PB2128 CLINICAL BENEFIT OF LONG-TERM DISEASE CONTROL WITH POMALIDOMIDE AND DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS
Authors: M. Parisi, A. Romano, E. Martino, V. Calafiore, U. Markovic, V. Leotta, R. Giubbolini, S. Leotta, N. L. Parrinello, F. Di Raimondo, C. Conticello
Journal: HemaSphere (2019)

Background: Pomalidomide was approved in Italy in 2015 to treat double refractory or relapsed multiple myeloma (RRMM) patients. Aims: We retrospectively analysed RRMM patients treated with pomalidomide and dexamethasone (PomaD) either in real life, or previously enrolled in an interventional (STRATUS, MM-010) or currently enrolled in an observational study (MM-015) to provide further insights on safety and tolerability and clinical efficacy. Methods Between July 2013 and June 2018, 76 RRMM patients (including 33 DRMM) received pomalidomide according to approved schedule. Median age was 63.5 years (range 43-83); median number of prior therapies was 3 (range 1-8). In 9 patients a third agent was added to increase the response: cyclophosphamide (50 mg per day for 10 days/cycle) in 2 fit patients or clarithromycin (500 mg bid for 21 days/cycle) in 7 frail patients. Patients received subcutaneous filgrastim as part of prophylaxis regimen when leukocytes count was ≤ 2.5 · 109/L and neutrophils count was ≤ 1.5 · 109/L Results: A median number of 6 (range 1-21) PomaD cycles were given. The regimen was well tolerated with grade 3-4 haematological and non-haematological adverse events in 37 (48%) and 25 (33%) patients respectively. Most frequent grade 3-4 non-haematological AEs were: infection (10, 13%), glucose metabolism alteration (6, 7%), sepsis (6, 8%), pneumonia (6, 8%), fatigue (3, 2%), diffuse erythema (3, 2%), thromboembolism complicated by pulmonary embolism (2, 2%). In presence of serious AE, pomalidomide was reduced (11, 14%) or discontinuated (18, 23%). All patients had a response to treatment within first two cycles. We maintained for 6 cycles a median leukocyte counts higher than 3.5 · 109/L and a median neutrophil count higher than> 1.5 · 109/L, with only 6 (11%) patients hospitalized for pneumonia and infectious disease. Pomalidomide was reduced only for haematological toxicity. Dose reduction and drop-off were the lowest rates compared to recently published series. The disease control rate (DCR = ≥ SD) was high (82%), with 44% overall response rate after 6 cycles. Best response were: complete remission (5%), very good partial remission (4%), partial remission (35%), minimal response (7%) stable disease (38%). No differences in response rate were due to reduced kidney function or presence of extra-medullary disease (EMD). After a median follow up of 19.6 months, median time to next treatment (TNT) was 9.4 months and overall survival (OS) was 25.3 months. Univariate analysis showed that double refractory patients, or who received more than three previous lines had shorter TNT (p < 0.001), while EMD, clearance creatinine < 50 ml/min or the type of last treatment (a regimen based on lenalidomide or bortezomib or conventional chemotherapy) did not have any impact on TNT or OS. Only the number of previous lines and achievement of at least PR within the first 6 cycles were predictors of OS (p < 0.005). Irrespective of the depth of response, patients with a disease control of at least 6 months, (N = 36, 47%) had prolonged TNT (16.5 vs 4.1 months, p = 0.0003) and OS (56.3 vs 23.3 months, p < 0.0001) Summary/Conclusion: Our findings indicate that maintaining a high WBC and neutrophil count makes Pd a safe regimen in real-life management of RRMM and it allows in many patients a disease control for more than 6 months that in turn is associated to long TNT and OS.