Page 1581 - Hematology_ Basic Principles and Practice ( PDFDrive )

1408 Part VII Hematologic Malignancies

TABLE Results of Large Randomized Studies Comparing Standard-Dose Therapy With High-Dose Therapy
86.18
Authors Therapy Number of Patients CR (%) EFS (Median Mo) OS (Median Mo)
Attal et al Conventional 100 5 a 18 a 37 a
HDT 100 22 27 52
Fermand et al Conventional 96 — 18.7 a 50.4 b
HDT 94 — 24.3 55.3
Blade et al Conventional 83 11 a 34.3 a 66.9 b
HDT 81 30 42.5 67.4
Child et al Conventional 200 8.5 a 19.6 a 42.3 a
HDT 201 44 31.6 54.8
Barlogie et al Conventional 255 15 b 21 b 53 b
HDT 261 17 25 58
a Significant difference.
b No significant difference.
CR, Complete remission; EFS, event-free survival; OS, overall survival; HDT, high-dose therapy.

TABLE Single Versus Double Autologous Stem Cell Transplant for Newly Diagnosed MM
86.19
Study ASCT Number of Patients CR (%) a Median EFS (Mo) Median OS (Mo)
Attal et al Single 199 42 b 25 48
p = NS p = .03 p = .01
(IFM94) Double 200 50 b 30 58
Fermand et al Single 94 42 a No difference No difference
p = NS
(MAG95) Double 99 37 a
Sonneveld et al Single 148 13 20 55
p = .002 p = .02 p = NS
(HOVON24) Double 155 28 22 50
Cavo et al Single 115 35 Significant prolongation of EFS 59
(Bologna 96) Double 113 p = NS with double-SCT p = NS
48 73
a CR + minimum residual disease.
b CR + very good partial response.
ASCT, Autologous stem cell transplant; CR, complete remission; EFS, event-free survival; IFM, Intergroupe Francophone du Myélome; NS, not significant; OS, overall
survival; SCT, stem cell transplant.

of the initial therapy. This allowed for flexibility in the timing of transplant, and three of the four studies showed improvement in PFS,
transplant to suit the patient’s clinical situation and preference. but only one study showed an improvement in the OS. The French
33
A metaanalysis of primary data obtained from the three French trial (IFM 94 ) showed the benefit of a second transplant only for
studies (IFM 90, MAG 90, and MAG 91) showed no difference in patients not in VGPR or better after the first transplant. In the era
the OS between standard therapy and HDT arms. Likewise, authors of novel agents, a VGPR or better can be obtained before transplant,
of another metaanalysis using data culled from nine randomized and therefore a second transplant is seldom used outside the setting
clinical trials reported in the literature showed no survival benefit for of a clinical trial (Table 86.20).
HDT and stem cell transplant. These data are in direct contrast to In the era before introduction of novel agents, induction regimen
the metaanalysis using the Swedish Cancer Registry and SEER data had only a minimal role because CRs were uncommon (less than 5%)
with improvement in 5-year relative survival ratios for younger with high-dose dexamethasone or VAD chemotherapy. Thus HDT
patients primarily due to the introduction of HDT and stem cell played a critical role in achieving favorable CR and VGPR rates and
transplant in the 1990s. prolonged durability of unmaintained responses. The availability of
On the presumption that therapy with a single alkylating agent novel agents has dramatically changed this paradigm. Novel agents
at MTD may not be adequate for disease eradication, Barlogie pio- have improved VGPR or better before stem cell transplant, allowing
neered a tandem transplant approach as part of his total therapy for posttransplant consolidation and maintenance. Whether novel
approach for the treatment of MM in 1989 (Total Therapy 1) and agents can supplant HDT and stem cell transplant is an important
reported promising results without increased treatment-related question that has yet to be answered.
morbidity or mortality. Single HDT resulted in a CR rate well under
25% in most trials. These investigators tried to improve the results
by providing a second consecutive high-dose melphalan and stem cell Induction Therapy With Novel Agents
transplant (tandem transplant).
There have been four large randomized clinical trials comparing Randomized clinical trials have shown that combined thalidomide
the role of tandem autotransplant against a single episode of HDT and dexamethasone therapy is equivalent to VAD chemotherapy. The
and stem cell transplant (Table 86.19). All four studies showed Dutch HOVON 50 trial researchers compared thalidomide during
improvement in the depth of response (VGPR) following a tandem the induction phase and as maintenance following HDT and stem