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The characteristics of patients with RRMM in the real-world setting often differ from those enrolled in clinical trials, challenging therapeutic decisions in day-to-day practice. We retrospectively analyzed the sociodemographic and clinical characteristics of RRMM patients treated in routine clinical practice and their influence on the prescribing patterns in this setting. Treatment patterns among 276 RRMM patients from multiple hospitals were highly heterogeneous. The prescribed regimen was primarily influenced by the number of previous lines and the presence of osteopenia and extramedullary plasmacytomas. Our results rise awareness on the heterogeneity of the therapeutic landscape of RRMM in the real-world and highlight the complexity of therapeutic decision making in this population. Introduction: Treatment of relapsed and/or refractory multiple myeloma (RRMM) should be established based on multiple factors, including previous treatment and the sociodemographic/clinical characteristics of the patients. However, patients enrolled in randomized-controlled trials often do not mirror the scenario encountered in real-world practice, thus challenging therapeutic decisions in day-to-day practice. Patients and methods: This observational, cross-sectional, multicenter study aimed to investigate the sociodemographic and clinical characteristics of patients with RRMM treated in routine practice in Spain and their influence on treatment regimens. Results: The study included 276 RRMM patients (median age 69 years; no gender predominance). Seventy-four percent of patients had CRAB features at the time of study inclusion, 65.9% bone lesions, 28.7% high-risk cytogenetics, and 27.0% were at ISS stage III; 65.1% were retired and lived in urban areas (75.7%) with their relatives (85.8%); 28.7% had some dependence degree. Patients had experienced their last relapse in a median of 1.61 months before enrollment and had received a median of 2 treatment lines (range 1-10). Second-and third-line therapies were mostly based on immunomodulatory drugs, followed by proteasome inhibitors (PIs), whereas monoclonal antibodies prevailed in later treatment lines. The presence of extramedullary plasmacytomas, the absence of osteopenia, and being in the second or third treatment line (vs. later lines) significantly increased the odds of receiving PIs. Conclusions: RRMM treatment in the real-world setting is highly heterogeneous and is pr imar ily influenced by the number of previous lines. The consideration of patients' clinical and sociodemographic characteristics may support clinicians in making therapeutic decisions.

Introduction Treatment of relapsed/refractory multiple myeloma (RRMM) is highly challenging, especially for patients with disease refractory to initial therapy, and in particular for disease developing refractoriness to lenalidomide. Indeed, with currently approved treatments, median progression-free survival (PFS) in the lenalidomide-refractory setting is less than 10 months, reflecting the difficulty in treating this patient population. Pomalidomide is a second-generation immunomodulatory drug that has shown activity in lenalidomide-refractory disease in the setting of different combinations. Patients and Methods A real-world study was conducted by the Spanish Myeloma group in a cohort of patients with RRMM treated with pomalidomide, cyclophosphamide, and dexamethasone (PomCiDex). One hundred patients were treated with a median of 3 prior lines of therapy. Results Overall response rate was 39%, with a clinical benefit rate of 93%. Median PFS was 7.6 months; median overall survival (OS) was 12.6 months. Median PFS and OS survival were consistent across the different subgroups analyzed. Prolonged PFS and OS were found in patients with responsive disease. Conclusion Our results compared favorably with those obtained with different pomalidomide-based combinations in a similar patient population. PomCiDex remains a manageable, cost-effective, and all-oral triplet combination for RRMM patients.

© The Author(s) 2021., Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.

