Abstract: Introduction .Treatment of multiple myeloma (MM) patients (pts) has radically changed over the last years following the introduction of next generation proteasome inhibitors (PI) and immunomodulatory derivatives (IMiDs). Despite the improvement of pts' outcome due to these drugs, MM remainsan incurable disease given its propensity for clonal heterogeneity and its complex interaction with the surrounding bone marrow microenvironment. Almost all pts eventually relapse despite their responses to PI, IMiDs or both. Recently, one further therapeutic option for MM patients is represented bydaratumumab, an anti-CD38 monoclonal antibody approved alsofor heavily pre-treated pts who have exhausted all other therapeutic options. Patients and Methods. We report the experience of the Multiple Myeloma GIMEMA Lazio Group in 50 relapsed/refractory MM pts treated with daratumumab as monotherapy. Twenty-nine pts (58%) were men and 21 (32%) women. According to the ISS,24 pts (48%) were ISS I, 11 (22%) ISS II, 7 (14%) ISS III and 8(16%)not evaluable. According toDurie & Salmon, 20 pts (40%) were 1 A, 2 (4%) 1 B, 12 (24%) II A, 1 (2%) II B,7 (14%) III A, 3 (6%) III B and 5 (10%) not evaluable. Isotype IgG-k was found in 21 pts (42%), IgG-λ in 13 (26%), IgA-k in 6 (12%), IgA-λ in 3 (6%), micromolecular k in 5 (10%) andmicromolecular λ in 2 (4%). Median age was 62.3 years (range, 43.1 - 85.7); 32 pts (64%) were refractory to the last line of therapy; 26 (52%) had previously received a stem cell transplant (13 single autologous, 12 tandem autologous and one an autologous followed by an allogeneic transplant). After a median follow-up from diagnosis of 54.5 months (range 1.0 - 203.0) and a median of 3 previous lines of therapy (range 2 - 8), pts received a median of 3 cycles (range 1 - 23) of daratumumab. Results.Forty-seven pts (94%) performed at least one cycle and were evaluable for response. The overall response rate was 74%; in particular, 2 pts obtained a CR (4.2%), 3 pts a VGPR (6.3%), 17 pts a PR (36.2%) and 15 pts a SD (32%), while 10 pts (21.3%) presented a PD. After a median follow-up of 5.3 months (range 1 - 31) ,24 pts(65%) were still in response and alive, one pt (5.8%) died in PR due to post-allograft GVHD and 12 (32%) experienced a PD (1 CR, 1 VGPR, 6 PR and 4 SD). Seven (19%) pts died and 30 (81%) are still alive. With regard to the 3 pts not evaluable for response, 2 died early and 1 has not yet completed the first cycle. The median time to response, duration of response, progression-free survival and overall survival were 1.5 months (range 1.0 - 6.0), 6.7 months (95% CI, 4.14 - 14.21), 5.7 months (95% CI, 3.26 - 13.75) and 22.5 months (95% CI, 11.6 - 36.1), respectively. Daratumumab was well tolerated; the most common adverse events, of any grade, were infections in 20 pts (42.0%) and anaemia in 21 pts (44.0%), which did not lead to treatment discontinuation. Infusion-related reactionswere observed in 7pts (14.8%), grade I-II (4 pts), grade III (3 pts). Conclusions.Daratumumab monotherapy is an effective strategy for heavily pre-treated and refractory pts with multiple myeloma, with a favorable safety profile. This treatment option needs to be considered for pts not eligible for combination therapy of daratumumab with bortezomib or lenalidomide, recently approved also in our country. Disclosures Vozella: Takeda Oncology; Amgen: Honoraria. Annibali:Celgene; Takeda; Amgen, Janssen Cilag: Honoraria. Caravita di Toritto:Johnson & Johnson: Other: Advisory Board, Travel and Accomodation EHA; Amgen: Other: Advisory Board; Bristol-Myers Squibb: Honoraria, Other: Travel and Accomodation EMN; Takeda: Other: Advisory Board; Celgene: Other: Advisory Board, Travel and Accomodation ASH, Research Funding. Foà:NOVARTIS: Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; AMGEN: Other: ADVISORY BOARD; INCYTE: Other: ADVISORY BOARD; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau. Petrucci:Takeda Oncology; Amgen; Celgene; BMS; Janssen Cilag: Honoraria, Other: Advisory Board.

