At present, NCCN guidelines recommend the following agents as maintenance therapy in MM: interferon alfa (category 2B);
corticosteroids (category 2B); thalidomide (category 1) with or without prednisone (category 2B); and lenalidomide (category 2A).3
In addition, bortezomib is currently under investigation in the maintenance setting, but the NCCN panel has deemed current
data inadequate to make a recommendation.3
...the criteria used to determine whether maintenance therapy is an appropriate strategy in a patient with MM.
Interferon Alfa as Maintenance Therapy
Interferon alfa as maintenance therapy in MM has been investigated in several clinical trials,
but the findings have been inconsistent.9,13
Data from two meta-analyses showed that interferon alfa produced a statistically significant (albeit small) survival advantage
when used after conventional therapy.9 In one meta-analysis, based on 1615 patients with MM in 13 trials, interferon alfa maintenance
therapy, compared with no treatment, prolonged relapse-free and overall survival by 4.4 and 7.0 months, respectively (P<.01).13
In the second meta-analysis, based on 1543 patients with MM in 12 trials, response duration was better with interferon alfa maintenance
therapy (27% vs 19%, respectively, at 3 years; log rank P<.00001); furthermore, interferon alfa prolonged median time to progression
by approximately 6 months.14
A clinical trial in 101 patients with MM who had responded to conventional induction chemotherapy showed that maintenance therapy with interferon alfa,
compared with no treatment, significantly improved duration of response (26 vs 14 months, respectively; P=.0002)15; median overall survival
in the two groups was 52 vs 39 months, respectively (P=.0526).15 In a prospective randomized trial conducted by the Spanish Society of Hematology
in 92 patients with MM who had responded to VCMP/VBAP (vincristine, cyclophosphamide, melphalan, prednisone/vincristine, carmustine,
doxorubicin, prednisone) chemotherapy, median duration of response from time of randomization until relapse was 13 months in the interferon
alfa group and 7.7 months in the no-treatment group (P=.042)16; median survival from time of randomization was 38.8 and 32.7 months,
A study conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) in 176 patients with MM who had responded to
melphalan and prednisone found that interferon alfa maintenance therapy was associated with a statistically significant improvement
in duration of response and overall survival, compared with no treatment12; however, maintenance therapy with interferon alfa also
led to considerable toxicity that resulted in a dose reduction in 58% of patients and treatment discontinuation in 14% of patients.12
In two small studies—US Intergroup Trial S9321 (n=242) and SWOG 8624 (n=193)—no difference in progression-free survival (PFS) or
overall survival was noted with interferon alfa maintenance therapy versus observation only in patients with MM who had attained
a reduction in tumor burden of ≥75% after initial treatment.10,17
In general, interferon alfa has been associated with modest improvement in remission duration, and in a few studies, overall survival; however,
this therapy has been associated with high toxicity and poor tolerability and, therefore, interferon maintenance is rarely used
Corticosteroids as Maintenance Therapy
Several clinical trials have investigated the use of corticosteroids as maintenance therapy, but definitive conclusions cannot be
drawn from the findings.9 SWOG 9210 was the first study to investigate the role of glucocorticoids used alone as maintenance
therapy in MM.5 In the study, which compared two doses of alternate-day prednisone (10 mg vs 50 mg) as remission maintenance
therapy in 126 patients with MM who had responded to induction therapy (either vincristine, doxorubicin, dexamethasone
with prednisone [VAD-P] or VAD-P with quinine [VAD-P/Q]),5 median PFS was significantly longer with high-dose than
low-dose prednisone (14 vs 5 months, respectively; P=.003), as was median overall survival
(37 vs 26 months, respectively; P=.05).5 Adverse events were similar in the two treatment arms
(ie, 13 patients experienced toxicity of ≥3 grade in each arm).5
In a randomized trial comparing dexamethasone versus interferon alfa as maintenance therapy in 84 patients who had responded
to primary therapy with oral melphalan and intermittent high-dose dexamethasone, median remission was 10 months with both regimens,
and side effects were rare and mild18; median survival from initiation of maintenance therapy was 52 and 58 months with
interferon alfa and dexamethasone, respectively.18 In the NCIC CTG MY.7 study comparing dexamethasone versus observation
as maintenance therapy in 292 patients with MM who had responded to induction therapy with melphalan plus dexamethasone
or melphalan plus prednisone, median PFS was 2.8 versus 2.1 years, respectively (hazard ratio [HR] = 0.61; 95% confidence