Introduction: The BCL-2 inhibitor venetoclax (Ven) has been approved on monotherapy or combined with rituximab in relapsed/refractory CLL patients (pts) and combined with obinutuzumab in previously untreated CLL pts. However, evidence from clinical trials can be difficult to generalize to real-world patient populations. The VENARES study assesses the real-world use of Ven following approval to inform of subpopulations underrepresented in clinical trials. Methods: This is Spanish non-interventional retrospective, multicenter post-marketing observational study. The main objective was to evaluate the effectiveness of Ven in adult CLL pts by the overall response rate (ORR) at 9 months (mo) after the first Ven dose administration. Secondary objective was to evaluate the effectiveness for the Ven monotherapy and the Ven combined with rituximab subpopulations. Consecutive adult pts with diagnosis of CLL who have initiated Ven at least 9 mo before the inclusion in the study were included. Data of pts are retrospectively reviewed until the date of last follow-up or death. Results: 125 pts diagnosed with CLL and who met the eligibility criteria were analyzed. The median age was 72 years (67 - 77) with 76.8% being older than 65 years. Most patients were male (68.8%), had a concurrent disease (65.6%). ECOG PS was recorded in 76 pts: 40 pts (32%) had PS 0, 30 pts (24%) PS 1 and 6 pts (4.8%) PS 2. Pts had received a median of 4 prior lines of therapy (range 1-13 lines). At baseline, among the 92 pts with known Binet stage, 31 (33.7%) had stage C and 38 (41.3%) had stage B; bulky nodes ≥ 5 cm were present in 20 of 87 pts; 49 pts (39.2%) had an absolute lymphocyte count ≥ 25 x 10 9/L and 33 of 54 pts (61%) baseline beta-2 microglobulin value above of 3500 ng/mL. In total, 29 of 90 patients (32%) assessed had Cr 17p deletion, 28 of 86 patients (32%) tested had TP53 mutations, and 46 of 56 patients (82%) who were tested had unmutated immunoglobulin heavy-chain variable (IGHV) status. Ven was administered as monotherapy in 71 pts (57.6%), combined with rituximab in 36 pts (28.8%), combined with obinutuzumab in 5 pts (4%) and combined with other drugs in 13 pts (10.4%). 83 of 125 patients included were evaluable for the primary objective of the study: the ORR at 9 mo was 84.3% (70 patients): CR/CRi in 44 (53%) pts, PR/nPR in 26 pts (31.3%), SD in 9 pts (10.8%) and PD in 4 pts (4.8%). By treatment, in the evaluable patients, ORR at 9 months were 79.2% (38 of 48 patients) in the Ven monotherapy group, with 45% of CR/CRi, and 92.3% (24 of 26 patients) in the Ven combined with rituximab, with 61% CR/Cri. The median duration of PFS was not reached at the time of the analysis (1-June-2021). Kaplan-Meier estimates of the probability of PFS at 24 mo was 75.4% (95% CI, 58.2 - 86.3). Disease progression occurred in 21 pts. Assessment of minimal residual disease (MRD) was available for 32 patients (25.6%) on the basis of peripheral-blood samples, bone marrow or both. Best undetectable MRD was reached in fourteen patients (43.8%). uMRD was more common in pts treated with Ven combined with R (83.3%, 5 of 6 pts) than in pts treated with Ven monotherapy (33.3%, 7 of 21 pts). Adverse events (AEs) were reported during Ven therapy in all 125 patients, 93 of these pts reported AEs related to Ven. Related to Ven, 67 patients (53.6%) experienced at least one AE: 52 pts (41.6%) had neutropenia being grade 3 and 4 in 22 (42.3%) and 9 (17.3%) pts, respectively. 