ALBERT

Beschreibung: Background. Lenalidomide plus Dexamethasone is approved at first relapse and beyond in Europe, and has transformed the prognosis of Myeloma in the relapse setting. Lenalidomide plus Dexamethasone is approved until progression, that could last for years, the median PFS in phase 3 studies being at 17 months at first relapse, but many patients eventually reach 5 to 7 years these days. Dexamethasone was showed to enhance lenalidomide-antitumor efficacy and to prolong the progression-free survival. However, long term exposure to dexamethasone is also known to be associated to an array of adverse events. Finally, IMiDs are known to act through immunomodulation a class-based mechanism. It is possible that lenalidomide might show efficacy on the long run without need to dexamethasone use, at least for some patients with myeloma. We sought to study the impact of dexamethasone discontinuation beyond six months and one year, and compare this analysis to patients treated on lenalidomide plus dexamethasone. Method. We have recruited 200 relapse refractory myeloma patients for this study from various IFM centers. The patients were to be older than 18 years old and treated with lenalidomide plus dexamethasone. We sought to study the impact of the various ways to use dexamethasone in the real life, and therefore dexamethasone was given according to physician decision. We identified groups according to dexamethasone given high dose (4 days 160mg total in a raw), given once a week at 40mg (considered standard dose), given at lower dose (considered low dose) and a group that had dexamethasone discontinued. Patients were not allowed to have other type of combination but lenalidomide plus dexamethasone. Result. A total of 200 patients were analyzed, median age of 57 years old (range 25-76). 17,5% patients had renal dysfunction at diagnosis. ISS was 2 for 20% and 3 for 20%. Approximately 10% had either del17p or t(4;14). 7% of patients had previous history of venous thrombosis before the treatment. Response rate, survival, including TTP, PFS, EFS and overall survival will be presented at ASH with updated follow-up. Conclusion. This study aims to investigate the importance of long run and exposure to Dexamethasone in the Lenalidomide-Dexamethasone regimen. We also wished to assess the optimal dose of dexamethasone that could be given to patients with prolonged exposure to lenalidomide plus dexamethasone. Disclosures Arnulf: Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. MACRO:millenium: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Leleu:LeoPharma: Honoraria; Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Chugai: Honoraria.

Beschreibung: Background. Pomalidomide in association with dexamethasone is approved for RRMM in 3rd line and beyond based on the MM-003 multicenter international phase 3 study that demonstrated greater efficacy for Pomalidomide plus dexamethasone over high dose dexamethasone. However, MM-003 mainly recruited advanced RRMM with a median of 5 prior lines. Few data is available regarding real life Pomalidomide-based treatment in 3rd and 4th line RRMM. The aim of this study was to study efficacy and safety of Pomalidomide-based treatment in 3rd and 4th line RRMM. Methods. We studied 108 consecutive RRMM treated with Pomalidomide-based treatment in 3rd and 4th line in a multicenter-based study. All assessment made according to IMWG. Results. The median age was 62.5 (range, 30-86), with 36% older than 65 years, sex ratio M/F 1.25 and ISS disease stage 2 or 3 in 58%. 100% were exposed to bortezomib and refractory to Lenalidomide. 52 patients (48%) had pomalidomide-based therapy as 3rd, and 56 (52%) as 4th line. 73% of patients received a double-based therapy (Pomalidomide plus Dexamethasone) and 27% received a triple based therapy (Pomalidomide, Cyclophosphamide and Dexamethasone). Overall ORR was 55%, with 20% ≥VGPR including 5% CR, and was not statistically different in 3rd versus 4th line, and with PCd versus Pd, although the former was always better. With a median f-up of 45 months, overall 77% and 49% had relapsed and died, respectively, with significantly less in benefit to combination and 3rd line compared to Pd and 4th line (p=0.020). The median PFS was 6 (CI95% 2.3;9.6) and 9 (5.5;12.5) months in 3rd and 4th line (p=0.04), and 6 (CI95% 2.8;9.2) and 12 (8.5;15.5) months in Pd and PCd (p=0.04), respectively. Interestingly, the estimated 3 years PFS for 3rd line and PCd was 34% and 32% respectively, greatly superior to 4th line and Pd, 13% and 18%, respectively. Similarly, the median OS from start of Pomalidomide was not reached in 3rd and in PCd lines versus 23months (5;49), (p=0.04), and 32 months (5;-) for 4th line and Pd use, respectively. Pomalidomide was never permanently discontinued for safety issues, but 30 (28% of patients had to reduced pomalidomide dose, 25% to N-1 that is 3mg/d and 3% at N-2 that is 2mg/d. Expectedly, more patients (increased by 10%) had to reduce pomalidomide dose in 4th line compared to 3rd line, although it was not statistically significant, but not with PCd versus Pd. Indeed Cyclophosphamide but not pomalidomide is reduced in modified in dose or scheme when facing safety issues. No patient died related to adverse events. AEs leading to pomalidomide-based modification in schema included hematological in 40% and non hematological AEs in 12% of patients. Overall, the most common adverse events grade 3 or 4 were neutropenia (22%), anemia (11%), thrombocytopenia (7%) and infectious disease (5%). Conclusion. Pomalidomide-based therapy demonstrates efficacy in