Abstract: Background. The overall survival (OS) of multiple myeloma (MM) patients (pts) has improved over the years due to the introduction of several novel drugs, such as proteosome inhibitors (PI), immunomodulatory drugs (IMiDs) and, more recently, anti-CD38 monoclonal antibodies (moAb). Nevertheless, the majority of pts continues to relapse, and MM remains an incurable disease. To date, no standard of care has been established for relapsed/refractory (RR) MM pts who have been exposed to the main anti-myeloma drugs. Currently, these pts have a limited number of available treatment options and represent an unmet medical need. Moreover, the outcome of pts failing standard of care regimens, which is now defined as triple-refractory (including PI, IMiDs and moAb), is poor, with a median progression free survival (PFS) of 3-4 months and OS of 8-9 months. Novel therapeutic strategies with different mechanisms of action are warranted to overcome the natural occurrence of relapse or therapy resistance in RR MM pts. Immunotherapy, especially T-cell based approaches, represents the emerging therapeutic strategy for this subset of pts. Chimeric antigen receptor (CAR)-modified T cells are a promising new therapy approach for triple refractory RRMM. Different constructs and specific CAR-T targets are being studied, but BCMA-directed CAR-T cells have so far provided the most convincing evidence of activity, with one product (idecabtage vicleucel) recently approved by FDA. Aims. The primary endpoint of this observational and retrospective study was to define the clinical characteristics and outcome of a cohort of RR MM pts potentially eligible to CAR-T cell treatment according to the KarMMa trial criteria 1. Secondary endpoints were aimed at defining specific factors influencing CAR-T cell therapy eligibility and at identifying a real-life estimate of RRMM pts truly eligible for CAR-T cells. Methods and Results. This is a cohort analysis that used electronic REDCap, a data capture tool hosted at the Sapienza University, on RRMM pts managed between January 2018 and July 2021 at 4 Italian Centers of the Multiple Myeloma GIMEMA Lazio Group. At the time of data collection, 47 RRMM pts had underwent at least 3 prior therapy regimens; they had received a previous PI, IMiDs and a moAb and were considered refractory to the last regimen. The clinical characteristics are listed in Table 1. Median age was 68 years (43-86), 27 (61%) pts were & gt;65 years; 27 (57%) were male. Of 47 pts, 33 (68%) were ECOG 0-1 and 14 (30%) were ECOG ³2; 21 pts (44%) were ISS III. The majority of pts, 28 (59%), had undergone an autologous stem cell transplantation; 31 pts (65%) had received 3 prior lines of therapy and 16 (34%) & gt;3 prior lines of therapy. Thirty-seven (78%) were triple-refractory and 8 (17%) were penta-refractory. Based on the KarMMa trial criteria, 22/47 pts (47%) would be defined as eligible and 25 (53%) not eligible for CAR-T cell therapy. Specifically, 14 (30%) pts were not eligible because of an ECOG ³2, 24 (62%) had an organ dysfunction such as impaired renal function (eGFR & lt;45 ml/min/1.73m 2), anemia and thrombocytopenia. Of the 25 pts considered ineligible for CAR-T cell therapy, 17 (68%) presented ≥2 ineligibility criteria. The entire cohort of 47 pts had a negative hepatitis and HIV serology, and no patient had previously undergone anti-BCMA therapy or an allogeneic stem cell transplantation. After a median follow-up of 34.7 months (mo) (0-53.8), the median OS for the entire cohort was 21.7 mo (95% CI: 14.2-36.9) (Fig. 1). The median OS was 30.7 mo (95%, CI: 14.21-NA) in eligible pts vs 16.2 mo (95%, CI: 6.28-NA) in non-eligible pts (p=0.002) (Fig.2). The median PFS of the entire cohort was 7.7 mo (95%, CI: 5.39-13.85) (Fig. 3) and the median PFS was 7.8 mo (95%, CI: 5.16-19.1) in eligible pts vs 6.5 mo (95%, CI: 3.36-NA) (p=0.513) in non-eligible pts (Fig.4). Conclusions. Despite the limits of a retrospective study and a limited cohort, our real-life analysis shows that heavily treated pts with RRMM are less likely to be eligible for CAR-T cell therapy. Considering the emergent role of quadruplet combined approaches for first-line therapy and given the therapeutic relevance of CAR-T cells for the management of RRMM pts previously exposed to PI, IMiDs and moAb, our data could help to better define pts who could benefit from CAR-T cells under the current indications, while waiting for an extension of this approach to earlier disease stages. 