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Safety and efficacy of an oncolytic viral strategy using bortezomib with ICE/R in relapsed/refractory HIV-positive lymphomas

Erin G. Reid, David Looney, Frank Maldarelli, Ariela Noy, David Henry, David Aboulafia, Juan Carlos Ramos, Joseph Sparano, Richard F. Ambinder, Jeannette Lee, Ethel Cesarman, Sara Yahyaei, Ronald Mitsuyasu and William Wachsman for the AIDS Malignancy Consortium

Data supplements

Article Figures & Data

Figures

  • Figure 1.

    PBMC KSHV viral load change in patients with PEL. More than 1 log-increase occurred in PBMC KSHV viral load after bortezomib administration in the 2 patients with KSHV-positive PEL, both of whom achieved a response to protocol therapy (1 CR, 1 PR).

  • Figure 2.

    Plasma HIV viral load change in patients not receiving ART. Three patients not already undergoing ART at enrollment did not start ART until completion of protocol therapy. Plasma HIV viral load data during cycle 1 are plotted here for each patient, demonstrating a downward trend as hypothesized in 2 of the 3 patients throughout the first week of protocol therapy, during which patients received single-agent bortezomib.

  • Figure 3.

    APOBEC3G levels increased in 75% of evaluable patients after bortezomib administration. APOBEC3G was measured by using western blot on PBMC from 12 patients. (A) PBMCs from both baseline and day 8 were lysed, and proteins were separated by using sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Gel lanes were reordered in the figure to group according to bortezomib dose level. (B) APOBEC3G level was quantified by using ImageJ software (National Institutes of Health, Bethesda, MD), and the results are presented as a fold change in the level of APOBEC3G normalized to actin.

Tables

  • Table 1.

    Demographic and baseline characteristics

    Characteristicn%
    Sex
     Male2091
     Female29
    Race
     White1568
     African American627
     Other15
    Ethnicity
     Hispanic523
     Non-Hispanic1777
    Age, y
     Median48
     Range34-66
    CDC risk group
     Homosexual/bisexual contact1568
     Heterosexual contact523
     Homosexual and heterosexual contact15
     IV drug use15
    Receiving ART at enrollment2087
    Absolute CD4 count, μL
     Median315
     Minimum-maximum45-773
    HIV viral load, copies/mL
     MedianUndetectable
     Minimum-maximumUndetectable to 241 490
    Ann Arbor stage
     I314
     II314
     IIE15
     III314
     IV1255
    Lymphoma diagnosis
     DLBCL1568
     PEL29
     Plasmablastic lymphoma314
     Hodgkin lymphoma29
    • CDC, Centers for Disease Control and Prevention.

  • Table 2.

    Adverse events assessed as at least possibly related to bortezomib

    CTC system organ classCTC adverse event termCTC adverse event gradeAll
    1234
    NNNNN
    Blood and lymphatic system disordersAnemia059014
    Febrile neutropenia00202
    Eye disordersBlurred vision10001
    Gastrointestinal disordersAbdominal pain00101
    Constipation11002
    Diarrhea11204
    Mucositis oral11002
    Nausea40004
    Vomiting30003
    General disorders and administration site conditionsFatigue40105
    Fever10001
    Injection site reaction10001
    Pain10001
    Infections and infestationsMucosal infection10001
    InvestigationsAlkaline phosphatase increase20002
    Lymphocyte count decreased10326
    Neutrophil count decreased022812
    Platelet count decreased014712
    White blood cell decreased021710
    Metabolism and nutrition disordersAnorexia11002
    Hypokalemia00101
    Hypomagnesemia10001
    Hyponatremia10001
    Hypophosphatemia01405
    Nervous system disordersDysgeusia10001
    Headache21003
    Neuralgia10102
    Paresthesia10001
    Peripheral sensory neuropathy20002
    Seizure00101
    Syncope00101
    Psychiatric disordersInsomnia01001
    Respiratory disordersCough10001
    Skin and subcutaneous tissue disordersAlopecia01001
    Vascular disordersHypotension00202
    • CTC, Common Toxicity Criteria.

  • Table 3.

    Patient-specific disease characteristics, treatment, and outcome

    Lymphoma typeAnn Arbor stageLymphoma EBV/KSHV statusBaseline CD4, cells/μLBaseline HIV, copies/mLBortezomib dose cohort, mg/m2Total no. of cycles completedBest responseDuration of response, wkPostprotocol lymphoma therapySurvival, wk
    DLBCLIVEBV positive294241 4900.76CR>68.5None>68
    DLBCLIVEBV positive7785 1220.72PD*NARadiation38
    DLBCLIVEBV positive4021700.74CR*>55None>55
    PlasmablasticIVEBV positive1691260.72SDNAAHSCT29
    PELIVEBV and KSHV positive570480.74PR15AHSCT24
    DLBCLIIEBV positive2610.72PDNARadiation26
    DLBCLIVEBV positive336Undetectable1.03PR*4Not reported19
    Not reported1.00NANANANA
    DLBCLIVEBV positive4880001.0<2NENENot reported9
    DLBCLIVEBV positive45891.0<1NENENone3
    HodgkinIIIEBV positive283<4001.02CR*>55AHSCT>55
    PlasmablasticIEBV positive476<201.04CR*>59AHSCT>59
    DLBCLIIEEBV positive435Undetectable1.03PR>40AHSCT>40
    DLBCLIVEBV negative3344.41.03PR*6Not reported>13
    HodgkinIIIEBV positive3560.71.33PR>60AHSCT>60
    PELIIEBV and KSHV positive4501.21.36CR*>58None>58
    DLBCLIIIEBV negative2370.41.33PR>55AHSCT>55
    PlasmablasticIEBV positive2940.451.54PR5Not reported>14
    DLBCLIVEBV negative29624 8171.53CR*>43None52
    DLBCLIVEBV positive401241.55PR*>65Radiation>65
    DLBCLIUnknown2414.21.53PR2Not reported>12
    DLBCLIIUnknown7731.31.54PR*>52R2-GemOx + AHSCT>52
    DLBCLIVEBV negative339Undetectable1.53CR*6AHSCT16
    • NA, not applicable; NE, not evaluable; PD, progressive disease; R2-GemOx, lenalidomide, rituximab, gemcitabine, and oxaliplatin; SD, stable disease.

    • * PET imaging used in response assessment.

    • In continued CR at time of death attributed to complications of AHSCT.