A Study of Lenalidomide Based Chemotherapy in Multiple Myeloma in Indian Population: Special Appraisal of Thromboembolic Risk.

Multiple myeloma is a plasma cell tumor which accounts for about 10% of hematological malignancies. In recent years some advances in the management of this malignancy have been achieved, especially the newer drugs like thalidomide, lenalidomide and bortezomib. Lenalidomde, a second generation immunomodulatory drug has been shown in various series to be a highly effective agent in management of newly diagnosed as well as relapsed cases of myeloma. The incidence of venous thromboembolism in patients of myeloma taking Lenalidomide – Dexamethasone therapy has been reported as high as 17 %. The risk of thromboembolism is to some extent determined by genetic predisposition of a population. There are no published reports from the Indian subcontinent addressing the incidence of venous thromboembolism in patients with newly diagnosed or relapsed multiple myeloma treated with Lenalidomide – Dexamethasone.

Forty one consecutive patients diagnosed at our centre with multiple myeloma either afresh (n=30) or relapsed on a previously different treatment regime (n=11), were studied between Oct2007 to Jul 2009. Diagnosis was based on serum electrophoresis and immunofixation, bone marrow plasmacytosis, and relevant tissue involvement. Patients were staged as per Durie Salmon system, and all our cases were found to be in stage 3 (3A = 34 cases, 3B = 7 cases). Detailed baseline clinical, haematological, and biochemical parameters were recorded. Colour Doppler flow imaging (CDFI) using a Philips 5000 imager of the lower limbs by an experienced radiologist was performed in all patients for DVT. D dimer using immunoturbidometric semi quantitative slide agglutination assay which measures fibrinogen equivalent units which is usually twice the actual D dimer value (<1.0 mcg/ml as normal cut off, 1.0 – 2.5 mcg/ml as indeterminate) was measured in all cases at diagnosis. All patients were started on therapy with Lenalidomide 25 mg a day for 21 consecutive days every month, with dose modification for renal insufficiency as per GFR. Dexamethasone 40 mg a day for first four days was given to all cases. Low dose aspirin 75 mg / d was used as thromboprophylaxis. Patients were followed up monthly with clinical, haematological and biochemical monitoring, specifically looking for any progression of myeloma parameters. Screening for occurrence of DVT was done using CDFI, D dimer, and thorough clinical examination at baseline and at one, three and six months interval from initiation of therapy.

We report an overall response of 95% (nCR + CR : 30%) in newly diagnosed cases of multiple myeloma and 81.8% (nCR + CR : 36%) in patients with thalidomide failure / intolerant group. The primary toxic effect of lenalidomide was haematological and was manageable with dose adjustment of lenalidomide and supportive care. D dimer levels were found to be in the range of 0.5 to 2.4 mcg/ml (mean = 1.46 mcg/ml). On detailed follow up for upto six months there was no episode of venous thromboembolism recorded in any of the patients. All patients were asymptomatic for DVT and CDFI of lower limbs was normal at all points of examination in all patients of myeloma, newly diagnosed or relapsed.

Lenalidomide – Dexamethasone therapy is a highly effective regime for treatment of newly diagnosed and relapsed myeloma patients. In our cohort of both relapsed and fresh cases (n=41), on thromboprophylaxis with 75 mg asprin, not a single case of DVT was documented, proving its safety profile for venous thromboembolism. Larger trials would however be required to ascertain the exact risk of thromboembolism in patients of myeloma taking this treatment regime.

No relevant conflicts of interest to declare.