ALBERT

Description: Abstract 4445 Despite remarkable responses with imatinib in chronic phase chronic myeloid leukemia (CML-CP), there remains a proportion of patients who are resistant or intolerant to imatinib treatment. Dasatinib is effective second-line treatment for this patient population. Importantly, without effective therapeutic intervention, these patients inevitably progress to advanced phases of disease, have a short survival and declined health outcomes. This emphasizes the importance of patient-reported outcome assessment in these patients. Comprehensive information about the results of dasatinib therapy both in terms of clinical and patient-reported outcomes will be helpful in evaluation of risks/benefits of treatment in this patient population. We aimed to study response rates as well as quality of life (QoL) parameters and symptom profile in imatinib-resistant or -intolerant CML-CP patients receiving dasatinib. 38 CML-CP patients resistant or -intolerant to imatinib were enrolled in the study (mean age - 50 years old, SD 14.5; range −22–79 years; male/female – 19/19). The median of disease duration was 5.7 years (1–13 years). The median duration of imatinib treatment - 39 months (5–101 months). 33 patients had resistance to imatinib treatment; 5 patients were intolerant to imatinib. Patients received dasatinib in the dose of 100 mg daily. Median follow-up was 12 months. For QoL assessment patients filled out the SF-36 and for symptom assessment – Comprehensive Symptom Profile in Chronic Myeloid Leukemia Patients (CSP Leuk-CML). The CSP Leuk-CML is developed to assess profile of 47 symptoms specific for patients with CML. To compare patient population with normative data the sample from population norm (PN) database adjusted to age and gender was used. For comparisons Mann-Whitney test was used. Symptom severity and percentages of patients with symptoms at moderate-to-severe (ratings3 5) levels was evaluated. High rates of hematologic (complete, 90%) and cytogenetic (major, 85%; complete, 35%) response were observed for the majority of patients at 6 months from the start of therapy. During observation period two patients died (at 2 and 6 months after therapy initiation), one patient discontinued treatment due to significant thrombocytopenia at 2 months, and one patient discontinued treatment due to disease progression at 6 months after therapy initiation. At base-line patients experienced impaired QoL as compared to population norms: the values for the majority of SF-36 scales were significantly lower than in control group (p

Description: There is limited published data about the efficacy and safety of the second-line therapy with dasatinib in patients in chronic phase chronic myeloid leukemia (CML-CP) in a “real world” patients setting outside clinical trials. In addition, comprehensive evaluation of benefits and risks of the treatment is worthwhile to better define treatment outcomes in this patients’ population. We aimed to study clinical and patient-reported outcomes as well as safety of dasatinib treatment in a “real world” setting within the context of its approved indication through the analysis of prospectively collected data in patients with imatinib resistance or intolerance receiving dasatinib as the second-line therapy. 75 CML-CP patients resistant or -intolerant to imatinib were enrolled in the prospective, multicenter, non-interventional study (mean age 51.3 years old, SD 15.4; range 22–83 years; male/female – 37/38). The median of disease duration was 5.0 years (0.75–17 years). 63 patients had resistance to imatinib; 12 patients were intolerant to imatinib; the median duration of imatinib treatment 40 months (3–121 months). All the patients received dasatinib as the second-line therapy (100 mg daily). Median follow-up was 12 months. For quality of life (QoL) and symptom assessment patients filled out the SF-36 and Comprehensive Symptom Profile in Chronic Myeloid Leukemia Patients (CSP Leuk-CML), respectively, at base-line, in 1, 3, 6 months after treatment start and every 6 months thereafter. Comparison of QoL and symptom scores was conducted using t-test. QoL scores were analyzed using t-test, adjusting for sociodemographic and disease status. Mean symptom severity and percentage of patients with moderate-to-severe (ratings ³ 5) symptoms was evaluated. After 12 months of treatment 83% patients achieved or maintained complete hematologic response and 35 % – complete cytogenetic response. The twenty four-month progression free survival rate was 93% (95% CI; 84–97%). Four cases of pleural effusion events were registered: they were easily managed in 3 cases; one