Haematologica 2003 - Supplements

411
Dendritic Cell-Based Idiotype Vaccination for Primary
Systemic Amyloidosis
M.Q. Lacy, S. Geyer, N. Foster, P. Wettstein, A.
Dispenzieri, D.A. Gastineau, P.R.Greipp, R. Fonseca, J.
Lust, T. Witzig, S.V. Rajkumar, S Zeldenrust, M. Peshwa,
R.A. Kyle, M.A. Gertz
Mayo Clinic
Introduction: Introduction: Immunotherapy is most likely to work
in a setting of low tumor burden, making vaccine strategies
attractive as therapy for primary systemic amyloidosis (AL). A
clinical trial of dendritic cell-based idiotype vaccination as
therapy for AL was undertaken.
Methods: Between September 1998 and December 2001 a novel
immunotherapeutic, APC8020 (Mylovenge), was studied as
therapy after for AL. Mylovenge is prepared from autologous
antigen presenting cells (APC), including dendritic cells, partially
purified from an unmobilized leukapheresis product by gradient
density isolation and then incubated for two days with autologous
serum containing M protein. Treatment was given intravenously
in weeks 0, 2, 4, and 16. Eligibility criteria included: Histologic
diagnosis of amyloidosis, quantifiable M-protein in the serum,
age >18 years, ECOG Performance Status (PS) 0- 2, leukocytes
>1,500/µL, platelets >50,000/µL, bilirubin >5 x the upper limits
of normal, creatinine >5.0 mg/dL , adequate venous access for
apheresis. Responses were evaluated according to our previously
published criteria.
Results: Fifteen patients were enrolled. Median age was 61 years
(range 42-76 years). Thirteen had prior therapy (range 1-5 prior
regimens). Biopsy positive sites included: liver (1), kidney (7),
gastrointestinal tract (3), bone marrow (7), fat (10), lung (1).
Associated monoclonal proteins included G (3), G (7), M
(2), M (2) and A (1). Previous therapies included: stem cell
transplant in 4 and chemotherapy in 11. Organ involvement
included: cardiac (4), pulmonary (1), renal (8), peripheral nerve
(4), autonomic nerve (1). Four patients had concurrent
malignancies, two with multiple myeloma and two with
Waldenstrom’s macroglobulinemia. Fifty-five infusions were
done in the 15 patients. Toxicity was modest. There were ten
adverse events, of which four were attributed to the underlying
disease. Best responses consisted of: major response (1), minor
response (1), stable disease (11) and progression (2). The major
response consisted of >50% drop in 24 hour urine albumin. The
minor response consisted of a dramatic improvement of painful
peripheral neuropathy resulting in an improvement of
performance status (ECOG PS 2 to PS0). Eight patients have
progressed and seven have died. With a median follow-up of 23
months in surviving patients, the median time to progression is
9.4 months (95% CI: 7.1 - not yet reached). Five patients have
remained progression free for > 24 months (42+, 25+, 43+, 25+,
24+ months).
Conclusions: DC vaccination with idiotype is clinically feasible
and safe. Early clinical results appear promising.
412
VACCINATION IN MULTIPLE MYELOMA PATIENTS:
LACK OF RESPONSE IN ADVANCED AND
REFRACTORY PATIENTS.
I.Clement Corral, N.Meuleman, I. Ahmad, C.Dedobbeleer,
Ph Martiat, D.Bron
Service de médecine interne, Institut J. Bordet, ULB, Brussel,
Belgium.
Background: Patients (pts) with multiple myeloma are at high
risk of infectious complications and vaccination against
Streptococcus pneumoniae is usually recommended. Response to
vaccine is known to be low in this population. However some
studies using idiotype vaccination after high dose chemotherapy
reported immune responses. We thus evaluated prospectively the
immune status against Clostridium tetani and Streptococcus
pneumoniae in pts with MM. We also evaluated the antibody
responses after vaccination against S.Pneumoniae in pts who
have no protective level antibody.
Material and methods: 27 pts were included. Serum was analysed
for antibody levels against S. pneumoniae and C. tetani in all pts.
For pts with no or weak level of antibody, vaccination was
performed and responses to vaccination was evaluated by the
increase of antibody level after 4-6 weeks. We stratified this
population into 2 groups: pts who had ≤ 2 different line (n=14) of
therapy and a group with more than two previous treatments
(n=13)°.
Results: there were 18 men and 9 women. The median age was
64 years (49-88). All pts had a protective titre against C.tetani
and vaccination was not required. Four pts (%) had a weak but
protective level of antibodies against S. pneumoniae before
vaccination. 24 pts were evaluable for their responses to
vaccination.
Results: in the group with ≤2 lines of treatment: 11 (92%) pts
increase their level of antibody to a protective level of antibody
and one pt (8%) failed to response to vaccination. In the heavily
treated group 8 pts (73%) have no or insufficient response to
vaccine and 3pts (27%) responded to vaccination. The rate of
efficiency responses to vaccine was thus significantly lower in
the heavy treated group compared to the other group (p=0.0028,
RR=0.141). No refractory pts response to vaccination. Four pts
lose their protective level against S.Pneumonie less than 2 years
after the vaccination.
Conclusion: although our series is too small to draw conclusion,
it suggest that pts with multiple myeloma have a weak protection
against S.Pneumoniae. The covering for Tetanos in this
population is still sufficient without a new vaccination. Response
to vaccination is strongly influenced by the number of
administrated treatment. Some patients lose prematurely their
protection and need of earlier vaccination than every 5 years
should be envisaged. Response to immunotherapeutique
strategies is likely to be better in patient in the early phases of
their disease and is probably ineffective
413
Immune responses to tetanus vaccination in myeloma
patients post autologous transplantation provide
information on timing of vaccine-based immunotherapy
McNicholl FP, McCarthy H, Ottensmeier CH, Duncombe
AS, Orchard KH, Hamblin TH, Smith AG, Stevenson FK
University of Southampton, Southampton, UK
Autologous stem cell transplantation (ASCT) with high-dose
melphalan conditioning prolongs survival in myeloma patients.
However, most patients eventually relapse and die from residual
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