interval [CI], 0.47-0.79; P=.0002); however, no difference was observed in median overall survival (4.1 vs. 3.8 years,
respectively; HR, 0.88; 95% CI, 0.65-1.18; P=.4).20
Combination maintenance therapy consisting of a glucocorticoid plus interferon alfa has been shown to improve both progression-free
and overall survival in patients with MM compared with interferon alfa alone.5 In SWOG 9028—a study in 89 patients with MM who
had attained complete or partial remission after VAD induction—PFS with prednisone plus interferon alfa versus interferon alfa alone
was 19 and 9 months, respectively (P=.008); median survival was 57 and 46 months, respectively (P=.36).19 In general, maintenance
therapy was well tolerated, and toxicity of ≤3 grade, which included malaise and leukopenia, was usually correlated with interferon
Again, tolerability and toxicity have prevented widespread use of steroids as maintenance therapy. This, and the recent recognition
of the negative impact steroids have in the newly diagnosed setting, especially in combination with novel agents, limits the use
of steroids in myeloma therapy in general.10,18,19
Thalidomide as Maintenance Therapy
...the use of thalidomide as induction therapy,
as well as in relapsed and refractory MM, and summarize the rationale for its use as maintenance therapy.
Thalidomide was the first novel agent to be studied in the maintenance setting.9 In a recent meta-analysis
of three randomized controlled trials, the use of thalidomide maintenance therapy following ASCT in patients with previously untreated
MM was associated with a significant overall survival advantage (HR, 0.49; 95% CI, 0.32-0.74),21 but also an increased relative
risk (RR) of venous thromboembolism (RR, 1.95; 95% CI, 1.15-3.30).21
Most studies investigating thalidomide maintenance therapy have focused on younger patients who have completed ASCT,
a setting in which such therapy has led to improvement in PFS and mixed results with regard to overall
survival (see Table 1).
In the Intergroupe Francophone du Myélome (IFM) 99-02 trial in 708 patients with MM (aged 65 years or younger) who were nonprogressing
after high-dose therapy followed by double ASCT, maintenance therapy with pamidronate plus thalidomide led to a complete or very good
partial response in 67% of patients, compared with rates of 55% and 57% in patients receiving no maintenance and pamidronate alone,
respectively.1 Of interest, the benefit of thalidomide in terms of event-free survival was substantial in patients who did not have
a deletion of chromosome 13; in contrast, thalidomide was not effective in patients who had a deletion of chromosome 13.1
The main adverse events associated with thalidomide included neuropathy (68%), fatigue (34%), and constipation (20%); adverse
events led to discontinuation of thalidomide in 39% of patients.1
In another study—243 patients (median age, 57 years) who had achieved stable disease or better with induction chemotherapy,
high-dose melphalan therapy, and ASCT—were assigned to either maintenance prednisolone only or maintenance prednisolone plus
consolidation thalidomide.22 At median follow-up of 3 years, estimated PFS was 42% versus 23% in the thalidomide and control arms,
respectively (P=.001),22 and estimated overall survival was 86% and 75%, respectively (P=.004).22
In the NCIC CTG MY.10 study, a randomized trial comparing daily thalidomide plus alternate-day prednisone (T/P) as maintenance therapy
versus observation only following ASCT in 332 patients with MM (median age, 58 years), T/P did not significantly prolong overall
survival (HR, 0.77; 95% CI, 0.53-1.13; P=.18); the 4-year overall survival rate was 68% and 60%, respectively.23 Although median
PFS was significantly improved in the T/P versus observation-only arm (28 and 17 months, respectively; HR, 0.56; 95% CI, 0.43-0.73; P<.0001),
grade 3/4 nonhematologic toxicity and common toxicities of all grades were higher with treatment; the 4-year PFS rate was 32% versus 14%,
Another study investigated the efficacy of thalidomide as maintenance or salvage therapy versus no treatment in 112
patients with MM (median age, 53 years) who had undergone ASCT.24 Patients receiving thalidomide post-transplantation had improved median
survival, compared with those in the no-treatment group (65.5 vs. 44.5 months, respectively; P=.09); additionally, overall survival was
longer in patients who received thalidomide as maintenance therapy than as salvage therapy (65 vs. 54 months, respectively; P=.05).24
In contrast to the above randomized trials, where thalidomide was given after ASCT, the Total Therapy 2 (TT2) trial randomized newly
diagnosed MM (n=668) to thalidomide upfront and through various stages of induction, tandem transplants, consolidation and maintenance;
about 80% of the patients were younger than 65 years. At median follow-up of 42 months, complete response was 62% in patients receiving
thalidomide and 43% in those not receiving thalidomide (P<.001); however, 5-year overall survival was about 65% in both study arms (P=.90).