the real life with a manageable safety profile. We demonstrate herein that early use and combination improves MM on pomalidomide in the real life. Further prospective studies are warranted to confirm this data on a larger MM population. Disclosures Hulin: Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Perrot:Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Celgene: Honoraria. Macro:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress. Laribi:Hospira: Other: Grant; Amgen: Other: Personal fees; Novartis: Other: Grant and personal fees; Gilead: Other: Personal fees; Roche: Other: Grant; Takeda: Other: Grant and personal fees; Sandoz: Other: Grant; Teva: Other: Grant. Leleu:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Beschreibung: Background. Thalidomide is one of the most prescribed regimens upfront in eNDMM, e.g. elderly myeloma, essentially as melphalan-prednisone-Thalidomide (MPT). Several options are offered at 1st and 2nd relapse to patients initially exposed to Thalidomide with either bortezomib or lenalidomide-based therapy. On the other hand, the second most prescribed drug in elderly myeloma upfront is Bortezomib, primarily as Bortezomib-melphalan-prednisone (VMP), the 2nd standard of care upfront in Multiple Myeloma (MM) ineligible for transplantation. Interestingly, lenalidomide is the drug of choice at first relapse in the vast majority of cases in most countries where lenalidomide is approved at first relapse and beyond. In this situation, it is likely that the patients would not receive thalidomide throughout the disease course of myeloma. We sought to analyse whether patients not exposed to thalidomide upfront, and that were solely exposed to the 2 drugs, bortezomib-based regimen and lenalidomide-based therapy would have a lower survival than patients exposed to all 3 drugs, e.g. thalidomide, lenaldiomide and bortezomib. Method. A total of 145 patients were recruited in this multicentric study, 46,2% were in the thalidomide upfront exposed arm and 53,8% had never been exposed to thalidomide. Patients were required to be aged ≥65 years, NDMM treated with either thalidomide upfront or never been exposed to thalidomide upfront or later in the myeloma disease course. If not exposed to thalidomide, the patients were to have received bortezomib upfront and lenalidomide first relapse or vice versa. In the thalidomide group, all patients had MPT initially for a median of 8 cycles (range 3 - 12), at a median dose of thalidomide of 100mg/day (50-200), with 11% dose reduction. In the non-exposed thalidomide group, all patients had bortezomib upfront, patients received Vd, VCd or VMP upfront; lenalidomide was then given at first relapse to all patients. The median dose administered of bortezomib was 1.3mg/m², for a median of 5 cycles (2-9). Results. Overall, the median age was 73 years (range, 65 - 85), with 35% aged 〉75. The M/F ratio was 1.1, 38% were ISS 3, the median b2m was 5.5mg/L, 26% had an ECOG score ≥ 2, 42% had renal insufficiency, 11% had elevated LDH, 8% presence of plasmacytoma, and 14% had adverse FISH (del17p, t(4;14) and or t(14;16)). There was no difference in patients' characteristics across studied groups, according to exposure or not to thalidomide. With a median follow-up of 5 years, 60% have died overall; 69% in the thalidomide exposed group versus 52% in the thalidomide non-exposed group (p=0.027). The median OS of thalidomide exposed patients was 55.7 months (46;65) versus 44 months (35;53) in the thalidomide non exposed patients (p=0.079). In the thalidomide exposed group, the median PFS of the thalidomide, bortezomib then lenalidomide lines were 27 months (24;30), 11 months (8;13) and 13 months (10;15). In the thalidomide non-exposed group, the median PFS of bortezomib then lenalidomide lines were 17 months (13;21) and 13 months (6;20). We then studied the survival of patients from onset of first relapse in the thalidomide exposed group, e.g. upon treatment with bortezomib, followed by lenalidomide at subsequent relapse, 22.5 months (10;34) compared to patients in the thalidomide non-exposed group that received bortezomib upfront and lenalidomide at first relapse, 44 months (35;53), p=0.005. Conclusion. Overall, thalidomide exposed versus non exposed groups had similar OS, while OS was significantly lower in the thalidomide exposed patients at first relapse onset versus in the thalidomide non exposed patients from diagnosis. This data seems to recommend use of bortezomib- and lenalidomide-based regimens as early as possible in the myeloma disease course, but not to abandon thalidomide. Study of the impact of thalidomide in the post bortezomib, lenalidomide and pomalidomide era might thus be important to study and optimize. Disclosures Karlin: Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Legros:BMS: Speakers Bureau; ARIAD: Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Garderet:Bristol-Myers Squibb: Consultancy. Hulin:Celgene Corporation: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Stoppa:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria. Moreau:Janssen: Other: Adboard; Novartis: Other: Adboard; Takeda: Other: Adboard; Amgen: Other: Adboard; Celgene: Honoraria, Other: Adboard. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Zweegman:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. MACRO:celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Terpos:Janssen: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Amgen: Honoraria, Research Funding. Leleu:LeoPharma: Honoraria; Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Chugai: Honoraria.