1. N Engl J Med 2021;384:705-16 Figure 1 Figure 1. Disclosures Fazio: Janseen: Honoraria. Caravita di Toritto: celgene: Other: travel expenses, Research Funding; Janseen: Other: travel expenses, Research Funding; amgen: Other: advisory board; takeda: Research Funding; GSK-SANOFI: Other: advisory board. Martelli: Gilead: Other: advisory board; Novartis: Other: advisory board. Petrucci: Janssen-Cilag: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board.

Abstract: Flow cytometry is a highly sensitive and specific approach for discriminating between normal and clonal plasma cells in multiple myeloma. Uniform response criteria after treatment have been established by the International Myeloma Working Group and the EuroFlow Group; however, the way in which flow cytometry data are reported has suffered from no collaborative or multicentre efforts. This study, involving 8 expert laboratories and 12 clinical hematology units of the Lazio region in Italy, aims to produce a uniform and shared report among the various Centres. From the pre-analytical phase to sample processing, data acquisition, analysis, and evaluation of the potential limitations and pitfalls of the entire process, the study reaches a final conclusion shared by laboratories and clinicians according to the most updated principles and recommendations. The aim was to identify the necessary data to be included in the clinical report by using multiple-choice questionnaires at every single stage of the process. An agreement of more than 75% of the laboratories was considered mandatory for the data to be included in the report. By ensuring the operational autonomy of each laboratory, this study provides a clear report that limits subjective interpretations and highlights possible bias in the process, better supporting clinical decision-making.

Abstract: INTRODUCTION: Twice weekly carfilzomib is approved at two different doses, 27 mg/m2 in combination with lenalidomide and dexamethasone, and 56 mg/m2 with dexamethasone, for the treatment of relapsed and/or refractory multiple myeloma (MM). To reduce the treatment burden, the phase 3 A.R.R.O.W. study compared once weekly (70 mg/m2) to twice weekly (27 mg/m2) carfilzomib in relapsed/refractory MM patients, showing that once weekly carfilzomib increased the overall response rate (ORR) and prolonged progression-free survival (PFS) as compared to the twice weekly schedule. Here we present a pooled analysis of two phase 1/2 studies to compare once vs. twice weekly carfilzomib in newly diagnosed (ND)MM patients. METHODS: Transplant ineligible, NDMM patients enrolled in the single-arm IST-CAR 561 and IST-CAR 506 studies were pooled together. All patients received 9 28-day induction cycles of carfilzomib, either 70 mg/m2 once weekly on days 1,8,15 (IST-CAR 561) or 36 mg/m2 twice weekly on days 1,2,8,9,15,16 (IST-CAR 506), combined with cyclophosphamide (300 mg/m2 on days 1,8,15) and dexamethasone (40 mg on days 1,8,15,22). After induction, patients received maintenance with single agent carfilzomib at the same dose and schedule as induction phase, administered until progressive disease or intolerable toxicity. The primary objective was to compare PFS and overall survival (OS) from induction and maintenance, responses and rates of adverse events (AEs) with once vs. twice weekly carfilzomib. RESULTS: 121 NDMM patients (63 from IST-CAR 561 and 58 from IST-CAR 506) were analyzed. Median age at diagnosis was 72 years (IQR 68-74 years); baseline characteristics, ISS, cytogenetics