The incidence of severe peripheral neuropathy and deep vein thrombosis was higher in the thalidomide group than in the control group.
Also of note, an update to the TT2 trial showed that thalidomide improved survival and duration of complete remission in patients
with high-risk cytogenetics. At 7 years from onset of complete remission, 45% of patients with cytogenetic abnormalities who
received thalidomide versus 20% of patients in the control arm remained relapse free (P=.05).25
The role of thalidomide as maintenance therapy in older patients who are ineligible for ASCT remains to be clearly elucidated.11
One recent study assessed the effect of thalidomide plus interferon alfa versus interferon alfa alone as maintenance therapy in
128 elderly patients with MM who had stable disease or better after induction therapy with either thalidomide plus dexamethasone
or melphalan plus prednisolone.11 PFS was significantly longer in patients receiving thalidomide plus interferon alfa than
interferon alfa alone (27.7 vs. 13.2 months; P=.0068)11; however, overall survival was similar in the two groups
(52.6 vs. 51.4 months; P=.81) and did not differ between older and younger patients (P=.39).11
In a study in 103 elderly patients with MM who had achieved at least a minor response after conventional induction therapy
with thalidomide, dexamethasone, and pegylated liposomal doxorubicin, PFS and overall survival were significantly better with
thalidomide plus dexamethasone (TD) than interferon alfa plus dexamethasone (ID) maintenance therapy.6 Two-year PFS was 63% in
patients in the TD arm versus 32% in the ID arm (P=.024); overall survival was 84% versus 68%, respectively (P=.030).6 Main
adverse events were peripheral neuropathy and constipation in the TD arm and fatigue, anorexia, and hematological toxicity
in the ID arm.6
Investigators have also studied the effectiveness and tolerability of different doses of thalidomide used as maintenance therapy.
In a phase 2 study in 100 patients with nonprogressive MM investigating thalidomide maintenance therapy in five dose-escalating
cohorts (ie, 50, 100, 200, 250, and 300 mg) after high-dose melphalan-based ASCT, dosage did not affect disease outcome,
but had a substantial effect on toxicity.26 At median follow-up of 32.3 months, 77 patients had discontinued thalidomide
because of side effects (n=53), disease progression (n=23), or financial reasons (n=1).26 The main toxicity, peripheral
neuropathy, led to discontinuation of maintenance therapy in nearly one-third of patients.26 At 3 years, PFS and overall
survival were 41% and 76%.26 Thalidomide maintenance doses >200 mg were mostly unattainable.26
A study in 31 patients with MM who were nonprogressing after ASCT examined the tolerability and efficacy of maintenance therapy
with thalidomide, starting with 50 mg/day and escalating in 50-mg increments, as tolerated, to a maximum dose of 200 mg/day.27
At 1 and 2 years, complete or very good partial response was reported in 65% and 42% of patients, respectively27; median PFS
was 20.8 months, and median overall survival was longer than 5 years.27 The median tolerated dose of thalidomide was 100 mg/day27;
only 17 patients attained dosing at 200 mg/day.27 The main reason for intolerance to thalidomide was sensory neuropathy.27
A major limitation of thalidomide maintenance is the toxicity profile of the drug, as mentioned above, and its association with poor
compliance. Lower doses of thalidomide are better tolerated and can be given for prolonged periods of time; however,
data for differences between dose/duration and outcome are lacking.27 More importantly, with the recent data for lenalidomide in
the maintenance setting, thalidomide is falling out of favor as a therapy for MM patients, as lenalidomide has demonstrated an
acceptable tolerability and ease of long-term use.28
...a short case study of a patient with MM who could potentially be a candidate for maintenance therapy.
