Background: Thalidomide can directly inhibit the growth and survival of myeloma cells. It also targets marrow stromal cells, alters IL-6 and TNF-a production and decreases adhesion of myeloma plasma cells .Due to modified cell –to- cell contacts and interactions within bone marrow microenvironment, malignant  plasma cells may become resistant to therapy and may develop tendency to disseminate and infiltrate other tissues in the periphery. The aim of study was to assess thalidomide treatment efficacy and pay attention to appearance of severe, especially cardiac, complications  and possibility of development of extramedullary myeloma manifestation following thalidomide therapy.

 Methods: We enrolled 21 patients (8 females and 13 males, aged 47- 78 years) with refractory/relapsed multiple myeloma who have failed at least one prior line of treatment. The time since myeloma diagnosis to onset of thalidomide therapy ranged from 7 to 120 months. In 10 patients thalidomide alone at doses from 100 to 400 mg/day was applied as  long-term therapy, in 3 thalidomide was given together with high-dose dexamethasone pulses, in 7 patients in form of combined treatment  with melphalan and prednison (MPT program) and in one- together with cyclophosphamide and dexamethasone (CTD program) .

Results: Of 10 patients treated with thalidomide only, partial remission was achieved in 2 patients, disease stabilization in one, and in 4 patients  disease progressed, including one in whom myeloma evolved into plasma cell leukemia.  Time to disease progression since the onset of thalidomide therapy ranged from 5 to 10 months.  In 3 patients the  treatment was interrupted due to adverse events: Morgagni-Adams-Stokes-syndrome, bradyarrhythmia- atrial fibrillation, sudden loss of hearing  and enormous  debilitation, respectively. In 3 patients, in whom thalidomide was administered together with high-dose dexamethasone, partial remission was achieved after two months of treatment. In one of those patients partial remission lasted 10 months but the treatment had to be stopped due to bradycardia while in two remaining patients partial remission lasted 3 months and ended with plasma cell leukemia in one patient, and  with plasma cell infiltration of lymph nodes in the other one.  In all assessed patients treated according to MPT or CTD regimens a partial response was achieved. In this group, the treatment was stopped in two patients; in one due to extensive skin lesions, and in the other one due to atrial fibrillation recurrences.

Conclusions: In relapsed/refractory myeloma the rate of response to thalidomide alone is 28%, with median  duration of response of 6 months. Our findings suggest that thalidomide is effective in initially reducing more mature plasma cell compartment confined to the marrow and allows a relatively immature myeloma cell compartment to escape marrow microenvironment. In one third of patients treatment with thalidomide is interrupted due to adverse events.

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2. EFFICACY AND SAFETY OF BORTEZOMIB (VELCADE) IN THE TREATMENT OF RELAPSED MULTIPLE MYELOMA
3. INCIDENCE OF JAW OSTEONECROSIS IN MYELOMA PATIENTS TREATED WITH BISPHOSPHONATES