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Objectives Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs is important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. Methods This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. Results The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Conclusions Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile and AEs were well managed according to study protocols and established guidelines. This article is protected by copyright. All rights reserved.

TPS8072Background: Multiple myeloma (MM) plasma cells express programmed cell death ligand 1 (PD-L1). In preclinical studies, monoclonal antibodies (mAbs) directed against PD-L1 demonstrated antimy...

Background: The introduction of newer agents, such as lenalidomide (LEN) and bortezomib (BORT), has improved survival outcomes for pts with RRMM (Kumar et al Leukemia, 2014). However, overall survival (OS) in pts who have failed or progressed on treatment (Tx) with newer agents is short and there are few additional treatment options available (Kumar et al Leukemia, 2012). POM is a distinct immunomodulatory agent with tumoricidal and immunoregulatory effects approved in combination with DEX for the Tx of pts with RRMM in the US and EU with ≥ 2 prior Txs, including LEN and BORT. Pivotal trials with POM + LoDEX have demonstrated greater survival benefits when compared with high-dose DEX (MM-003; San Miguel et al Lancet Oncol, 2013) or POM alone (MM-002; Richardson et al Blood, 2014). The STRATUS trial (MM-010; ClinicalTrials.gov: NCT01712789; EudraCT: 2012-001888-78) is a single-arm, open-label, phase 3b study being conducted in 19 countries across Europe designed to further evaluate safety and efficacy of POM + LoDEX in RRMM. Here, we present an updated analysis of safety and efficacy. Methods: Pts with refractory or relapsed and refractory disease (progressive disease [PD] on or within 60 days of last prior Tx), Tx failure with BORT and LEN, and adequate prior alkylator therapy were eligible. Pts with the following laboratory values were excluded: absolute neutrophil count < 800/μL; platelets < 75,000 or < 30,000/μL for pts with < 50% or ≥ 50% of bone marrow nucleated cells as plasma cells, respectively; creatinine clearance < 45 mL/min; hemoglobin < 8 g/dL; and peripheral neuropathy (PN) grade (Gr) ≥ 2. POM 4 mg was administered days 1-21 of a 28-day cycle in combination with LoDEX 40 mg/day (20 mg for pts aged > 75 yrs) on days 1, 8, 15, and 22 until PD or unacceptable toxicity. Thromboprophylaxis was required for all pts.Follow up continued for subsequent Tx, OS, and second primary malignancy until 5 yrs post enrollment. Safety was the primary end point, and key secondary end points included overall response rate (ORR) (≥ partial response), duration of response (DOR), progression-free survival (PFS), OS, and POM exposure. Results: A total of 682 pts were enrolled. The median age was 66 yrs (range, 37-88 yrs), and the median time since diagnosis was 5.3 yrs (range, 0.5-28.1 yrs). Pts were heavily pretreated with a median of 5 prior regimens (range, 2-18). Most pts were refractory to LEN (96%), BORT (84%), or LEN and BORT (80%). As of May 4, 2015, the median follow up was 16.8 mos and the median duration of Tx was 4.9 mos. In the 676 pts receiving POM + LoDEX, the most frequent Gr 3/4 treatment-emergent adverse events (TEAEs) were hematologic events (neutropenia [49.7%], anemia [33.0%], and thrombocytopenia [24.1%]. The most common Gr 3/4 nonhematologic toxicities were pneumonia (12.9%), fatigue (5.9%), and hypercalcemia (5.0%). Incidences of Gr 3/4 venous thromboembolism (deep vein thrombosis and pulmonary embolism) and PN were low (1.6% and 1.5%, respectively). Dose reductions, interruptions, and discontinuations of POM due to TEAEs were required in 22.0%, 66.3%, and 6.1% of pts; respectively. The ORR was 32.6%, with 0.6%, 7.6%, and 24.3% of pts achieving a complete response, very good partial response, and partial response, respectively. The