Lenalidomide as Maintenance Therapy
Lenalidomide as maintenance therapy has been investigated in 3 key randomized phase 3 studies, 2 of which were for
transplant-eligible patients (CALGB 100104 and IFM 2005-02) and produced results that led to a category 2A recommendation by
the NCCN panel (see Table 2).3
The third trial, MM-015, included ASCT-ineligible patients.3
The first trial, CALGB 100104, compared maintenance lenalidomide (10 mg daily escalated to 15 after 3 months) versus placebo
after ASCT in 460 patients (age, 70 years or younger) with stable disease or better and showed a median time to progression
of 42.3 in lenalidomide-treated patients and 21.8 months in the placebo arms29,30; that resulted in unblinding of the
results by the Data Safety Monitoring Committee (DSMC) and crossover for those receiving placebo.29,30 A recent update
showed that lenalidomide was associated with a 61% reduction in risk of disease progression or death
(estimated HR, 0.39; 95% CI, 0.27-0.56; P<.0001) at median post-ASCT follow-up of 17.5 months.29
Pooled grade 3 and higher adverse events attributed to lenalidomide included: thrombocytopenia (11% vs. 3%, respectively; P=.01),
neutropenia (44% vs. 8%, respectively; P<.0001), anemia (5% vs. 1%, respectively; P=.0082), and all infections
(16% vs. 3%, respectively, P<.0001).29
In the IFM 2005-02 trial, 614 patients with MM (age, younger than 65 years) who had nonprogressive disease
after ASCT received consolidation therapy with lenalidomide (25 mg daily) for 2 months, followed by maintenance
therapy with either lenalidomide (10-15 mg daily) or placebo.31,32 Median PFS from time of randomization and
diagnosis was 24 and 34 months, respectively, in patients receiving placebo, compared with 42 and 52 months,
respectively, in patients receiving lenalidomide maintenance therapy (HR = 0.5; P<10-8).32
The study was stopped by the DSMC, but with no crossover for placebo patients.32
The third trial, MM-015, from Italy, randomized 459 ASCT-ineligible patients with newly diagnosed MM (aged 65 years or older) to
receive one of three regimens: (1) melphalan, prednisone, and lenalidomide (MPR) induction therapy followed by continuous
lenalidomide maintenance therapy; (2) fixed duration MPR; or (3) fixed duration MP.33,34 Two-year PFS was 55% and 16%
with MPR-R versus MP, respectively.34 Overall response rates with MPR followed by continuous lenalidomide maintenance
therapy versus fixed duration MP were 77% and 50%, respectively (P<.001); complete response rates were 16% versus 4%,
respectively (P<.001).34 In addition, overall risk of disease progression was reduced by 58% with MPR followed by continuous
lenalidomide maintenance therapy versus fixed duration MP (HR, 0.423; P<.001), and 2-year PFS was 55% versus 16%, respectively.34
Grade 3/4 neutropenia, thrombocytopenia, and anemia were reported in 71%, 38%, and 24% of patients, respectively, receiving MPR followed
by continuous lenalidomide maintenance therapy versus 30%, 14%, and 17% of patients, respectively, receiving fixed duration MP.34
All 3 trials have not matured enough to establish survival benefits for patients. Additionally, in all 3 trials, there was an
increased risk of second cancers (Table 3) including breast, prostate, colon, as well as leukemia and Hodgkin and
non-Hodgkin lymphomas in patients receiving lenalidomide compared with those on placebo.29-34
Bortezomib as Maintenance Therapy
...the mechanism of action of bortezomib and compare its side effect profile with that of standard chemotherapeutic agents.