by FISH and frailty status according to the IMWG frailty score, were balanced between the two groups (Table 1). After a median follow-up of 39 months, in the overall population, median PFS, PFS-2 and OS from start of induction were 36 months, 49 months and NR, respectively. No difference was observed in terms of median PFS (35.7 vs. 35.5 months; p=0.26), PFS-2 (48.6 vs. 48.5; p=0.51) and OS (49 vs. NA months; p=0.50) between patients who received once vs. twice weekly carfilzomib, irrespective of age, ISS, FISH status and frailty score (Figure 1). At cycle 9, no significant difference in the rate of ≥ partial response (PR; 87% vs. 90%; p=0.78) and ≥ near complete response (nCR; 30% vs. 47%; p=0.09) was reported in the two groups. Furthermore, the rates of patients who reduced (13% vs. 24%) or discontinued carfilzomib (27% vs. 28%) were comparable in the once vs. twice weekly carfilzomib, as were the rates of ≥1 grade 3-4 hematological (24% vs. 27%) and non-hematological (30% vs. 32%) AEs. After the induction phase, 90 patients started carfilzomib maintenance, 47 in the once weekly group and 43 in the twice weekly group. Overall, median PFS from start of maintenance was 31 months, while median PFS-2 and OS were NR. At 3 years, no difference was observed in terms of PFS (47% vs. 51%; p=0.92), PFS-2 (65% vs. 74%; p=0.74) and OS (72% vs. 73%; p=0.71) between patients who received once vs. twice weekly carfilzomib, irrespective of age, ISS, FISH status, frailty score and best response at induction. Among patients who received maintenance, 17% of patients deepened their response. Similar rates of ≥nCR (49% vs. 60%, p=0.30) and ≥CR (30% vs. 37%; p=0.51) were observed between the once vs. twice weekly groups. During maintenance, 26% and 16% of patients required ≥1 dose reduction of carfilzomib in the once and twice weekly carfilzomib, while 27% and 30% of patients discontinued carfilzomib due to AEs or death, respectively. The rates of ≥1 grade 3-4 hematological (0% vs. 5%) and non-hematological (19% vs. 23%) AEs were comparable within the two groups. CONCLUSION: In patients with NDMM, once weekly carfilzomib at 70 mg/m2 and twice weekly carfilzomib at 36 mg/m2 combined with cyclophosphamide and dexamethasone compared favorably with current standard of treatment. Moreover, once weekly carfilzomib administered both in the induction and maintenance phase resulted in similar PFS, PFS-2 and OS as compared to a lower (36 mg/m2), twice weekly infusion. The once weekly schedule at 70 mg/m2 was well tolerated and did not increase the risk of dose reduction or discontinuation in comparison with the twice weekly schedule at 36 mg/m2. These data support the use of triplet regimen including once weekly schedule of carfilzomib as initial treatment of MM patients in future trials. Disclosures Bringhen: Celgene: Honoraria; Amgen: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; Takeda: Consultancy; Bristol-Myers Squibb: Honoraria. Petrucci:Bristol-Myers Squibb: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board. De Paoli:Gilead: Other: Advisory Board; Celgene: Other: Advisory Board; Amgen: Other: Advisory Board; Janssen: Other: Advisory Board. Musto:Amgen: Honoraria; BMS: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Offidani:Bristol-Myers Squibb: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board. Cavo:GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Caravita di Toritto:Johnson & Johnson: Other: Advisory Board, Travel and Accomodation EHA; Amgen: Other: Advisory Board; Bristol-Myers Squibb: Honoraria, Other: Travel and Accomodation EMN; Takeda: Other: Advisory Board; Celgene: Other: Advisory Board, Travel and Accomodation ASH, Research Funding. Montefusco:Janssen: Other: Advisory Board; Amgen: Other: Advisory Board; Celgene: Other: Advisory Board. Palumbo:Takeda: Employment. Boccadoro:Mundipharma: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Larocca:Janssen-Cilag: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria.