median DOR was 7.4 mos. Median PFS and OS were 4.6 mos and 11.9 mos, respectively (Figure). Conclusions: The updated safety and efficacy results of STRATUS, the largest study of POM + LoDEX in a heavily pretreated RRMM population, were in line with results from the pivotal trials demonstrating that POM + LoDEX is effective and well tolerated. This analysis confirms that POM + LoDEX is a standard of care for pts with RRMM. Disclosures Dimopoulos: Janssen: Honoraria; Janssen-Cilag: Honoraria; Genesis: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Onyx: Honoraria; Amgen: Honoraria. Palumbo:Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria; Novartis, Sanofi Aventis: Honoraria. Cavo:Janssen-Cilag, Celgene, Amgen, BMS: Honoraria. Delforge:Novartis: Honoraria; Celgene Corporation: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Weisel:Amgen: Consultancy, Honoraria, Other: Travel Support; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding; Novartis: Other: Travel Support; BMS: Consultancy, Honoraria, Other: Travel Support; Onyx: Consultancy, Honoraria; Noxxon: Consultancy. Di Raimondo:Celgene Corporation: Research Funding, Speakers Bureau. Simcock:Celgene Corporation: Employment. Miller:Celgene Corporation: Employment, Equity Ownership. Slaughter:Celgene Corporation: Employment, Equity Ownership. Peluso:Celgene Corporation: Employment. Sternas:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Moreau:Celgene: Honoraria, Other: Adboard; Amgen: Other: Adboard; Janssen: Honoraria, Other: Adboard; Takeda: Honoraria, Other: Adboard; Novartis: Honoraria, Other: Adboard.

Introduction: For pts with RRMM who have failed or progressed on treatment (Tx) with newer agents, such as lenalidomide (LEN) and bortezomib (BORT), there are few Tx options, and overall survival (OS) is short (Kumar et al, Leukemia, 2012). POM is a distinct immunomodulatory agent with tumoricidal and immunoregulatory effects, and POM + LoDEX is approved in the United States and European Union for the Tx of pts with RRMM who have had ≥ 2 prior Tx, including LEN and BORT. Tx with POM + LoDEX has shown statistically greater survival benefits than high-dose DEX (MM-003; San Miguel et al, Lancet Oncol, 2013) or POM alone (MM-002; Richardson et al, Blood, 2014). POM + LoDEX has also demonstrated high overall response rates in pts with RRMM in the STRATUS trial (MM-010), a single-arm, open-label phase 3b study being conducted in 19 countries across Europe with a primary endpoint of safety (Dimopoulos et al, EHA 2015). Italian pts constituted the largest national subset in MM-010; hence, this subanalysis examines the safety and efficacy of POM + LoDEX in pts from Italy. Patients and Methods: Pts with RRMM (progressive disease [PD] on or within 60 days of last prior Tx) who had experienced Tx failure with BORT and LEN and had received adequate prior alkylator therapy were eligible. Pts received POM 4 mg on days 1-21 of a 28-day cycle in combination with DEX 40 mg (20 mg for pts aged > 75 yrs) on days 1, 8, 15, and 22. Thromboprophylaxis was required for all pts, and Tx was continued until PD or unacceptable toxicity. Results: A total of 219 pts were enrolled in MM-010 in Italy. The median age of this patient population was 67.0 yrs (range, 42-84 yrs), and 54.8% of pts were male. The median time since diagnosis was 5.5 yrs, and 37.0% of pts were International Staging System stage III. Patients were heavily pretreated, with a median of 4 prior anti-myeloma regimens (range, 2-11), and most pts were refractory to LEN (95%), BORT (82.2%), or both LEN and BORT (78.1%). As of May 4, 2015, 2 pts (0.9%) were not treated, 54 pts (24.7%) were still on treatment, and 163 pts (74.4%) had discontinued. After a median follow-up of 11.3 mos, in the intention-to-treat population, the overall response rate was 37.9% (range, 31.4%-44.7%), the median duration of response was 6.8 mos (95% CI, 4.9-10.8 mos), progression-free survival (PFS) was 5.2 mos (95% CI, 4.4-6.4 mos), and OS was 12.0 mos (95% CI, 10.6-15.2 mos). The most frequent grade 3/4 treatment-emergent AEs were neutropenia (56.7%), anemia (25.8%), thrombocytopenia (23.5%), and pneumonia (12.4%). Incidence of grade 3/4 venous thromboembolism (deep vein thrombosis and pulmonary embolism) and peripheral neuropathy were infrequent (2.3% and 0%, respectively). The most common reasons for discontinuation were disease progression (49.8%), death (10.0%), and adverse events (AEs; 5.0%). AEs led to dose reductions or interruptions of POM in 23.0% and 71.0% of pts, respectively, and the median relative dose intensity for POM was 0.90. Conclusions: In line with previous studies, POM + LoDEX was active in Italian pts, a representative subset of the heavily pretreated MM-010 population. PFS and OS were consistent with those seen in previous trials. POM + LoDEX treatment was well tolerated, and discontinuations due to AEs were infrequent, consistent with the well-known toxicity profile and the appropriate drug management. This study confirms that POM + LoDEX is effective in patients with advanced RRMM, including those who have experienced failure of prior Tx with BORT and/or LEN. Disclosures Cavo: Janssen-Cilag, Celgene, Amgen, BMS: Honoraria. Petrini:Novartis: Research Funding; Celgene Corporation: Research Funding; Italfarmaco: Research Funding; Roche: Research Funding. Caravita di Toritto:Celgene Corporation: Honoraria, Research Funding. Offidani:Celgene, Janssen: Honoraria. Petrucci:Celgene Corporation: Honoraria; Janssen-Cilag: Honoraria; Amgen: Honoraria; Mundipharma: Honoraria; BMS: Honoraria. Rodeghiero:Celgene Corporation: Honoraria, Research Funding. Simcock:Celgene Corporation: Employment. Slaughter:Celgene Corporation: Employment, Equity Ownership. Herring:Celgene Corporation: Employment. Peluso:Celgene Corporation: Employment. Palumbo:Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria; Novartis, Sanofi Aventis: Honoraria.

Introduction: The introduction of newer agents, such as lenalidomide (LEN) and bortezomib (BORT), has resulted in improved survival outcomes in pts with RRMM (Kumar, Leukemia, 2012), and a greater depth of response has been associated with improved efficacy outcomes in RRMM (Harousseau, Haematologica, 2010). However, once pts become refractory to these newer agents, they experience poorer outcomes, with short overall survival (OS; Kumar, Leukemia, 2012). POM + LoDEX is approved for the treatment of pts with RRMM with ≥ 2 prior treatments, including LEN and BORT. A previous subanalysis of pts treated with POM + LoDEX in the MM-003 trial demonstrated that pts with a deeper response, as measured by a reduction in serum M protein, experienced longer OS and progression-free survival (PFS; San Miguel, ASH 2013). POM + LoDEX was shown to be safe and effective in the phase 3b STRATUS trial (MM-010; Dimopoulos, EHA 2015); here, we present the outcomes in this pt population by prior treatment and depth of response. Patients and Methods: Pts with RRMM (progressive disease [PD] on or within 60 days of last prior treatment) with prior adequate alkylator therapy in whom LEN and BORT treatment failed were eligible. POM 4 mg was administered on days 1 to 21 of a 28-day cycle in combination with LoDEX (40 or 20 mg for pts aged ≤ 75 or > 75 yrs, respectively) on days 1, 8, 15, and 22. Treatment was continued until PD or unacceptable toxicity, and thromboprophylaxis was required for all pts. For this efficacy analysis, pts were grouped according to prior treatment history or reduction in serum M protein level. Results: As of May 4, 2015, 682 pts were enrolled and 676 have received POM + LoDEX. In the intent-to-treat population, the median age was 66 yrs, 56% of pts were male, the median time since diagnosis was 5.3 yrs, and pts had received a median of 5 prior regimens. Approximately half of all pts (54.5%) had received prior thalidomide (THAL), and 186 vs 496 pts had received ≤ 3 vs > 3 prior regimens of therapy, respectively. Most pts were refractory to LEN (96%), BORT (84%), or