The use of the proteasome inhibitor bortezomib35,36 as maintenance therapy is currently under investigation
in several clinical trials (see Table 4).3
In the US community-based, randomized, open-label, multicenter, phase 3b UPFRONT study, 300 elderly patients who were ineligible for high-dose
therapy and ASCT were randomized to one of three bortezomib-based induction therapies (bortezomib-dexamethasone, bortezomib-thalidomide-dexamethasone,
or bortezomib-melphalan-prednisone) followed by 5 cycles of bortezomib maintenance (bortezomib 1.6 mg/m2 days 1, 8, 15, and 22 of a 35-day cycle).37
After eight cycles of induction therapy, overall response in the bortezomib-dexamethasone, bortezomib-thalidomide-dexamethasone,
and bortezomib-melphalan-prednisone groups was 68%, 78%, and 71%, respectively; after five cycles of bortezomib maintenance therapy,
overall response increased to 71%, 79%, and 73%, respectively, with no increase in the frequency of peripheral neuropathy.37
The randomized phase 3 HOVON-65/GMMG-HD4 trial compared the efficacy of induction therapy with standard VAD followed by high-dose melphalan
with ASCT and maintenance therapy with 50 mg daily of thalidomide for 2 years (arm A) versus induction therapy with bortezomib, doxorubicin,
and dexamethasone followed by high-dose melphalan with ASCT and maintenance therapy with 1.3 mg/m2 of bortezomib twice weekly for
2 years (arm B) in 613 evaluable patients with newly diagnosed MM.38 Maintenance therapy was started by 67% of patients in arm A versus
57% of patients in arm B; protocol deviations occurred in 64% and 47% of patients, respectively, because of toxicity, progression,
or other reasons.38 At 36 months, PFS was 42% in arm A and 46% in arm B.38
A randomized phase 3 study in 511 patients with MM (aged 65 years or older) who were ineligible for high-dose therapy plus ASCT found that
treatment with bortezomib-melphalan-prednisone-thalidomide (VMPT) followed by maintenance therapy with bortezomib-thalidomide (VT) was superior
to VMP without maintenance therapy.39 At 3 years, overall survival was 89% and 87% with VMPT followed by maintenance therapy with VT versus
VMP without maintenance therapy (HR, 0.92; 95% CI, 0.53-1.60; P=.77)39; estimated 3-year PFS was 56% and 41%, respectively
(HR, 0.67; CI, 0.50-0.90; P=.008).39 Grade 3 to 4 neutropenia occurred in 38% and 28% of patients receiving VMPT followed by maintenance
VT versus VMP, respectively (P=.02).39
A prospective, multicenter, randomized trial recently investigated induction therapy with VMP versus VTP followed by maintenance
therapy with VT versus VP in elderly patients (older than 65 years of age) with MM.40 In 143 evaluable patients after maintenance therapy,
complete response in the VT and VP arms was 46% and 38%, respectively.40 The trend in terms of time to progression at median duration
of maintenance therapy (13 months) favored the VT arm over the VP arm (84% vs. 71%, respectively; P=.05); 1-year overall survival
was 92% versus 89%, respectively.40
In a study in 49 patients with advanced MM (median age, 71 years) who were responsive to salvage bortezomib-containing regimens
and had measurable disease, the use of bortezomib plus dexamethasone as maintenance therapy was shown to be effective and
well tolerated. Median time to progression was 17 months; at 1 year, PFS and overall survival were 61% and 79%,
respectively.36 Three patients experienced grade 2 neuropathy, which led to bortezomib dose reduction;
no grade 3 or 4 neuropathy or hematologic adverse events were reported.36
...the rationale for the use of maintenance therapy in appropriate patients with MM.
The Use of Novel Agents as Consolidation Therapy
Consolidation therapy is maintenance given after induction therapy, but the doses are higher and are usually given for a defined period
that varies from 4 cycles in one year to 2 intensive cycles over 2 months.
