Haematologica 2003 - Supplements

esponse was 8 (2 – 12) months. To date, 4 patients are alive: 3
with stable MM and 1 with progressive disease. The median
overall survival was 8 months (1 – 16).
We have analysed the clinical pattern of relapsed/progressed
disease in our series. Out of the 7 relapses, 3 cases presented
untested and very extended pulmonary (2) and frontal bone (1)
plasmocytomas.
The remaining 4 patients presented progressive increase of
paraprotein levels associated with plasmacytic BM infiltration
and new osteolytic lesions. The extramedullary manifestation
were treated with radiotherapy and in all relapsers a weekly dose
(500 mg) of cyclofosphamide was added to the current therapy.
All relapsers died after 2 (1 – 3) months.
Out of the 5 patient with disease progression, 4 presented the
typical haematological features and 1 a large plasmacytoma,
extended from the 5th lumbar spine to the iliac region. This
patient, alive from 15 months, received radiotherapy, weekly
cyclofosphamide and regular courses of dex, as above reported,
achieving a partial control of disease, lasting from 5 months.
Median survival after progression was 2 (1 – 15) months.
Although the small number of patients, the occurrence of
extramedullary disease, found in 4/12 (33%) patients, suggests a
role of a resistant and more aggressive clone, who has lacked the
regulatory adhesion molecule-mediated mechanisms, causing
metastasis to distant sites, as the lung, maybe favoured by its fine
microcirculation.
Our experience, outlining the poor prognosis of the
relapsed/progressed MM patients receiving the reported salvage
therapy, suggests the need of further studies on the efficacy of
new drugs in modifying the clinical history of the advanced MM.
337
The combination therapy of thalidomide, incadronate
and dexamethasone (TID) for relapsed or refractory
multiple myeloma
Naoya Ochiai *1, Ryo Uchida *1, Shin-ichi Fuchida *1,
Akira Okano *1, Mayumi Hatsuse *2, Masashi Okamoto *1,
Eishi Ashihara *1, Tohru Inaba *1, Naohisa Fujita *1,
Masao Nakagawa *1 and Chihiro Shimazaki *1
*1: Second Department of Medicine, Kyoto Prefectural University
of Medicine, Japan; *2: Syakaihoken Kyoto Hospital, Kyoto, Japan
Introduction: Thalidomide has proven to be a useful drug for
treatment of refractory and relapsed MM patients and the efficacy
has been reported up to 35% in several clinical trials.
Thalidomide has been reported to restore the sensitivity of
myeloma cells to other drugs and to enhance the anti-myeloma
activity of dexamethasone, and in clinical study the combination
of thalidomide with dexamethasone have been more effective
than thalidomide alone. It is reported that nitrogen-containing
bisphosphonates, such as incadronate, have direct anti-myeloma
effect, and inhibit the mevalonate pathway and prevent posttranslational
prenylation of GTP-binding proteins for example
Ras. Based on these observations, we investigated the
combination effect of thalidomide, incadronate and
dexamethasone (TID therapy) as clinical phase 2 trial for relapsed
or refractory MM patients, in order to assess its efficacy and
toxicity.
Patients and methods: Nine patients with relapsed or refractory
MM were treated after informed consent was obtained from
patients. The protocol scheduled the administration of
thalidomide at doses from 100mg to 300mg/day, incadronate at
10mg/day iv weekly and dexamethasone at 12mg/day four days
every three weeks. Patients’ median age was 69 years (range: 52
to 75 years) and five were male. In myeloma subtypes, five were
IgG, two were IgA and two were Bence Johnes protein type. All
of patients were relapsing despite combination chemotherapy
contained high dose dexamethasone and two or more treatment
regimens were administrated before therapy. One patient was
highly aggressive relapsed after tandem auotologous peripheral
blood stem cell transplantation.
Results: All of nine patients achieved over 25% reduction of M-
protein after 1 cycle of TID therapy but in two patients it was
stopped because of severe somnolence. Of seven patients
evaluable for response after 3 cycles of therapy, five patients
achieved 50% reduction, one patient 25% reduction of M-protein
and one patient progressive disease. Toxicities TID therapy was
equally effective in patients with or without prior-resistance to
dexamethasone-based regimens. These data suggest that TID is a
feasible and promising therapeutic approach for advanced
multiple myeloma patients.
338
Clarithromycin, Dexamethasone and low dose
Thalidomide (CDT) is effective therapy in
relapsed/refractory myeloma; a Phase II study and
quality of life survey.
TCM Morris, DR Hull**, C Boyd**, FCG Jones, PJ Kettle, M
Drake, R McLoughlin*, J Quinn*.
Haematology Department, Belfast City Hospital, *Clinical Trials
Unit, Belfast City Hospital, Haematology Department, **Craigavon,
Area Hospital, Northern Ireland.
We have previously shown that Clarithromycin has a modest anti
myeloma effect1 and more recently a combination of
Clarithromycin, Dexamethasone and Thalidomide has been shown
to have significant activity in patients with myeloma2. We report a
very high response rate in a phase II trial of this combination in
which the object was to minimise the doses of both Thalidomide
and Dexamethasone. Sixteen patients (10 M, 6 F) with relapsed
(12) or refractory (4) myeloma, age range 52 – 83, from whom
informed consent was obtained, were given Clarithromycin 250mg
bd continuously, Dexamethasone 10 mg daily for 4 days, once
every 4 weeks and Thalidomide 50 mg nocte. An additional 4 days
of 10 mg of Dexamethasone was given on days 15–18 only. Dose
escalation of Thalidomide to 200mg by 50mg increments was
permitted but only 3 patients reached 150mg and 3 patients 100mg.
All patients received IV bisphosphonates once every four weeks.
Results: Three patients had complete remission, 2 very good
partial response, 8 partial response and 2 minimal response and
there was one non responder whose paraprotein fall failed to reach
the criteria for minimal response. The median response duration is
25 weeks. The median overall survival has not been reached but is
greater than 9 months. Most patients had one or more cytopenia at
the onset of therapy. Eight patients had thrombocytopenia (median
89 x 109/l, range 14-134); all had significant rises in the platelet
count, 7 to normal levels. Seven of 11 patients with anaemia had
haemoglobin increments of >1 g/dl, 5 reaching normal levels; of 7
patients with neutropenia