both LEN and BORT (80%). The overall response rates (ORRs) were generally similar regardless of prior THAL, number of prior regimens, and LEN/BORT refractoriness. Pts who received prior THAL had an ORR of 30.4% compared with 35.2% for pts who did not receive prior THAL (Table). Similarly, for pts with a history of ≤ 3 vs > 3 prior antimyeloma regimens, ORR was 28.5% vs 34.1%. ORR did not appear to be impacted by refractory status to LEN and/or BORT (ORR, 32.1%-32.9%). PFS was comparable and independent of prior THAL exposure, number of prior regimens, and LEN/BORT refractoriness (PFS, 3.9-4.6 mos). Median OS was also similar for pts with or without prior THAL exposure (11.4 mos vs 12.0 mos, respectively), as was OS for pts with ≤ 3 vs > 3 prior regimens (12.8 mos vs 11.9 mos, respectively). Pts with LEN and/or BORT refractoriness had the same median OS of 11.9 mos. Analysis of PFS by serum M protein levels showed that a greater reduction in these levels was associated with a longer median PFS: for pts with a serum M protein reduction of < 25%, ≥ 25% to < 50%, and ≥ 50%, median PFS was 3.0, 4.8, and 7.6 mos, respectively. Conclusions: The efficacy of POM + LoDEX in this heavily pretreated population was independent of treatment history. ORR, OS, and PFS were not significantly impacted by treatment history with THAL, having ≥ 3 prior regimens, or refractoriness to LEN and/or BORT. As shown previously with POM + LoDEX, there was a clear trend toward prolonged PFS in pts with a greater reduction in serum M protein levels. This analysis supports POM + LoDEX as a standard of care for pts with RRMM. Figure 1. Figure 1. Disclosures Moreau: Celgene: Honoraria, Other: Adboard; Takeda: Other: Adboard; Janssen: Other: Adboard; Amgen: Other: Adboard; Novartis: Other: Adboard. Palumbo:Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria; Novartis, Sanofi Aventis: Honoraria. Cavo:Janssen-Cilag, Celgene, Amgen, BMS: Honoraria. Delforge:Novartis: Honoraria; Celgene Corporation: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Weisel:Amgen: Consultancy, Honoraria, Other: Travel Support; Noxxon: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Novartis: Other: Travel Support; Onyx: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Other: Travel Support. Knop:Celgene Corporation: Consultancy. de Arriba:MundiPharma: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Speakers Bureau. Simcock:Celgene Corporation: Employment. Miller:Celgene Corporation: Employment, Equity Ownership. Slaughter:Celgene Corporation: Employment, Equity Ownership. Watkins:Celgene Corporation: Employment. Herring:Celgene Corporation: Employment. Biyukov:Celgene: Employment, Equity Ownership. Peluso:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Dimopoulos:Amgen: Honoraria; Novartis: Honoraria; Genesis: Honoraria; Janssen-Cilag: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Onyx: Honoraria.

e264 at 1 mg/m , peripheral neuropathy of any grade(G) occured in 37,5%, G1 : 5 (15,6%) G2: 5 (15,6%) and G 3/4 : 2 (6,3 %) happening less commonly with subcutaneous infusion of Bortezomib. 08 patients had infectious pulmonary syndrome causing two deaths. 28 patients are alive: 04 pts in CR, 08 in VGPR and 10 in PR; 06 pts relapsed with median delay of 10 months (04-21). 07 pts died (21,9%) , one in CR, 4 after progression, one after severe neuropathy and one in VGPR after pulmonary infection. Anemia G4 seen in 3 pts (9,4%), Neutropenia G3 : 1 pt, Thrombocytopenia G2 : 3 pts. Other side effects included asthenia G2 and rarely diarrhea. Subcutaneous administration was locally very well tolerated. Median overall survival not reached; probability of survival 1⁄4 65 % at 16 months. Conclusion: In our practice, 41 % of patients are aged under 65 years; according to this observation, we can see that our population of myeloma is young and our results are encouraging; we hope soon to practice ASCT in our service to improve these results. 6. Multiple Myeloma Therapy Relapsed/Refractory Patients