic stem‐cell transplantation; ASCT, autologous stem‐cell transplantation; BV, brentuximab vedotin; CAR‐T, chimeric antigen receptor T‐cell therapy; CD, cluster of differentiation; DHAP, dexamethasone–cytarabine–cisplatin; EMA, European Medicines Agency; ESHAP, etoposide–methylprednisolone–cytarabine–cisplatin; FDA, Food and Drug Administration; GDP, gemcitabine–dexamethasone–cisplatin; HDCT, high‐dose chemotherapy; HIV–PEL, human immunodeficiency virus‐associated primary effusion lymphoma; ICE, ifosfamide–carboplatin–etoposide; PEL, primary effusion lymphoma; r/r, relapsed or refractory. ^aNot EMA or FDA approved for the treatment of PEL.

Figure 7

First‐line management of HIV–PCNSL. Purple: algorithm title; turquoise: non‐systemic anticancer therapies or combination of treatment modalities; white: other aspects of management and non‐treatment aspects. ART, combination antiretroviral therapy; ASCT, autologous stem‐cell transplantation; EMA, European Medicines Agency; FDA, Food and Drug Administration; HD‐MTX, high‐dose methotrexate; HIV, human immunodeficiency virus; HIV–PCNSL, human immunodeficiency virus‐associated primary central nervous system lymphoma; MATRix, rituximab–methotrexate–cytarabine–thiotepa; PCNSL, primary central nervous system lymphoma. ^aRituximab is not EMA or FDA approved for the treatment of PCNSL. ^bWhen the lymphoma resembles that of the immunocompetent host.

Figure 8

Management of HIV–HL. Purple: algorithm title; blue: systemic anticancer therapy or their combination; turquoise: non‐systemic anticancer therapies or combination of treatment modalities; white: other aspects of management and non‐treatment aspects. ABVD, doxorubicin–bleomycin–vinblastine–dacarbazine; ASCT, autologous stem‐cell transplantation; AVD, doxorubicin–vinblastine–dacarbazine; BEACOPP, bleomycin–etoposide–doxorubicin–cyclophosphamide–vincristine–procarbazine–prednisone; BV, brentuximab vedotin; CT, computed tomography; FDG, [¹⁸F]2‐fluoro‐2‐deoxy‐D‐glucose; FDG–PET–CT+, positive findings on FDG–PET–CT; HDCT, high‐dose chemotherapy; HIV–HL, human immunodeficiency virus‐associated Hodgkin lymphoma; ID, individual decision; IFRT, involved‐field radiotherapy; ISRT, involved‐site radiotherapy; PET, positron emission tomography; RT, radiotherapy. ^aNo data in HIV–HL.

Figure 9

First‐line management of HHV‐8–MCD. Purple: algorithm title; blue: systemic anticancer therapy or their combination; turquoise: non‐systemic anticancer therapies or combination of treatment modalities; white: other management and non‐treatment aspects. ART, combination antiretroviral therapy; CD, cluster of differentiation; EMA, European Medicines Agency; FDA, Food and Drug Administration; HHV‐8–MCD, human herpesvirus 8‐associated multicentric Castleman disease; i.v., intravenous; KS, Kaposi sarcoma; MCD, multicentric Castleman disease. ^aEtoposide can be added to the first cycle to avoid a possible flare. ^bNot EMA or FDA approved for the treatment of MCD. Rituximab should be used with caution in patients with a CD4 count <50 cells/µL and/or delayed after a few courses of etoposide, but may be considered as it is associated with improved outcome in MCD and reduces the risk of lymphoma development. ^cThe number of liposomal doxorubicin cycles depends on the burden of KS disease, but the minimum number is four. ^dEtoposide can be administered orally or by i.v. injection; the i.v. route optimises bioavailability.