patient died at 1 month after treatment start due to accompanied infection complication. No severe hematological adverse effects were observed except two cases of grade III-IV neutropenia. Two patients were resistant to dasatinib. Two patients died of disease progression at 6 months of follow-up. At 12 months of dasatinib treatment QoL parameters were stable for 5 out of 8 scales; vitality, social functioning and mental health significantly improved as compared with base-line (p〈 0.01). At 24 months of dasatinib treatment improvement of physical functioning, vitality, social functioning and mental health as compared with base-line was registered (p〈 0.01); no worsening was observed for other QoL scales. Before treatment 75% of patients experienced at least one moderate-to-severe symptom; more than 40% had more than 7 moderate-to-severe symptoms. The majority of patients (96%) experienced fatigue; half of them suffered from moderate-to-severe fatigue. While treatment the number of patients with moderate-to-severe symptoms decreased. After 12 months of therapy only 25% of patients experienced moderate-to-severe fatigue. Before treatment 36% of patients exhibited critical or severe QoL impairment. Remarkably, in the subgroup of patients (44%) with critical or severe QoL impairment at base-line dramatic QoL improvement was observed: QoL index increased 3.4 fold (p

Description: Information about the efficacy and safety of the second-line therapy with dasatinib in patients in chronic phase chronic myeloid leukemia (CML-CP) at long-term follow-up is limited. Evaluation of benefits and risks of the treatment in a “real-world” study both from physician’s and patient’s perspective is worthwhile to better define treatment outcomes in this patients’ population. We aimed to study clinical and patient-reported outcomes as well as safety of the second-line therapy by dasatinib in CML-CP patients with imatinib resistance or intolerance treatment at long-term follow-up. 75 CML-CP patients resistant or -intolerant to imatinib were enrolled in the prospective, multicenter, non-interventional study (mean age 51.3 years old, SD 15.4; range 22–83 years; male/female – 37/38). All the patients received dasatinib as the second-line therapy (100 mg daily). Clinical and patient-reported outcomes were evaluated at base-line, 12, 18 and 24 months after treatment start. Twenty six patients were analyzed through all study time-points. For quality of life (QoL) and symptom assessment all the patients filled out the SF-36 and Comprehensive Symptom Profile in Chronic Myeloid Leukemia Patients (CSP Leuk-CML), respectively. Overall and progression-free survival rates as well as cumulative probability of achieving a complete cytogenetic response (CCgR) were calculated using Kaplan-Meier methods. To compare frequencies of CCgR χ2 criterion was applied. Comparison of QoL and symptom scores was conducted using t-test. QoL scores were analyzed using t-test, adjusting for sociodemographic and disease status. At 24 months of dasatinib treatment 94% patients achieved or maintained complete hematologic response and 69% – CCgR. The twenty four-month progression free survival rate was 79% (95% CI; 63.3–88%), overall survival rate – 93% (95% CI; 84–97%). One patient was resistant to dasatinib after 16 months of treatment. During the second year of dasatinib therapy one сase of pleural effusion (grade 3) was registered (at 18 months of treatment); other severe adverse effects (grade 4) were as follows: one patient – neutropenia (at 18 months), one patient – arthralgia/myalgia (at 18 months), one patient – memory loss (at 24 months), one patient – headache and hyperglycemia at 18 months and palpitations, alopecia, hyperglycemia at 24 months of treatment. At 24 months of dasatinib treatment improvement of QoL as compared with base-line was registered: Integral QoL index was significantly higher than at base-line (p

Description: Background. Ibrutinib became available for patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL) in Russia in the end of 2015 based on the results of phase 2 study by M. Wang from MD Anderson Cancer Center (NEJM 2013, Blood 2015). However, pts in routine clinical practice tend to differ significantly from the patients selected for clinical trials, which may lead to poorer results in off study treated patients. Aim. To assess efficacy and toxicity of ibrutinib monotherapy in pts with R/R MCL in routine community clinical practice outside of clinical trials. Materials & Methods. We analyzed the charts of all pts with R/R MCL who started ibrutinib from April 2016 to July 2019 in 7 Moscow's hospitals. The following