Page 456 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

440 PART 6 ■ Neoplastic Disorders

BOX 22.4

Emerging Therapies: Novel Combination Therapies in Relapsed Patients

IMMUNOMODULATORY AGENTS (IMIDS) o histone e cetyl se inhibition while ini izing

1. Len li o i e is secon -gener tion IMiD with gre ter toxicity.

potency n less toxicity th n th li o i e.

2. Po li o i e is thir -gener tion IMiD th t sh res OTHER NEW TARGETS

nu ber o benef ci l ph r cologic properties with 1. KSP Inhibitors

len li o i e. ARRY-520 inhibits the spin le or tion uring itosis

th t results in cell e th, poptosis.

PROTEASOME INHIBITORS (PIS) 2. AK Inhibitors

1. Bortezo ib is the f rst to h ve single- gent ctivity n A uresertib is selective or l AK kin se inhibitor with

co bines well with ny other gents. ntitu or ctivity in soli tu ors.

2. C rf lzo ib is secon -gener tion epoxyketone, which 3. Selective Inhibitor o Nucle r Export

in uces irreversible prote so e inhibition n co bines Selinexor, lso known s KP -330, is new or l novel

well with other gents. gent. It is the f rst rug in new cl ss o gents known

s Selective Inhibitor o Nucle r Export (SINE™ ) co -

HISTONE DEACETYLASE INHIBITORS (HDAC) poun s. Selinexor works by inhibiting XPO1, protein

1. Vorinost t is p n- e cetyl se inhibitor th t c n be oun in the nucleus o c ncer cells, which ctiv tes

co bine with bortezo ib. tu or suppressors by ret ining the in the nucleus o

2. P nobinost t is the f rst FDA- pprove HDACi or c ncer cells. T is results in poptosis o c ncer cells,

yelo p tients who h ve receive t le st two prior while l rgely sp ring nor l cells. Selinexor lso re uces

st n r ther pies, inclu ing bortezo ib n n i u- the levels o onco-proteins such s c- yc n bcl-2, th t

no o ul tory gents. re uces the growth o c ncer cells.

3. Rocilinost t (ACY-1215) is selective HDAC-6 inhibitor Re erence: Loni S, Nook AK. Novel co bin tion ppro ches or

evelope in n tte pt to preserve the clinic l e c cy yelo , Hematology Am Soc Hematol Educ Program, 2015, 286–292.

Regul tory cell ( regs ) re CD4+ cells th t strongly WALDENSTRÖM PRIMARY

inhibit ntitu or i une responses in yelo p tients.
MACROGLOBULINEMIA

(LYMPHOPLASMACYTIC LYMPHOMA)

Therapeutic Vaccinations
Epidemiology

Den ritic cell (DC) v ccines re APCs th t c n sti ul te

vigorous -cell i une responses. Novel ppro ches o T e con ition o WM h s n ge-specif c inci ence. It is

co bining DC v ccine n PD-1 ntibo y or post utolo- ost co only oun in ol er en; the e i n ge o

gous tr nspl nt re un ergoing clinic l tri ls. onset v ries between 63 n 68 ye rs o ge. Onset is usu-

Pepti e v ccines re represente by PVX-410, which lly insi ious. T e inci ence o WM is higher ong whites.

is co pose o tetr pepti e ro three unique regions Ninety percent o p tients with WM h ve MYD88 L265P

o yelo - ssoci te ntigen XBP, CD138, n CS1. ut tions.

he go l o this v ccine is to in uce i unity g inst

yelo cells by selectively sti ul ting tu or- ssoci- Pathophysiology

te ntigen-speci ic cytotoxic ly phocytes (PVX-410

lone n in co bin tion with len li o i e) th t re WM is B-cell neopl s ch r cterize by ly phopl s o-

being ev lu te or the tre t ent o s ol ering yelo . proli er tive isor er with inf ltr tion o the bone rrow
n onoclon l i unoglobulin M (IgM) protein. T is

lign nt ly phocyte–pl s cell proli er tive isor er is
Prognosis
ssoci te with the pro uction o bnor lly l rge ounts

T is isor er runs progressive course, n ost p tients o g globulin o the 19S or IgM type. T e b sic bnor-

ie in 1 to 3 ye rs. T e jor c uses o e th re in ection lity in this croglobuline i is uncontrolle proli er -

n ren l insu ciency. tion o ly phocyte n pl s cells.