NcXHF

MOREAU AND TOUZEAU
was able to induce a long TFI—or switch to a different treatment
regimen. Several factors influence this decision, including
drug availability in the specifıc country, patient age,
comorbidities, performance status, prior treatment, duration
of remission to the front-line regimen, and initial toxicities.
Although anti-MM treatments have proven effıcacious in
older patients with relapsed MM, their use is often associated
with substantial adverse effects that can affect treatment
choice. As such, older and frail patients usually are treated
with mild, low-dose regimens, typically thalidomide or bortezomib
combined with either melphalan/prednisone or cyclophosphamide/dexamethasone.
RELAPSE FOLLOWING INITIAL VMP
For patients previously exposed to a PI plus an alkylator, Rd
is the preferred option; it is approved, administered orally,
and easily manageable. As described above, the results of
ASPIRE (carfılzomib-Rd), POLLUX (daratumumab-Rd),
Eloquent-2 (elotuzumab-Rd), and TOURMALINE-MM1
(ixazomib-Rd) will soon modify the landscape of relapse
therapies. The choice of the particular regimen will depend
on safety, duration of response, OS rates, and cost. The population
of older patients is a very heterogeneous group, and
the studies described above generally have selected a fıt population
of patients, excluding frail patients, for whom QOL is
a major issue. In early 2015, only the results of the ASPIRE
study are available as a full manuscript and the PFS benefıt
was described in patients older than age 65 (HR 0.85).
RELAPSE FOLLOWING MPT
For patients treated up front with a combination of an alkylator
and thalidomide, several possibilities at the time of fırst
disease relapse exist. Rd is one possibility. A bortezomibbased
approach also is possible if patients did not experience
PN with thalidomide. Bortezomib/dexamethasone and bortezomib/liposomal
doxorubicin are two approved options.
The fırst is the preferred option because of convenience and
reduced toxicity. The triplet combination of RVD also was
tested in fırst disease relapse in a phase II study with good
results. 43 Similarly, the combination of bortezomib/dexamethasone
plus bendamustine has proven to be effective in
phase II studies. 44 Other triplet combinations currently undergoing
evaluation in phase III trials could present future
options, such as panobinostat plus bortezomib and dexamethasone
following the PANORAMA-1 results, or pomalidomide
plus VD.
RELAPSE FOLLOWING RD
The FIRST trial demonstrated the superiority of continuous
Rd over MPT in terms of ORR, PFS, and OS. When approved,
Rd will be a well-tolerated and effective oral frontline
regimen. At the time of progression on Rd, the addition
of a third drug will not be the preferred option. Instead, the
combination of a PI plus/minus alkylator (VD, VCD, or
VMP) could be the best choice. Depending on approval, the
triplet VD/panobinostat or VD/pomalidomide also could be
proposed.
TREATMENT OF RELAPSED AND REFRACTORY
MULTIPLE MYELOMA
Relapsed-and-refractory disease is defıned as a minimal response
to salvage therapy, as disease progressing during salvage
therapy, or disease progressing within 60 days of the last
therapy. These patients present a challenge because they are
likely to have a more aggressive disease and to be heavily pretreated,
thus having more pre-existing toxicities. Clinical trials
remain an important option for these patients.
Depending on the treatment to which a patient is refractory,
thalidomide, lenalidomide, or bortezomib (as single
agents or in combination) can be used for the subsequent line
of treatment. However, response rates tend to be lower than
in patients whose MM had relapsed because of the more advanced
state and aggressive nature of the disease and the development
of treatment resistance. Patients whose disease is
refractory to bortezomib and an IMiD have a median survival
of only 9 months with salvage treatment. 45 Therefore, there is
an unmet need for additional treatments for patients whose
disease is refractory to current regimens.
Two agents, pomalidomide and carfılzomib, recently have
been approved for use in patients with relapsed and refractory
MM, who have failed bortezomib- and lenalidomidebased
therapy.
POMALIDOMIDE
In the pivotal phase I/II study MM-002, the combination of
pomalidomide with low-dose dexamethasone (Pd) was
found to be more effıcacious than single-agent pomalidomide
in patients with relapsed and refractory MM (ORR, 34
and 15%, respectively). 46 In a randomized phase III study
(MM-003), Pd was compared to high-dose dexamethasone
in patients with primary refractory or relapsed and refractory
MM. At 10 months’ median follow-up, the PFS was substantially
longer in patients treated with Pd versus patients
treated with high-dose dexamethasone alone (median PFS,
4.0 vs. 1.9 months, respectively). 47 Comparable results were
seen in a subgroup analysis of patients who were dualrefractory
to bortezomib and lenalidomide (74% of patients
in the MM-003 trial) (median PFS, 3.7 months). 47 A substantial
improvement in OS was observed in the fınal analysis
(median OS, 12.7 vs. 8.1 months). 47
Pomalidomide in combination with low-dose dexamethasone
has been approved in Europe and the United States for
patients with relapsed and refractory MM whose disease has
progressed following at least two prior therapies, including
lenalidomide and bortezomib. As discussed previously, ongoing
studies are examining pomalidomide in combination
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