criteria were used to initiate ibrutinib monotherapy: the age 〉 18 years, confirmed MCL diagnosis with nuclear hyperexpression of cyclin D1 and/or presence of the t(11;14)(q13;q32); symptomatic relapse or failure to achieve at least PR with a prior regimen. Poor physical status, pancytopenia grade 3-4, infectious complications (except for life-threatening conditions), blastoid variant and the number of previous treatment lines were not regarded as contraindications to ibrutinib therapy. Patients with CNS involvement were excluded from this analysis. Ibrutinib was administered once a day at a dose of 560 mg until progression or intolerable toxicity. Response to therapy was assessed every 2-3 months utilizing CT scan, PET/CT and bone marrow examination were required to confirm CR. Results. 54 pts with R/R MCL received ibrutinib monotherapy between April 2016 and July 2019. 26 pts (48%) were refractory to a prior therapy. The median age was 68 years (range 40-81); 69% of pts were men; ECOG 〉 2 in 22% of pts. 15 pts (28%) underwent a repeated biopsy before starting ibrutinib. 23 pts (43%) had an aggressive variant of MCL: either blastoid morphology (13/54 at diagnosis and 5/54 after repeated biopsy) or classical morphology with Ki-67〉40% (4/54 at diagnosis and 1/54 after repeated biopsy). The median number of previous treatment lines was 2 (1-11). The response was evaluated in 53/54 pts. ORR was 81%, CR rate was 30% in the whole group. Pts with aggressive variants of MCL (group 1) had ORR of 65%, CR rate of 7%. In the group with classical morphology and Ki-67≤40% (group 2) ORR and CR rates were 93% and 47%. 2 pts with a response to therapy stopped ibrutinib early on their own accord, without signs of toxicity above gr.1. The median EFS for all pts was 394 days (95% CI: 261-526). In group 1 the median EFS was 173 days (95% CI: 112-234), in the group 2 the median EFS was 759 days (95% CI: 521-996, p

Description: Introduction. Primary immune thrombocytopenia is a rare disease1. The incidence of ITP is not well estimated in Russia and worldwide. In adults it varies from 1,6 to 3,9/100 000 person-years2-3. The gender and age-associated results are discussed and differ in several investigations4-6. Study objectives: evaluation of the incidence of primary immune thrombocytopenia in adults in one region of Russia Patients and methods. The data source is the Registry of the patients with primary ITP in Russia. 272 adult patients: 77 males (28%) and 195 females (72%), age from 16 to 89 years (median 44 years) with ITP (ICD-10 code D69.3), newly diagnosed cases during the period from 12 Jan 2014 to 24 May 2016. Results. 221 (81%) cases were newly diagnosed in 12 regions of Russia in which registration was performed most actively - more than 5 cases for the duration of the study. But only one region was selected for the first evaluation of epidemiological characteristics because of the number of reasons. There is one hematological central clinic in this region in which diagnosis of ITP can be verified and patients with ITP are treated and monitored most properly. The early started and fully performed registration process can be regarded as covered most part of region population in this target region. 86 cases (27 male, 59 female) were registered in the target region. The gender-age distribution was following: male: age

Description: Introduction Few treatments options are available for patients (pts) with relapsed/refractory multiple myeloma (RRMM) who have previously been treated with lenalidomide (LEN) and bortezomib (BORT), and their prognosis is poor. Pomalidomide (POM) is a distinct IMiD® immunomodulatory agent with a mechanism of action consisting of direct anti-myeloma, stromal-support inhibitory, and immunomodulatory effects. In randomized phase 2 and 3 trials (MM-002 and MM-003), POM plus low-dose dexamethasone (POM+LoDEX) demonstrated marked efficacy in RRMM pts who had received multiple prior therapies, including LEN and BORT. This side-by-side analysis presents the most recent survival and safety data from these trials. Methods The MM-002 and MM-003 trials enrolled pts with ≥ 2 prior therapies, including LEN and BORT. In MM-002, pts received POM (4 mg/day on days 1–21 of each 28-day cycle) alone or in combination with LoDEX (40 mg/week). In MM-003, pts were randomized 2:1 to receive POM+LoDEX or high-dose DEX alone (HiDEX) (40 mg/days 1–4, 9–12, 17–20 in a 28-day cycle); HiDEX was chosen as the comparator to isolate the effects of POM, as at the time of trial design it was the standard salvage therapy for heavily pretreated pts. Thromboprophylaxis was required for all pts treated with POM and pts at