Abstract: Introduction: Bendamustine, a bifunctional alkylating agent, exerts a mechanism of action different from that of other conventional alkylators despite it remains mostly unknown. In patients with newly diagnosed or relapsed-refractory MM bendamustine has proven to be active either as monotherapy or in combination with new drugs, particularly bortezomib and immunomodulatory agents. Methods: The preliminary results of this prospective, phase II study conducted in 22 Italian centres are recently published (Blood Cancer J. 2013, 3: e162). Here we present the conclusive results of the combination Bendamustine (70 mg/m2 days 1, 8), Bortezomib (1.3 mg/ m2 days 1, 4, 8, 11) and Dexamethasone (20 mg days 1-2, 4-5, 8-9, 11-12) (BVD) administered every 4 weeks in patients with relapsed-refractory MM of any age, with adequate cardiac, liver and hematological function, not refractory to bortezomib and treated with no more than four previous lines of therapy. The primary endpoint of this study was achievement of a response at least PR, as to IMWG criteria, after four cycles of BVD. Patients achieving a response less than a PR were taken off-study. Patients obtaining at least a PR received two additional treatment cycles followed by a 12-months consolidation phase with cycles repeated every 2 months. Therefore, patients with a PR after the induction phase could receive up to 18 months of treatment and up to 12 cycles of BVD. Results: 75 patients were included in the study. Median age was 68 years (range 41-85 years), 26.5% had ISS stage 3, 19% IgA myeloma and 9% renal failure. Eight of 36 evaluable patients (22%) had high-risk cytogenetics. Patients had received a median of one prior line of therapy (range 1-4). All patients had received prior treatment with new drugs, such as thalidomide (57%), lenalidomide (54.5%), bortezomib (46.5%) or both (20%). Twenty-four patients (32%) were refractory to IMIDs. Best response rate was 75%, including 14 CRs (20%), 22 VGPRs (24%) and 27 PRs (31%). Five patients (6.5%) died early. Only prior treatment with bortezomib significantly reduced the response rate ≥ PR (48.5% vs 80%; P = 0.004). At a median follow-up of 27 months (range 18-38), 45 patients had progressed and 43 had died. Median TTP and PFS were 17 and 12.5 months, respectively while median OS was 24 months (40% at 3 years). After longer follow-up, prior therapy with bortezomib plus lenalidomide was confirmed as the only factor that significantly reduced TTP (9 vs 19 months; HR = 2.7; 95% CI = 1.3-5.8; P = 0.009), PFS (9 vs 15 months; HR = 2.1; 95% CI = 1.2-3.8; P = 0.020) and OS (17 vs 32 months; HR = 2.1; 95% CI = 1.2-3.9; P = 0.043). Grade 3-4 adverse events occurred in 55% of patients leading to therapy reduction in 24% and to protocol discontinuation in 11% of patients. The most frequent severe adverse events were thrombocytopenia (28%), neutropenia (20%), infections (12%), peripheral neuropathy (9%), gastrointestinal (5%) and cardiovascular events (4%). Compared with younger, patients aged 〉 70 years had a significantly higher incidence of grade 3-4 side effects particularly thrombocytopenia and infections with, consequently, a higher rate of therapy reduction and discontinuation. Moreover, 4/5 early deaths occurred in patients aged more than 70 years. Conclusions: BVD combination is an effective and well tolerated regimen in relapsed-refractory MM. Data suggest that the optimal target of BVD maybe patients younger than 70 years who has not previously received both bortezomib and lenalidomide. Disclosures Offidani: Mundipharma, Janssen: Honoraria. Off Label Use: Bendamustine. Corvatta:Janssen: Honoraria. Ballanti:Janssen: Honoraria. Brunori:Janssen: Honoraria.

