Abstracts of Clinical Meeting on 12-July-2002
A Study Of The Safety And Efficacy Of Oral Melphalan, Prednisolone And Thalidomide (MPT) In The Treatment Of Multiple Myeloma: A UK Myeloma Forum Pilot Study.
Heather Oakervee, Clinical Research Fellow and Jamie Cavenagh, Consultant Haematologist. St Bartholomew's and The Royal London Hospitals. London EC1A 7BE
Oral Melphalan and Prednisolone (MP) is standard treatment for older patients with myeloma and thalidomide (T) alone is effective in advanced disease. MPT in combination may therefore have increased efficacy.
Patients with de novo or advanced disease unfit for high dose therapy were entered into this pilot study assessing feasibility and toxicity. Melphalan 7mg/m2 and prednisolone 20mg bd were given for 4 days and repeated every 28 days until plateau. Thalidomide was commenced at 50mg daily increasing by 50mg every 2 weeks to 800mg or the maximum tolerated dose.
A total of 22 patients were entered: 13 de novo patients (5M; 8F) median age 73 (63-86) and 9 patients with advanced disease (7M; 2F) median age 61 (51-76). Response to treatment was classified as MR (25-50% reduction in M band), PR (>50% reduction) or CR (absent M band). Of the de novo patients 8 /13 responded (CR 1, PR 4, MR 3); 2 had stable disease but one of these had only received one course. There were 2 early deaths and one patient is not evaluable. Of the patients with advanced disease 4/9 responded (all PR) and 2 patients had stable disease (both received only one course); there were 2 early deaths (one progressive disease) and one patient was not evaluable.
Serious complications occurred in 7 patients: 3 PE/DVT (including 1 death), 4 renal failure (including 2 deaths), 3 septic episodes. T was discontinued in 3 patients because of neuropathy.
The study was closed early because of the rate of serious adverse events. Both renal failure and thromboembolism occurred early in treatment suggesting that the combination of T with MP in the presence of a high tumour burden is particularly toxic. The combination does however appear effective and toxicity might be reduced if treatment with T follows initial cytoreduction.
A Study Of The Safety And Efficacy Of Thalidomide Combined With Vincristine, Adriamycin And Dexamethasone (T-VAD) In The Treatment Of Younger Patients With Multiple Myeloma: A UK Myeloma Forum Pilot Study
Heather Oakervee, Clinical Research Fellow and Jamie Cavenagh, Consultant Haematologist. St Bartholomew's and The Royal London Hospitals. London EC1A 7BE
Thalidomide (T) alone is effective in advanced myeloma and is synergistic with dexamethasone. This pilot study assesses the feasibility of and outcome to T with VAD and the effect on stem cell (PBSC) harvest and subsequent high dose melphalan (HDM).
Newly diagnosed/relapsed patients suitable for HDM with PBSC support were recruited. An initial course of VAD (V 0.4mg/day, A 9mg/m2/day and D 40mg/day each on D 1-4) was administered. A PBSC harvest was performed using cyclophosphamide (C) 1.5mg/m2 and GCSF (D+4-12) priming with collection of PBSC on D+10-12. Patients then commenced T at a dose of 200mg/day, increasing to 400mg after 3 weeks if tolerated and VAD continued 3 weekly to 6 courses (maximum). Upon achieving maximal response, T was stopped and a second C-primed harvest performed. Patients then proceeded to melphalan 200 mg/m2 and methylprednisolone 2g (D0-+4) with PBSCT using the second PBSCH. T maintenance (50 mg increasing to 100 mg) was commenced following regeneration.
Twenty one patients (16M; 5F) median age 58 years (40-64) have been treated. 11 have received HDM & PBSCT to date; 8 T-VAD only and 2 VAD and C only. The overall response rates for those patients who have received T-VAD are 5 CR (absent M band); 5VGPR (>90% reduction in M band) 3 GPR (>75% reduction) and 1 death on commencing T-VAD from progressive disease. Of the patients who have received T-VAD and HDM the responses are CR 5; VGPR 1; GPR 3. Two patients died during autografting of respiratory sinsitial virus pneumonitis. Sixteen of 21 patients had stem cells successfully collected after the first dose of C (Median collection 4.9 x 106 CD34 cells/kg; range 2.9-19.2); 2 failed to mobilise and 3 patients did not undergo harvesting. At second mobilisation 10/13 patients had successful collections (median 4.405 x 106 CD34 cells/kg (range 3.04-8.24)) and 3 patients failed to mobilise (1 had previously failed and one heavily pretreated) Median time to neutrophil engraftment was 14 days (11-18) and to platelet engraftment 10 days (9-30; N=9). There have been 4 line related thromboses and 1 pulmonary embolism.
T-VAD appears effective as treatment of myeloma and the addition of thalidomide to VAD does not appear to prejudice PBSC harvesting or subsequent engraftment.