9 pts (7.2%) had febrile neutropenia. Thrombocytopenia and anemia were less common occurring in 5.6% and 2.4%, respectively. Tumor lysis syndrome (TLS) occurred in 4 of 125 pts during ramp-up (3 laboratory and 1 clinical), 2 of them were related to Ven both lab TLS. None of the pts discontinued therapy due to TLS. Richter transformation was observed in 6 pts (4.8%). Other common AEs was diarrhea (10.4%), but most cases were mild. Conclusions: Our first real-world data show that Ven monotherapy or combined with rituximab is effective in highly pre-treated CLL patients, ORR at 9 mo was 84.3% in all population and PFS estimate at 24 mo was 75.4% with similar outcomes to those in the pivotal clinical trials. The safety profile of Ven was consistent with prior experience of Ven in monotherapy or combined with rituximab and no new safety signals were detected. Disclosures Baltasar: Janssen, Abbvie: Consultancy. Terol: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; BMS: Consultancy; Roche: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Hospital Clinico Valencia: Current Employment. Moreno: Janssen, Abbvie: Research Funding; Abbvie, Janssen, AstraZeneca: Speakers Bureau; Abbvie, Janssen, AstraZeneca, Beigene: Membership on an entity's Board of Directors or advisory committees. Osorio: Janssen, Abbvie, Roche: Consultancy. De la Cruz: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: 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; Kyowa Kirkin: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. de la Serna: AbbVie, AstraZeneca, Roche: Speakers Bureau; ABBVIE, ASTRAZENECA,ROCHE: Research Funding; AbbVie, AstraZeneca, Beigene, Gilead, GSK, Janssen, Jazzpharma, Novartis, Roche: Consultancy. Arguiñano: Takeda, Sanofi, Janssen, BMS-Celgene, Abbvie: Speakers Bureau; Takeda, Sanofi, Janssen, BMS-Celgene, Abbvie: Consultancy. Loscertales: Janssen, Abbvie, Roche, Gilead: Speakers Bureau; Janssen, Abbvie, Astra-Zeneca, Beigene, Roche, Gilead: Consultancy. García: Janssen, Roche, Gilead, Celgene: Consultancy; Janssen, AbbVie: Research Funding; Janssen, Roche, Gilead, AbbVie, Celgene: Other: medical meetings funding. Pérez Persona: BMS/Celgene: Consultancy, Other: Support for attending meetings and/or travel, Speakers Bureau; Amgen: Consultancy, Other: Support for attending meetings and/or travel, Speakers Bureau; Takeda: Speakers Bureau; AbbVie: Other: Support for attending meetings and/or travel, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; GSK: Consultancy; Incyte: Consultancy. Pérez-Encinas: Janssen: Consultancy. Caballero: Celgene, Janssen, Novartis, Abbvie: Speakers Bureau; Celgene, Janssen, Amgen: Consultancy. Ruiz-Zorrilla: Abbvie: Current Employment. Moreno: abbvie: Current Employment. Ferrà: Janssen, Roche, Gilead, Takeda, Abbvie: Consultancy; Janssen, Roche, Gilead, AbbVie: Other: medical meetings funding.

Introduction. Ibrutinib is a first-in-class, oral, once-a-day Bruton's tyrosine kinase inhibitor that achieves high overall response rates and durable remissions in patients with chronic lymphocytic leukemia (CLL) including those with high-risk features (unmutated IGHV, TP53 abnormalities, 11q deletion). Survival with continuous single-agent ibrutinib in previously-untreated CLL patients is comparable to an age-matched general population (Figure 1). IBRORS is an observational, retrospective, multicentre study to describe the characteristics and clinical outcomes of patients with CLL treated with single-agent ibrutinib in routine clinical practice in Spain. This present analysis reviews the subset of patients in IBRORS who received ibrutinib as the first-line of treatment. This series includes a significant number of patients with high risk cytogenetic/molecular alterations (del17p/TP53 M), which corresponds with the approved indication for first-line CLL patients in Spain at the time. Methods. Adult patients diagnosed with CLL treated with single-agent ibrutinib in first-line, or at first or second relapse since its commercialization in Spain (between January 2016 to January 2019) were included in the IBRORS study. Clinical characteristics of patients, efficacy and tolerability of ibrutinib as first-line treatment were analyzed here. A Kaplan-Meier analysis was performed for overall survival (OS) and progression-free survival (PFS). Results. 84 patients, from a total of 269 included in IBRORS, received single-agent ibrutinib as first-line treatment. The median age was 71.3 years (range 63-77) at the time of ibrutinib initiation. 56.3% of patients presented with an intermediate/high-risk Rai-Binet stage, and the majority of patients (98.6%) had an ECOG PS of 0-1. 