Abstract: INTRODUCTION: Elderly patients with newly diagnosed multiple myeloma (NDMM) are highly heterogeneous and their outcome is influenced by many factors: beside age, also comorbidities, general physical fitness, and cognitive function play a crucial role. The IMWG frailty score combines age, functional status, and comorbidities, and it identifies fit, intermediate-fit and frail patients, with different risk of toxicity, treatment discontinuation, and mortality (Palumbo A et al. Blood 2015). Until now, evidence-based tailored treatments according to patients' frailty are still lacking. Therefore, this phase III study investigated the efficacy and feasibility of dose/schedule-adjusted lenalidomide-dexamethasone therapy followed by lenalidomide maintenance (Rd-R) versus continuous lenalidomide-dexamethasone (Rd) in elderly, intermediate-fit NDMM patients. METHODS: Intermediate-fit NDMM patients, with a total frailty score (age, Charlson Index, ADL and IADL) of 1 (http://www.myelomafrailtyscorecalculator.net/), were enrolled and randomized to receive Rd-R or continuous Rd. To better approximate a real-world older population, patients usually excluded from clinical trials or with abnormal laboratory values could be included in the trial. Rd-R treatment consisted of nine 28-day cycles of lenalidomide 25 mg/day for 21 days and dexamethasone 20 mg on days 1,8,15,22, followed by lenalidomide maintenance 10 mg/day for 21 days, until disease progression. Continuous Rd consisted of lenalidomide 25 mg/day for 21 days and dexamethasone 20 mg on days 1,8,15,22, until disease progression. The dose and schedule of continuous Rd was the one adopted in patients 〉 75 years in the FIRST trial (Hulin C et al. JCO 2016). The primary endpoint was event-free survival (EFS), defined as progression or death for any cause or discontinuation of lenalidomide or occurrence of any hematological grade 4 or non-hematological grade 3-4 adverse events (AEs), including Secondary Primary Malignancies (SPMs), whichever came first. RESULTS: 199 patients (98 in Rd-R arm and 101 in continuous Rd arm) could be evaluated. Patients characteristics were well balanced between the 2 arms. Median age was 75 and 76 years (p=0.06); 47% in Rd-R vs 57% in continuous Rd were defined intermediate-fit for age (≥76 years), 53% vs 43% due to an impairment in Charlson Index, ADL or IADL (p=ns). In intention-to-treat analysis, after a median follow-up of 25 months, EFS was 9.3 vs 6.6 months (HR 0.72, 95% CI 0.52-0.99, p=0.04), in Rd-R versus continuous Rd, respectively (Figure 1). Best response rates were not significantly different between the 2 groups: ≥PR rates were 73% vs 63%, and ≥VGPR rates were 43% vs 35% in the Rd-R vs Rd continuous group, respectively (p=ns). No difference in progression-free survival (PFS) and overall survival (OS) was observed. Median PFS was 18.3 vs 15.5 months (HR 0.93, 95% CI 0.64-1.34, p=ns) (Figure 1), 18 month-OS was 85% versus 81% (HR 0.73, 95% CI 0.40-1.33, p=ns). Adverse events accounting for EFS (any hematologic grade 4, non-hematologic grade 3-4) were less frequent in the Rd-R group (30% vs 39%) than in the continuous Rd group (p=ns). The most frequent adverse events were neutropenia, infection and skin reactions (less than 10% in each arm). After 9 treatment cycles, these adverse events were less frequent in Rd-R vs continuous Rd group (3% vs 7%, p=ns). Lenalidomide dose reduction after 9 treatment cycles was required in 1% of Rd-R patients and 21% of continuous Rd patients (p =0.06). Dexamethasone dose reduction was required in 17% vs 29% of patients, respectively (p=0.06). CONCLUSION: This is the first prospective randomized phase III trial specifically designed for real-life intermediate-fit NDMM patients. A dose/schedule-adjusted Rd-R treatment was more feasible compared to full dose continuous Rd treatment in elderly intermediate-fit NDMM patients, with no negative impact but rather a comparable outcome. These results confirm the need for an appropriate definition of patient frailty, and pave the way to a frailty-adjusted treatment approach to better balance efficacy and safety in elderly NDMM patients. Figure 1. Figure 1. Disclosures Larocca: Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria; Amgen: Honoraria. De