Haematologica 2003 - Supplements

proportion of bone abnormality. IgD myelomas also had higher
β2 microglobulin levels than the common myelomas. IgD
myelomas presented with a significant reduction in haemoglobin
whereas NS had significantly raised haemoglobins in comparison
to the common myelomas. There was no difference in the
median time from diagnosis to transplantation for IgD, NS and
common myelomas. Both IgD and NS myeloma had a higher
incidence of complete remission at conditioning than the common
myelomas. The median survival for patients with IgD myeloma
was 42.5 months (p = 0.003 log rank test) while that for NS was
50.0 months (p = 0.80). 11 patients with IgM myeloma were
identified, (9 male 2 female) 8 (of 9) had stage 111 disease, all
but one had PBSC transplant with none receiving TBI. Median
time from diagnosis to transplant was 8 months, survival ranged
from 0.4 to 30.2 months. There were 5 patients with IgE
myeloma, (3 male, 2 female), 2 patients had bone marrow
transplants and 3 peripheral blood stem cells, only 1 received
TBI, the median time to transplantation was 7 months and
survival ranged from 0.3 to 33.9 months.
These data sets confirm that patients with IgD myeloma have a
poor prognosis even if treated with transplantation and both IgE
and IgM would appear to be similar; in contrast NS myeloma
appears to have a similar outcome to the common myelomas.
262
PROGNOSTIC FACTORS AT THE TIME OF SINGLE
AUTOTRANSPLANTATION WITH 200 MG/M2
MELPHALAN: A SINGLE-CENTER STUDY OF 451
MYELOMA (MM) PATIENTS
Bhawna Sirohi, Ray Powles, Jayesh Mehta, Samar
Kulkarni, Clive Horton, Radovan Saso, Seema Singhal
Royal Marsden NHS Trust
McElwain & Powles (Lancet, 1983;2:822-4) pioneered the use of
high-dose melphalan in the patients with myeloma and
documented complete remission for the first time in these
patients. High-dose melphalan 200mg/m2 (HDM200)has been
shown to be the most optimal regimen for consolidation therapy
in patients with MM (Moreau P et al Blood 2002; 99:731-5). We
present the largest series of MM patients treated with HDM200
and a single unpurged autograft. 451 patients (31-75 y, median
53; 154F,297M; 73% stage III;94% IgG; 66% ≥2 bone lesions)
were treated from 1985 to 2001.. The median B2M was 2.3mg/L
(0.1-54.6), median creatinine 81µmol/L (43-732), median
albumin 39g/L (22-48). 49% presented after induction elsewhere
and 51% were untreated. Therapy was: Induction (VAMP/C-
VAMP for untreated patients) to 1 cycle beyond maximum
response → Marrow or G-CSF-mobilized PBSC harvest →
HDM200 → Interferon-2b. Before HDM200, 75 (17%) patients
were in CR, 286 (63%) in PR and 90 (20%) were NR. A further
192 (43%) went into CR during HDM200 so that the total CR
rate after HDM was 59% (266/451). The overall response rate
was 407/451 (91%).27 (5.9%) patients died at a median of 21
days.The median OS for the whole group was 5.7 years (95% CI-
5.1-6.8) and the median EFS was 2.3 years (95% CI- 2.1-2.7).
246/451 (55%) patients have relapsed at a median of 2.8 years
(95% CI- 2.3-3.3). These results are equivalent to tandem
transplantation. Pre-transplantation variables chosen to be
included in Cox analysis were age, sex, Ca, B2M, albumin,
creatinine , immunologic type of myeloma (IgG/IgA vs others),
performance status ( 0 vs rest according to the Karnofsky scale),
disease stage at HDM200 (CR vs rest). The results are shown in
Table.
Event Adverse Variables RR 95% CI P value
at HDM200
OS Age ≥ 53 1.63 1.22-2.18 2.3 3.49 1.37-8.86 0.003
Given the importance of achieving CR at the time of high-dose
therapy, intensification of induction treatment may be of benefit
and makes the case for administering induction therapy to
maximum response. No other factor influenced relapse. We
conclude that HDM200 results in excellent outcome in myeloma
and should be considered as the standard of care and this also
raises questions about the use of tandem-autotransplantation as
routine therapy.
263
IMPACT OF AGE ON SURVIVAL AFTER INTENSIVE
THERAPY IN NEWLY DIAGNOSED MYELOMA.
Lenhoff S, Hjorth M, Lanng-Nielsen J, Westin J, Wislöff F
For the Nordic Myeloma Study Group (NMSG).
Intensive therapy, including autologous stem cell transplantation
(ASCT), is superior to conventional therapy in newly diagnosed
myeloma patients below 60 years. Above that age the value is
less clear.
In 1998 the NMSG initiated a population based, prospective trial
(#7/98) aiming to study the effect of age on event-free survival
and survival, and to compare survival to a conventionally treated
historic control group. Newly diagnosed patients up to the age of
65 years were included in an intensive therapy protocol with four
phases; I) VAD x 3-4; II) Cyclophosphamide 2g/sqm, G-CSF
(filgrastim) and stem cell harvest; III) Melphalan 200 mg/sqm,
stem cell infusion and G-CSF; IV) Interferon maintenance.
Double ASCT was optional.
From Jan 1998 to June 2000, 452 patients were registered. 414
(92%) were included in the intensive therapy protocol (=Intensive
Therapy Group (ITG)). 294 were below 60 years (=ITG-60) and
120 were 60-64 years (=ITG-65).
The historic control group was derived from a previous
population based NMSG trial (#4/90) which included patients
1990-1992. Initial therapy was mainly melphalan and prednisone
+/- interferon. Of the 281 patients below 65 years registered in
this trial, 243 (86%) fulfilled the eligibility criteria for intensive
therapy stated in #7/98 (=Control Group (CG)). 146 were below
60 years (=CG-60) and 97 were 60-64 years (=CG-65).
In the ITG-60, 261 patients (89%) were actually transplanted
(80% single ASCT, 18% double ASCT and 2% allogeneic SCT).
In the ITG-65, 98 patients (82%) were transplanted (84% single
and 16% double ASCT). Major response rate (CR+PR) was 88%
in the ITG-60 and 80% in the ITG-65 calculated on an intentionto-treat
basis. Event-free survival and survival at 3 years were
50% (95%CI 44-57%) and 78% (72-83%) in the ITG-60,
compared to 33% (23-42%) and 65% (54-75%) in the ITG-65. In
a multivariate analysis of the entire ITG, two variables were
significantly associated with event-free survival and survival;
beta-2-microglobuline at diagnosis and age < or > 60 years.
The survival in the ITG-60 was prolonged compared to the CG-
60 with a risk ratio of 0.44 (95%CI 0.31-0.63; p