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Multiple myeloma cells express a number of surface molecules capable of activating downstream anti-apoptotic signaling pathways which could favor their growth and survival. Such cell surface molecules have been considered to be prognostic factors for multiple myeloma (MM), as detailed in the following review, and, we speculate, may become possible therapeutic targets in the future.

5321 OBJECTIVES: Granulocyte colony-stimulating factors (G-CSFs) are widely used to accelerate haematopoietic recovery after bone marrow transplantation (BMT). Regulatory approval of biosimilar G-CSFs in Europe has been on the basis of comparable efficacy, safety and quality as the originator product. However, data are not presently available for all G-CSF clinical settings. This is the first reported use of a biosimilar G-CSF for neutrophil recovery after BMT. METHODS: A total of 23 consecutive patients (12 male, 11 female; mean ± SD age 47 ± 13 years) with haematological malignancy (multiple myeloma, n=12; Hodgkin’s lymphoma, n=6; non-Hodgkin’s lymphoma, n=4; acute myeloid leukaemia, n=1) were recruited at a single-centre. Nineteen patients were receiving their first BMT while it was the second autograft for 4 patients. Mobilisation chemotherapy consisted of high-dose (HD) VEP (n=14), ESHAP (n=4), HD Ara-C (n=3), HD cyclophosphamide (n=2) or ICE (n=1). Patients received biosimilar G-CSF (EP-2006, Sandoz Biopharmaceuticals) after myeloablative chemotherapy (primarily BEAM or melphalan 140/200 mg/m2 +/− bortozemib) with or without radiotherapy followed by autologous BMT. G-CSF therapy was started when absolute neutrophil count (ANC) was <0.5 × 109/l and was continued until ANC reached >1.5 × 109/l for 3 consecutive days. Response was evaluated after BMT using International Uniform Response Criteria. RESULTS: Mean ± SD number of CD34+ cells collected before transplantation was 10.1 ± 4.0 x106/kg/body weight. After BMT, one patient had a stringent complete response (CR), 7 patients had a CR, one patient a near CR, one patient a very good partial response (PR), 12 patients a PR, and one patient had progressive disease (overall response 96%). Mean recovery to ANC >0.5 × 109/l was 13.0 ± 4.0 days. Mean duration until platelet recovery >20 000/ml was 16.1 ± 4.4 days (not achieved in 5 patients at last available assessment). Mean duration of treatment with biosimilar G-CSF was 14.4 ± 5.1 days (range 6−23). Patients required antibiotics on a median of 4 days (range 1−6). Five patients (22%) experienced neutropenic events (neutropenic fever, n=4 and neutropenic enterocolitis and sepsis, n=1). Mean number of days in hospital was 28 ± 6. CONCLUSION: Biosimilar G-CSF appears to be effective in reducing the duration of neutropenia in patients undergoing myeloablative therapy followed by autologous BMT. The use of biosimilar G-CSFs may result in cost savings in cancer supportive care budgets. Disclosures: Dmoszynska: Mundipharma: Advisory Board; Roche: Honoraria.

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Introduction. Refractory Acute Myeloid Leukemia (AML) is associated with very bad prognosis. One of the major reason of induction chemotherapy failure is the expression of genes and proteins responsible for multidrug resistance (Multidrug Resistance 1 - MDR1, Multidrug Resistance-Related Protein 1 - MRP1, Breast Cancer Resistance Protein-BCRP, Lung Cancer Related Protein - LRP) and apoptosis (IAP-family genes: XIAP, cIAP1, cIAP2, survivin). The aim of the study was the evaluation of the influence of MDR and IAP-family genes expression on results of chemotherapy in patients (pts) with AML. Material and methods. The study was performed in 45 pts (20 females and 25 males; ranged from 18 to 82 years - mean 51.2) with newly diagnosed AML. There were following types acc. FAB classification: M0–1, M1–5, M2–13, M3–4, M4–16, M5–6 and cytogenetic risk groups: favorable-8, intermediate-29 and unfavorable-8 pts. The genes expression in leukemic cells was detected by RT-PCR method. All pts were treated with induction and consolidation therapy acc. Polish Adult Leukemia Group (PALG). Results. The expression of MDR1 gene was detected in 47%, MRP1 in 21%, BCRP in 10%, LRP in 26% and IAP-family genes in 78% of pts. Expression of MDR1 was significantly higher in M5 (p=0.02), but expression of cIAP1 and cIAP2 in M4 type (p=0.01). There was significant difference in MDR1 expression between unfavorable and good risk cytogenetic group (p=0.03), but there was none difference between cytogenetic groups in expression of IAP-family genes. There was significant difference in MDR1 expression between pts who achieved complete remission (CR) and pts without CR (p=0.01). When the expression of MDR1 gene was associated with the expression of BCRP and LRP, CR was never obtained. In all pts with complex genetic changes (MDR1+MRP1, MDR1+BCRP+LRP, MDR1+MRP1+BCRP+LRP) CR after one course of induction chemoterapy was not obtained. There was significant difference between CR rate after one course of chemotherapy in pts without MDR genes expression or expression only one gene and in pts with expression of two or more genes (p=0.02). There was no correlation between IAP-family genes expression and CR rate. Despite of differences in post-consolidation therapy (bone marrow transplantation in some pts) expression of MDR1 and survivin genes correlated with overall surival rate (p=0.05 and 0.03, respectively). Conclusions. Results of our studies on expression of MDR and IAP-family genes in pts with AML showed that expression of MDR genes better predicted response on induction chemotherapy than IAP genes. After confirmation on larger group of pts these findings may have important significance in defining of prognosis in AML and individualization of induction and postremission therapy, eventually with new generation of MDR modulators.

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