ALBERT

Beschreibung: Abstract 4157 In spite of the progress in the therapy of advanced stage classic Hodgkin lymphoma (cHL), still a significant proportion of patients fail to respond or relapse after complete remission. MicroRNAs (miRNA) are essential regulators of cell differentiation, emerging as robust predictor and prognostic markers. Specific miRNA signatures from the Hodgkin and Reed Sternberg cells (HRS) cells and their microenvironment have been proposed, but the potential prognostic role of them remains unclear. Here, we investigated whether miRNA signatures can allow to a better understanding of cHL pathogenesis and being applied in patient outcome prognostication.We have used mirRNA gene expression data from 32 samples of advanced cHL patients and 5 cHL derived cell lines (L540, L1236, L428, HDLM2, and KHMZ) to identify specific miRNA profiles from the tumoral cells and their non-tumoral microenvironment. A miRNA signature was identified in the cHL cell lines, probably reflecting functional properties of the HRS, whereas the others informed from properties of the reactive infiltrate. Selected miRNAs were further validated by performing laser capture microdissection using frozen samples in order to look for specific miRNAS preferentially expressed for either HRS cells and their surrounding microenvironment. In addition, logistic regression and Cox analysis allowed us to identify a set of 102 miRNAs differentially expressed (p

Beschreibung: Abstract 5049 Background. Treatment of frail or elderly patients with relapsing symptomatic/active Multiple Myeloma (MM) is very difficult due to concomitant diseases, impaired bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. Dexamethasone and new agents (thalidomide, lenalidomide, bortezomib and bendamustine) have been used in this setting, in most cases with doses adapted to the clinical situation. Aims. To retrospectively analyze the management of frail and/or very elderly MM patients with relapsed and active disease treated with reduced doses of the aforementioned agents in five hospitals in Madrid, Spain. Methods. The files of this group of MM patients were studied. The most common treatment has been the combination of low doses of lenalidomide (len) and of dexamethasone (dex), whereas treatment with reduced doses of other agents has been anecdotal; therefore we analyzed the results of len/dex combinations. Len and dex have been used in lower than standard doses, adapted to the individual initial situation of the patients and tailored according to effect and toxicity throughout treatment. There was no specific protocol and the management of the patients has depended exclusively on the practice and criteria of the treating physicians. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. The study has been approved by the Ethics Committee of Hospital Ramon y Cajal, as coordinating center. Results. 38 patients were included in the study. Mean age was 79 years (range 68–90). 30 pts (79%) were older than 75 years and 10 pts had over 85 years. More than half of the patients (21) had two or more comorbidities. Patients had previously received 1 to 5 (m=1. 8) different treatment modalities, including steroids, melphalan (25), bortezomib (20), thalidomide (6) (or their combinations), and others or even APBSCT (3). 23 pts (60%) had IgG (m=4087 mg/dl, range 868–13000); 13 (34%) IgA (m=2115, range 355–4930) and 2 (5%) only light chains. 22 had κ and 15 λ light chains. 19 (50%) had BJ proteinuria. Mean Hemoglobin level was 10. 7 gr/dl (7. 5–14. 1) and mean creatinine level 1. 3 mg/dl (0. 4–12. 9); 28 (74%) had bone disease. 3 pts had S&D stage I, 22 stage II, and another 13 stage III. 13 pts had ISS stage I, 17 had stage II and 7 stage III. Patients received between 1 and 30 cycles of len/dex (m= 8). Median initial Len dose was 10 mg, the majority between 5 and 15mg, although 4 received 25 mg that were rapidly reduced. Mean initial dex dose was 20mg/day for 4 days. 4 pts (10. 5%) achieved Complete Remission (CR) (3 with negative IF), 27 (71%) Partial Remission (PR) (5 with VGPR) and 2 (5%) a significant, but lesser than 50%, reduction of the M-component (Stable Disease, Std). Altogether, overall response (CR+PR+Std) occurred in 33 pts (86%). The best response occurred after 2 to 9 cycles (m=4) of len/dex. Treatment was stopped in 15 patients due to neurological (4) or hematological (1) toxicity, pulmonary embolism (1), unrelated causes (4) and after achieving a plateau response (5). Time to next treatment was 1–30 months, (m=8 mo). 7 pts relapsed after 3–21 months (m=7). 10 patients died, 5 of related (disease progression, cardiac amyloidosis, renal progression to ESRF) and 5 of unrelated (cancer, sepsis, myocardial infarction, congestive heart failure) causes. Grade III-IV bone marrow toxicity occurred in 9 pts and neurological toxicity (PNP) in 5 (all of them had previously been treated with bortezomib or thalidomide). Conclusions. Personalized low doses of len/dex have been the most common treatment for frail/very elderly patients with relapsed MM in our centers and it is an active and tolerable option in this setting. The haematological toxicity was expectable and manageable, but prior treatments with bortezomib or thalidomide were associated with limiting neurotoxicity. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Abstract 4950 Background & Aims The management of elderly patients with Multiple Myeloma (MM) previously treated requiring further therapy (although in most cases palliative) is very difficult due to the presence of concomitant diseases, decreased bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. As in this setting the tolerability of standard doses of conventional chemotherapy, high doses of dexamethasone or IMiDs is a concern, we report the preliminary results of the combination of tailored low doses of lenalidomide (len) and low doses of dexamethasone (dex). Methods We retrospective analyze the results of the combination of low dose lenalidomide and low dose of dexamethasone (len/dex) in 14 patients aged over 70 years with pretreated MM and progressive disease. Low doses of len (5-10 mg daily for 21days) were initially given and flexibly modified in subsequent cycles according to response and toxicity, along with low doses of dex (20-40 mg/day for 4 days) in most (12) patients. G-CSF and red cell transfusions were used when needed. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. Results Median age was 80 years (70-90). All patients had received between 2-5 different previous modality treatments (m=2), including bortezomib (7), thalidomide (4) or PBSCT (2). 11 pts had IgG, m=3397mg/dl (868-4990), 2 IgA m=1460 (1050-1870) and another one BJ. 9 pts had κ and 4 » light chains. Median Hemoglobin level was 10 gr/dl (7.2-11.4) and median creatinine level 1.19 mg/dl (0.75-1.63). 11 (78%) had bone disease. 9 pts had S&D stage II, 4 stage III and another one stage I. 7 pts had ISS stage II, 4 had stage I and 2 stage III. Patients received between 2 and 13 cycles of len/dex (m=6.8). 11 pts (78%) achieved Partial Remission (PR) and 2 (14%) achieved significant, but lesser that 50%, reduction of the M-component (Stable Disease: Std). Overall response (PR+Std) occurred in 13/14 patients (92.8%). The best response occurred between 2-12 cycles of len/dex. Grade III-IV bone marrow toxicity occurred in 5 pts (35 %) and neurological toxicity (PNP) in 5 pts (35%) (all of them had received previous bortezomib or thalidomide). Treatment was stopped in 6 pts: for unrelated causes (1), due to neurological (3) or haematological (1) toxicity and in 2 pts after achieving Std and both relapsed after 3 months. Conclusions Treatment with tailored low doses of lenalidomide and low doses of dexamethasone (len/dex) is an active and tolerable option for previously treated elderly patients with symptomatic MM. Low lenalidomide doses can be flexibly modified according to the quality of the response and the hematological toxicity that is expectable and manageable. Previous treatments with bortezomib or thalidomide is associated with neurotoxicity. Disclosures No relevant conflicts of interest to declare.