91.7% of patients had at least 1 high risk molecular cytogenetic factor (unmutated IGHV, TP53 abnormalities, 11q deletion or complex karyotype) described in table 1. Baseline comorbidities of patients are described in table 2. Concomitant medication included anticoagulants (9.5% patients; vitamin K antagonist [n=4], Apixaban [n=1] and LMWH [n=3] patients), antiplatelet agents (11.9% patients), and antihypertensives (50% patients). The overall response rate (ORR) was 79.5%; 14/84 (16.6%) achieved a complete response (CR), 14/84 (16.6%) achieved CR unconfirmed, 27/84 (32.14%) achieved a partial response (PR) and 12/84 (14.2%) a PR + lymphocytosis. The median PFS and OS were not reached, and the estimated PFS at 24 months was 84.5% (73.4-95.6%). OS and PFS curves are represented in figure 2. The PFS of each patient subgroup with high-risk cytogenetic characteristics was similar to that of all patients in the first-line cohort: del17p/TP53 mutation (HR = 0.963 [95% CI 0.188-4.928]; p = 0.964), del11q (HR = 0.042 [95% CI 0.000-682.736]; p=0.521), unmutated IGHV (HR = 0.391 [95% CI 0.110-1.394]; p = 0.148). The median duration of exposure to ibrutinib was 17.3 (11.9-25.6) months. Dose reduction of ibrutinib occurred in 17/84 (20.2%) patients, 8/84 (9.52%) due to toxicity (4 hematologic toxicity and 4 non-hematologic toxicity). 27/84 (32.1%) patients had temporary interruption of treatment. 15/84 (17.8%) patients permanently discontinued ibrutinib including 6 (7.14%) patients due to progression, 4 (4.76%) due to toxicity and 5 for other reasons. Safety: 49/84 (58.3%) patients developed at least one adverse event (AE), while 12/84 (14.2%) patients developed at least one serious adverse event (SAE). Twelve (14.3%) patients reported at least one haematological toxicity while 53 patients (63.1%) recorded at least one non-haematological toxicity. Only 1 patient experienced grade 3 atrial fibrillation, which did not lead to discontinuation. The most common AEs are described in table 3. Conclusion. This population of previously-untreated CLL patients, enriched for high-risk genomic features, reflects the initial approval of ibrutinib for the treatment of first-line patients with del17p in Spain. Single-agent Ibrutinib as the first-line treatment in this real world population was effective regardless of risk factors and well tolerated, with a low rate of discontinuation due to toxicity. Findings are consistent with those reported in clinical trials. Disclosures Loscertales: AbbVie: 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; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria. Arguiñano:AbbVie: Honoraria; Janssen: Honoraria; BMS-Celgene: Honoraria; Novartis: Honoraria. Hernandez-Rivas:Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees. Pérez Persona:Amgen: Consultancy; Celgene: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Jannsen: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Takeda: Consultancy. Loriente:Janssen Cilag: Current Employment. Villanueva:Janssen Cilag: Current Employment.

Achieving and maintaining a high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients aged ≤65 years with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with IV busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the rates of a very good partial response or better were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response rate of 33.4% after induction in the intent-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 × 10(−6) sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%). The most common grade ≥3 treatment-emergent adverse events during induction were neutropenia (12.9%) and infection (9.2%). Grade ≥2 peripheral neuropathy (grouped term) during induction was 17.0%, with a low frequency of grade 3 (3.7%) and grade 4 (0.2%) events. VRD is an effective and well-tolerated regimen for induction in NDMM with deepening response throughout induction and over the course of treatment. This trial was registered at www.clinicaltrials.gov as #NCT01916252 and EudraCT as #2012-005683-10.