NcXHF

NEW TARGETED THERAPIES FOR iNHL
TABLE 2. Selected Molecular Pathways and Marketed Novel iNHL Therapies That Target Them
Phase(s) of
Pathway
Molecular
Target Agent Dosing Disease(s) FDA Indication(s)
Clinical
Trial Data
CD20 CD20 Ofatumumab 300 mg IV day 1 and 1,000 mg IV day CLL, FL CLL (first-line, relapsed) II, III
8 (cycle 1) and 1,000 mg IV day 1
(cycles 2-12) of 21-day cycles
Obinutuzumab 100 mg IV on day 1, 900 mg IV on CLL CLL (first-line) III
day 2, and 1,000 mg IV on days 8
and 15 (cycle 1) and 1,000 mg
on day 1 (cycles 2-6) of
21-day cycles
Ibritumomab tiuxetan 14.8 MBq/kg IV once, maximum 32 mCi FL, MZL iNHL or FL (relapsed); FL II, III
(first-line consolidation)
PI3K/Akt/mTOR PI3K Idelalisib 150 mg PO BID CLL, FL,
LPL, MZL
CLL/SLL, FL (relapsed) II, III
mTOR complex 1 Everolimus 10 mg PO QD CLL, MZL,
WM
Temsirolimus 25 mg IV every week CLL, FL,
WM
Renal cell carcinoma,
breast cancer
Renal cell carcinoma
BTK Ibrutinib 420 mg PO QD CLL/SLL MCL (relapsed), CLL (relapsed
and del[17p]), WM
560 mg PO QD FL
420 mg PO QD WM
Immunomodulation Cereblon Lenalidomide 25 mg PO QD, days 1-21 of 28-day
cycles
Proteasome
20S subunit
chymotryptic
site
Bortezomib 1.6 mg/m 2 IV on days 1, 8, 15, and 22
of 35-day cycles
Carfilzomib 20 mg/m 2 IV on days 1, 2, 8, and 9
(cycle 1), 36 mg/m 2 IV (cycle 2-6),
20 mg/m 2 on days 1 and 2
(maintenance) of 21-day cycles
Epigenetics Histone deacetylase Vorinostat 200 mg PO BID days 1-14
of 21-day cycles
DNA
methyltransferase
5-azacitidine 75 mg/m 2 SC on days
1-7 every 3 to 8
weeks
Decitabine 15 mg/m 2 IV on days 1-5
of a 28-day cycle
Immunotherapy PD-1 Nivolumab 3 mg/kg IV day 1 of
14-day cycles
FL, MZL,
SLL, WM
CLL, SLL, FL,
MZL, WM
CLL/SLL, FL,
WM
Multiple myeloma, MCL, MDS
Multiple myeloma, MCL
(relapsed)
Multiple myeloma (relapsed)
II
II
II, III
II
I, II, III
I, II
FL, MZL Cutaneous T cell lymphoma I, II
CLL MDS II
CLL MDS I
FL melanoma I, II
Abbreviations: IV, intravenous; CLL, chronic lymphocytic leukemia; FL, follicular lymphoma; PO, by mouth; SC, subcutaneous; Bq, becquerels; QD, once daily; BID, twice daily; MZL, marginal-zone
lymphoma; LPL, lymphoplasmacytic lymphoma; WM, Waldenström macroglobulinemia; SLL, small lymphocytic lymphoma; MCL, mantle cell lymphoma; MDS, myelodysplastic syndrome.
arm were older than age 75. Of those patients, 45% experienced
serious adverse events, and 5% of patients experienced
adverse events that led to death; similar rates were seen in the
comparator arms. 27 It is interesting to note that the CLL11
and COMPLEMENT-1 trials used different chlorambucil
regimens. A 65-kg person with body-surface area 1.8 m 2
would have received a substantially higher dose of chlorambucil
per cycle (126 vs. 65 mg) if enrolled in the
COMPLEMENT-1 trial, possibly accounting for the lower
response rate and PFS observed for the chlorambucil arm of
the CLL11 trial.
A cost-effectiveness study of obinutuzumab versus rituximab
in combination with chlorambucil found that obinutuzumab
increased QALYs by 0.56 compared with rituximab,
with an 89% probability that obinutuzumab was costeffective
at the $100,000 threshold. 28 The study was based on
Medicare reimbursements and wholesale acquisition costs
and was sponsored by Genentech, which markets obinutuzumab.
In contrast, the United Kingdom’s National Institute
for Health and Clinical Excellence (NICE) found that obinutuzumab/chlorambucil
versus rituximab/chlorambucil added
$45,000 per QALY in costs and $77,130 versus bendamustine/
rituximab in costs. NICE initially decided not to fund obinutuzumab,
fınding it inadequately cost effective. 29,30 NICE
revised its decision, funding obinutuzumab for the fırst-line
treatment of patients with CLL after a nondisclosed discounted
price was offered by the company. 31
Ofatumumab and obinutuzumab demonstrated substantial
activity in untreated older individuals, except for patients
with a 17p deletion (del[17p]). The caveats from these studies
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