LWBK1006-34 LWW-Govindan-Review November 24, 2011 11:25
Chapter 34•Plasma Cell Neoplasms 469when compared with TD (57% vs. 28%). Phase 2 trials have reported that
lenalidomide and dexamethasone are an appropriate induction regimen
pretransplant (Lacy et al. Blood [ASH Annual Abstracts] 2006;108[11]).
However, there are increasing data on the adverse impact of lenalidomide
on stem cell mobilization, and it is recommended that stem cells be col-
lected within the first 4 months of starting a lenalidomide-based regimen.
Unfortunately, we do not have any long-term follow-up from these trials
showing survival data. However, previous studies such as MRC VII and
IFM 90-06 on high-dose chemotherapy reported that patients achieving
CR after high-dose chemotherapy had longer progression-free survival
and OS compared with those with less than CR. Therefore, the VTD
regimen with the highest reported CR rate may be the most appropriate
induction regimen.Answer 34.3. The answer is A.
The optimal initial therapy for a young patient with multiple myeloma
is currently a subject of controversy. HDCT has been compared with
conventional chemotherapy in several randomized controlled trials. The
IFM 90-06 and MRCVII established HDCT as standard of care for
these patients. The introduction of novel drugs such as thalidomide,
lenalidomide, and bortezomib has improved the CR rate in patients
with myeloma and led several experts to question the continued role of
upfront HDCT for all patients with multiple myeloma. However, regi-
mens containing these novel drugs have not been directly compared with
HDCT in randomized trials, and most investigators think that these novel
agents should be incorporated with HDCT in the treatment paradigm.
Some investigators have suggested delaying the HDCT option for the
time of progression. This may be an appropriate strategy because a
randomized trial (Fermand JP. Blood. 1998;92[9]:3131–3136) showed
that HDCT at first progression resulted in OS comparable to patients
who underwent HDCT as initial therapy. However, there are no data
on delaying HDCT beyond first progression. Other investigators have
proposed a risk-stratified approach to HDCT for patients with multiple
myeloma. Deletion 13 by conventional cytogenetics was seen in approx-
imately 15% of patients with multiple myeloma and has been shown
to be an adverse prognostic factor. Trials with HDCT have reported a
median time to progression of 8 to 9 months in this population. How-
ever, deletion of chromosome 13 by FISH is detected in 40% to 50% of
patients. Individuals with deletion 13 detected by FISH in the absence
of deletion 13 by conventional cytogenetics do not seem to have the
same adverse impact. Therefore, we think that this patient with dele-
tion 13 detected by FISH alone should be offered HDCT as part of
her regimen. Bortezomib has been shown in several studies to negate
the adverse impact of deletion 13 detected by conventional cytogenet-
ics. However, because there are no randomized controlled trials com-
paring bortezomib-based combination regimen alone with HDCT, we
think that HDCT cannot be excluded from the treatment paradigm.
Melphalan-based regimen should be avoided in a patient eligible for
HDCT.