Paoli:Amgen: Other: Advisory Board; Janssen: Other: Advisory Board; Celgene: Other: Advisory Board; Gilead: Other: Advisory Board. Galli:Celgene: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Sigma-Tau: Honoraria. Montefusco:Janssen: Other: Advisory Board; Amgen: Other: Advisory Board; Celgene: Other: Advisory Board. Caravita di Toritto:Johnson & Johnson: Other: Advisory Board, Travel and Accomodation EHA; Amgen: Other: Advisory Board; Bristol-Myers Squibb: Honoraria, Other: Travel and Accomodation EMN; Takeda: Other: Advisory Board; Celgene: Other: Advisory Board, Travel and Accomodation ASH, Research Funding. Giuliani:Celgene Italy: Other: Avisory Board, Research Funding; Takeda Pharmaceutical Co: Research Funding; Janssen Pharmaceutica: Other: Avisory Board, Research Funding. Patriarca:Jazz: Other: Travel, accommodations, expenses; Janssen: Other: Advisory role; Celgene: Other: Advisory Role; Travel, accommodations, expenses; Medac: Other: Travel, accommodations, expenses; MSD Italy: Other: Advisory Role. Offidani:Takeda: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Bristol-Myers Squibb: Honoraria, Other: Advisory Board. Cavo:GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Palumbo:Takeda: Employment. Boccadoro:Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Mundipharma: Research Funding. Bringhen:Janssen: Honoraria, Other: Advisory Board; Celgene: Honoraria; Amgen: Honoraria, Other: Advisory Board; Takeda: Consultancy; Bristol-Myers Squibb: Honoraria.

Abstract: High‐dose chemotherapy followed by autologous stem cell transplantation (auto‐SCT) is the standard treatment for young patient ≤65 years with multiple myeloma (MM). The role of auto‐SCT in elderly patients older than 70 years remains controversial in the era of novel agents and especially since the recent introduction of monoclonal antibodies (AbMo). In this study, we evaluated 12 patients with MM over 70 years old undergoing auto‐SCT (elderly graft cohort) in seven centers of GIMEMA Working Group Lazio. We compared the baseline characteristics, treatment and outcome with 97 MM elderly patients who did not receive auto‐SCT (nontransplant patients) from the same registry who were ≥ 70 years old, but did not undergo auto‐SCT. The median progression free survival (PFS) for graft versus no‐graft cohort was 56.4 versus 26.1 months, respectively. There was a trend for better PFS among graft compared to nontransplant patient (p = .1). On the other hand, the median overall survival for transplant versus nontransplant cohort was 107.6 versus 49.5 months (p = .02). Despite the small number of patients aged ≥70 years and ≤74 years, it seems that auto‐SCT is well tolerated, safe and effective. Therefore, we propose that it should be considered an important treatment option in the era of new drugs in elderly fit patients with MM.

Abstract: Lenalidomide plus dexamethasone is effective in the treatment of multiple myeloma (MM) but is associated with an increased risk of venous thromboembolism (VTE). This prospective, open-label, randomized substudy of a phase 3 trial compared the efficacy and safety of thromboprophylaxis with low-dose aspirin (ASA) or low-molecular-weight heparin (LMWH) in patients with newly diagnosed MM, treated with lenalidomide and low-dose dexamethasone induction and melphalan-prednisone-lenalidomide consolidation. Overall, 342 patients who did not have clinical indications or contraindications to antiplatelet or anticoagulant therapy were randomly assigned to receive ASA 100 mg/d (n = 176) or LMWH enoxaparin 40 mg/d (n = 166). The incidence of VTE was 2.27% in the ASA group and 1.20% in the LMWH group. Compared with LMWH, the absolute difference in the proportion of VTE was 1.07% (95% confidence interval, −1.69-3.83; P = .452) in the ASA group. Pulmonary embolism was observed in 1.70% of patients in the ASA group and none in the LMWH group. No arterial thrombosis, acute cardiovascular events, or sudden deaths were reported. No major hemorrhagic complications were reported. In previously untreated patients with MM receiving lenalidomide with a low thromboembolic risk, ASA could be an effective and less-expensive alternative to LMWH thromboprophylaxis. This study was registered at www.clinicaltrials.gov as #NCT00551928.