2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

effect on stem cell mobilization and does not cause DVT.
Since there are no data from randomized trials, the choice of
therapy is driven primarily by expert opinion, feasibility,
cost, and patient preference.
Based on cost and toxicity considerations, Rd or VCD are
probably the best options for this patient population at
present. After four cycles of therapy with Rd or VCD, stem
cells should be harvested, and patients can either undergo
frontline ASCT (preferred) or resume induction therapy,
delaying ASCT until first relapse.
Intermediate risk. In patients with standard risk, there
are no data from randomized trials that a bortezomibcontaining
regimen provides superior OS compared with Rd,
or vice versa. By contrast, so far only bortezomib-containing
regimens appear to be able overcome the poor prognosis
associated with the t4;14 translocation. 11 There are also
data that the best results in the t4;14 population come from
studies that used post-transplant bortezomib-based maintenance
therapy, and double ASCT.
High risk. Even regimens as aggressive as total therapy 3
(bortezomib-based induction therapy, tandem autologous
transplantation, and bortezomib-based maintenance therapy)
have not made any meaningful improvement in the
outcome of patients with high-risk disease. Some of these
Table 4. Major Treatment Regimens in Multiple Myeloma
Regimen Usual Dosing Schedule*
Melphalan-prednisone (7-d schedule) Melphalan 8–10 mg oral days 1–7
Prednisone 60 mg/d oral days 1–7
Repeated every 6 wk
Thalidomide-dexamethasone** Thalidomide 200 mg oral days 1–28
Dexamethasone 40 mg oral days 1, 8, 15, 22
Repeated every 4 wk
Lenalidomide-dexamethasone Lenalidomide 25 mg oral days 1–21 every 28 d
Dexamethasone 40 mg oral days 1, 8, 15, 22 every 28 d
Repeated every 4 wk
Bortezomib-dexamethasone** Bortezomib 1.3 mg/m 2 subcutaneous or intravenous days 1, 8, 15, 22
Dexamethasone 20 mg on day of and day after bortezomib (or 40 mg days 1, 8, 15, 22)
Repeated every 4 wk
Melphalan-prednisone-thalidomide Melphalan 0.25 mg/kg oral days 1–4 (use 0.20 mg/kg/d oral days 1–4 in patients over the age of 75)
Prednisone 2 mg/kg oral days 1–4
Thalidomide 100–200 mg oral days 1–28 (use 100 mg dose in patients �75)
Repeated every 6 wk
Bortezomib-melphalan-prednisone** Bortezomib 1.3 mg/m 2 subcutaneous or intravenous days 1, 8, 15, 22
Melphalan 9 mg/m 2 oral days 1–4
Prednisone 60 mg/m 2 oral days 1 to 4
Repeated every 35 d
Bortezomib-thalidomide-dexamethasone** Bortezomib 1.3 mg/m 2 subcutaneous or intravenous days 1, 8, 15, 22
Thalidomide 100–200 mg oral days 1–21
Dexamethasone 20 mg on day of and day after bortezomib (or 40 mg days 1, 8, 15, 22)
Repeated every 4 wk � 4 cycles as pre-transplant induction therapy
Bortezomib-cyclophosphamide-dexamethasone** (VCD) Cyclophosphamide 300 mg/m 2 orally on days 1, 8, 15 and 22
Bortezomib 1.3 mg/m 2 subcutaneous or intravenously on days 1, 8, 15, 22
Dexamethasone 40 mg orally on days on days 1, 8, 15, 22
Repeated every 4 wk†
Bortezomib-lenalidomide-dexamethasone** Bortezomib 1.3 mg/m 2 subcutaneous or intravenous days 1, 8, 15
Lenalidomide 25 mg oral days 1–14
Dexamethasone 20 mg on day of and day after bortezomib (or 40 mg days 1, 8, 15, 22)
Repeated every 3 wk‡
Reproduced from Rajkumar. 2
* All doses need to be adjusted for performance status, renal function, blood counts, and other toxicities.
** Doses of dexamethasone and/or bortezomib reduced based on subsequent data showing lower toxicity and similar efficacy with reduced doses.
† Omit day 22 dose if counts are low or when the regimen is used as maintenance therapy; when used as maintenance therapy for patients at high risk, delays can
be instituted between cycles.
‡ Omit day 15 dose if counts are low or when the regimen is used as maintenance therapy; when used as maintenance therapy for patients at high risk , lenalidomide
dose may be decreased to 10–15 mg per day, and delays can be instituted between cycles as done in total therapy protocols. 17,28
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S. VINCENT RAJKUMAR
patients may be content with the best quality of life possible,
given the grave prognosis, and choose a gentle approach
such as Rd. However, it would be reasonable to consider
expensive, albeit unproven, approaches such as VRD in this
patient population. It is not clear whether a full myeloablative
allogeneic transplantation may be of value, but some
patients are willing to take on the high risk of transplantrelated
mortality in exchange for a chance of long-term
survival.
Plasma cell leukemia or multiple extramedullary plasmacytomas.
Multiagent combination chemotherapy should be
considered for these patients as initial therapy since rapid
and reliable disease control is essential. VDT-PACE (bortezomib,
dexamethasone, thalidomide, cisplatin, doxorubicin,
cyclophosphamide, and etoposide) has been tested extensively
as part of the total therapy 3 trials and is a valuable
option. 17 Following two cycles of therapy, these patients
should be considered candidates for ASCT and subsequently
for maintenance therapy with a bortezomib-based regimen.
Options for Initial Treatment in Patients Not Eligible
for ASCT
In patients with newly diagnosed multiple myeloma who
are considered ineligible for ASCT because of age or other