In a randomized phase 3 study in 474 newly diagnosed patients with MM, investigators compared VTD with TD as induction
(three 21-day cycles) and consolidation therapy (two 35-day cycles) before and after double ASCT to analyze response
after all phases of treatment and survival.1,3,41 The centrally reassessed complete response/near complete response rate
was significantly higher in patients receiving VTD than TD after induction therapy (30% vs. 10%; P<.0001), double
ASCT (54% vs. 42%, respectively; P=.008), and consolidation therapy (60% vs. 44%, respectively; P=.001).42 A per-protocol
analysis in 323 patients showed that overall upgraded response with VTD and TD as consolidation therapy was observed
in 55% versus 37% of patients, respectively (odds ratio, 1.15-3.77; P=.01).42 At median follow-up of 31 months, median
PFS was 42 months in patients receiving TD and was not yet reached in those receiving VTD.42 Furthermore, a molecular
substudy using qualitative and quantitative polymerase chain reaction analysis in 67 and 45 evaluable patients,
respectively, showed that two 35-day cycles of VTD consolidation after double ASCT versus TD consolidation was
associated with a significant increase in the rate of molecular remission and a significant reduction in the burden
of residual myeloma cells.43
In another study—in 46 evaluable patients younger than age 65 years with de novo MM—early consolidation with VTD after thalidomide
and/or bortezomib induction therapy improved response in nearly 40% of patients.44 Overall, consolidation therapy with two cycles
of VTD, started within 3 months of ASCT, led to complete response in 36% of patients, complete response/near complete response
in 68% of patients, and very good partial response in 91% of patients.44
Data from the open-label, phase 2 IFM 2008 study in 31 evaluable patients younger than age 65 years with newly diagnosed
MM showed that induction therapy with bortezomib/lenalidomide/dexamethasone (VRD) followed by ASCT and VRD consolidation
therapy yielded responses of high quality.45 After consolidation, stringent complete response was achieved in 5 patients,
and complete response was achieved in 5 patients.45 The overall response rate after consolidation was 94%.45
A recent study assessing the prognostic implications of cumulative dosing and premature discontinuation of the components of
VTD from the outset of protocol therapy into maintenance therapy supports the upfront usage of all active agents in a
dose-dense and dose-intense manner, as in the Total Therapy 3 (TT3) protocol.46 In TT3, the addition of bortezomib,
plus the shortening of induction and consolidation therapies to 2 cycles (from 4 cycles in TT2),47 led to
The role of maintenance therapy after conventional chemotherapy or high-dose therapy followed by ASCT in patients with
MM is evolving.1,5,9,10 At present, clinical trials established improvement of PFS and, in many studies,
OS with the use of thalidomide; the data for lenalidomide is immature to show OS difference, but established
an impressive improvement of EFS.9 The addition of bortezomib in consolidation/limited maintenance therapy has
shown improvement in the depth of response, including in many cases of molecular remission, which may establish
a role for such intervention in eliminating minimal residual disease, a goal that is rarely obtained in
Additional studies are needed to determine optimal dose and duration of any maintenance therapy
and to identify patients who would most benefit from such treatment. Additionally, more research is needed to
determine the impact of such therapy on the pattern of relapse and the response to salvage therapy.9
The current NCCN recommendations for maintenance therapy in MM include interferon alfa (category 2B);
corticosteroids (category 2B); thalidomide (category 1) with or without prednisone (category 2B); and
lenalidomide (category 2A). All are rarely used today because of side effects, as they are replaced mostly
by lenalidomide (category 2A).3 Use of the proteasome inhibitor bortezomib as maintenance therapy lacks a
formal NCCN recommendation.3
- Attal M, Harousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289-3294.
- Magarotto V, Palumbo A. Evolving role of novel agents for maintenance therapy in myeloma. Cancer J. 2009;15:494-501.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Multiple myeloma. Version 1.2011. July 27, 2010. Available at: http://www.nccn.org. Accessed February 10, 2011.
- Ghobrial IM, Stewart AK. ASH evidence-based guidelines: what is the role of maintenance therapy in the treatment of multiple myeloma? Hematology. 2009:587-589.
- Berenson JR, Crowley JJ, Grogan TM, et al. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood. 2002;99:3163-3168.
- Offidani M, Corvatta L, Polloni C, et al. Thalidomide-dexamethasone versus interferon-alpha-dexamethasone as maintenance treatment after ThaDD induction for multiple myeloma: a prospective, multicentre, randomized study. Br J Haematol. 2008;144:653-659.
- Dimopoulos MA, Terpos E. Multiple myeloma. Ann Oncol. 2010;21(suppl 7):vii143-vii150.
- Anderson KC, Kyle RA, Rajkumar SV, et al. Clinically relevant end points and new drug approvals for myeloma. Leukemia. 2008;22:231-239.
- Badros AZ. The role of maintenance therapy in the treatment of multiple myeloma. J Natl Comp Cancer Netw. 2010;8(suppl 1):S21-S27.
- Salmon SE, Crowley JJ, Grogan TM, Finley P, Pugh RP, Barlogie B. Combination chemotherapy, glucocorticoids, and interferon alfa in the treatment of multiple myeloma: a Southwest Oncology Group study. J Clin Oncol. 1994;12:2405-2414.
- Ludwig H, Adam Z, Tóthová E, et al. Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma. Haematologica. 2010;95:1548-1554.
- Browman GP, Bergsagel D, Sicheri D, et al. Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1995;13:2354-2360.
- Fritz E, Ludwig H. Interferon-alpha treatment in multiple myeloma: meta-analysis of 30 randomised trials among 3948 patients. Ann Oncol. 2000;11:1427-1436.
- Myeloma Trialists' Collaborative Group. Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol. 2001;113:1020-1034.
- Mandelli F, Avvisati G, Amadori S, et al. Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med. 1990;322:1430-1434.
- Bladé J, San Miguel JF, Escudero ML, et al. Maintenance treatment with interferon alfa-2b in multiple myeloma: a prospective randomized study from PETHEMA (Program for the Study and Treatment of Hematological Malignancies, Spanish Society of Hematology). Leukemia. 1998;12:1144-1148.
- Barlogie B, Kyle RA, Anderson KC, et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol. 2006;24:929-936.
- Alexanian R, Weber D, Dimopoulos M, et al. Randomized trial of alpha-interferon or dexamethasone as maintenance treatment of multiple myeloma. Am J Hematol. 2000;65:204-209.
- Salmon SE, Crowley JJ, Balcerzak SP, et al. Interferon versus interferon plus prednisone remission maintenance therapy for multiple myeloma: a Southwest Oncology Group study. J Clin Oncol. 1998:16:890-896.
- Shustik C, Belch A, Robinson S, et al. A randomized comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7. Br J Haematol. 2006;136:203-211.
- Hicks LK, Haynes AE, Reece DE, et al. A meta-analysis and systematic review of thalidomide for patients with previously untreated multiple myeloma. Cancer Treat Rev. 2008;34:442-452.
- Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009;27:1788-1793.
- Stewart AK, Trudel S, Bahlis N, et al. A randomized phase III trial of thalidomide and prednisone as maintenance therapy following autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM): the NCIC CTG MY.10 trial. Abstract presented at: 2010 American Society of Hematology Annual Meeting; Orlando, FL; December 4-7, 2010. Abstract 39.
- Brinker BT, Waller EK, Leong T, et al. Maintenance therapy with thalidomide improves overall survival after autologous hematopoietic progenitor cell transplantation for multiple myeloma. Cancer. 2006;106:2171-2180.
- Barlogie B, Pineda-Roman M, van Rhee F, et al. Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood. 2008;112:3155-3121.
- Feyler S, Rawstrom A, Jackson G, et al. Thalidomide maintenance following high-dose therapy in multiple myeloma: a UK myeloma forum phase 2 study. Br J Haematol. 2007;139:429-433.
- Chang JE, Juckett MB, Callander NS, et al. Thalidomide maintenance following high-dose melphalan with autologous stem cell support in myeloma. Clin Lymphoma Myeloma. 2008;8:153-158.
- Zeldis JB, Knight RD, Jacques C, Tozer A, Bizzari JP. Lenalidomide in multiple myeloma: current role and future directions. Expert Opin Pharmacother. 2010;11:829-842.
- McCarthy PL, Owzar K, Anderson KC, et al. Phase III Intergroup study of lenalidomide versus placebo maintenance therapy following single autologous hematopoietic stem cell transplantation (AHSCT) for multiple myeloma: CALGB 100104. Abstract presented at: 2010 American Society of Hematology Annual Meeting; December 4-7, 2010; Orlando, FL. Abstract 37.
- McCarthy PL, Owzar K, Anderson KC, et al. Phase III Intergroup study of lenalidomide versus placebo maintenance therapy following single autologous stem cell transplant (ASCT) for multiple myeloma (MM): CALGB 100104. Abstract presented at: 2010 American Society of Clinical Oncology Annual Meeting; June 4-8, 2010; Chicago, IL. Abstract 8017.
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