high risk of developing venous thromboembolism. Data cutoff was February 1, 2013 for MM-002 and March 1, 2013 for MM-003. The primary endpoint in both trials was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rates, duration of response, and safety. Results In each study, pts had received a median of 5 prior therapies (range 1-17), and all pts had received prior LEN and BORT. In MM-002, 113 pts were treated with POM+LoDEX and 108 were treated with POM alone (60% of POM alone pts subsequently received DEX). A total of 79% of pts were LEN refractory; 62% were refractory to both LEN and BORT; and 35% had received LEN as their last prior therapy. With a median follow-up of 14.2 months (mos), median PFS was 4.2 mos, OS was 16.5 mos, and overall response rate (ORR, defined as at least a partial response) was 33% with POM+LoDEX (Table 1). In MM-003, 302 pts were treated with POM+LoDEX and 153 pts were treated with HiDEX (50% of HiDEX pts subsequently received POM). A total of 94% of pts were LEN refractory; 74% were both LEN and BORT refractory; and 29% had received LEN as their last prior therapy. Survival outcomes were similar in MM-003; with a median follow-up of 10 mos, median PFS was 4.0 mos, OS was 12.7 mos, and ORR was 31% with POM+LoDEX. In both trials, LEN as last prior therapy did not impact response, PFS, or OS vs the overall population. Commonly observed adverse events (AEs) are presented in Table 2 for pts treated with POM+LoDEX. Grade 3 and 4 neutropenia was 28% and 13% in MM-002, and 26% and 22% in MM-003 for the POM+LoDEX arms, respectively. AEs were generally manageable for POM+LoDEX in MM-002 and MM-003 with dose interruptions (67% for both) and reductions (29% and 26%, respectively), and standard supportive care, including growth factor support (46% and 43%), red blood cell transfusions (45% and 49%), platelet transfusions (14% and 20%), and anti-infective agents (89% in both trials). Rates of POM discontinuation due to treatment-related AEs were low (2–4% with POM+LoDEX). In MM-002 and MM-003, 49% and 51% of pts in the POM+LoDEX arms experienced neutropenia of any grade. With appropriate AE management, 9% and 23% had dose interruptions, 4% and 8% had dose reductions, and 1 pt in both MM-002 and MM-003 discontinued due to neutropenia. Febrile neutropenia developed in 3% and 10% of pts; 1% and 4% had dose interruptions, 0% and 2% had dose reductions, and no pts discontinued due to febrile neutropenia in the MM-002 and MM-003 studies, respectively. The majority of infections occurred in the absence of neutropenia of any grade (54% in MM-002 and 66% in MM-003). The rate of POM discontinuation due to infection was low (1% in MM-002 and 2% in MM-003). Conclusion In both the MM-002 and MM-003 trials, POM+LoDEX consistently extended PFS in advanced RRMM pts. PFS, OS, and ORR were not negatively impacted in patients who were refractory to LEN or BORT, even as last prior therapy. Both trials demonstrated that with dose modifications and supportive care POM was well tolerated, leading to few discontinuations. POM+LoDEX should be considered a standard of care for pts with advanced RRMM who have exhausted LEN and BORT. Disclosures: Siegel: Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Onyx: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Millennium: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Richardson:Millennium: Membership on an entity’s Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity’s Board of Directors or advisory committees; Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees. Dimopoulos:Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Song:Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vij:Onyx: Consultancy, Research Funding; Millenium: Speakers Bureau; Celgene Corporation: Consultancy, Research Funding, Speakers Bureau. Bahlis:Celgene Corporation: Consultancy, Honoraria, Research Funding. Baz:Millenium: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Celgene Corporation: Research Funding. Hofmeister:Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Weisel:Celgene Corporation: Consultancy, Honoraria, Research Funding. Jagannath:Millennium: Honoraria; Celgene Corporation: Honoraria. Lonial:Millennium: Consultancy; Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Sanofi: Consultancy; Onyx: Consultancy; Celgene Corporation: Consultancy. Delforge:Celgene Corporation: Honoraria. Talpaz:Ariad, Sanofi, Novartis: Membership on an entity’s Board of Directors or advisory committees; Ariad, Novartis, BMS, Pfizer: Speakers Bureau; Ariad, BMS, Sanofi, INCYTE: Research Funding. Moreau:Celgene Corporation: Honoraria, Speakers Bureau. San Miguel:Jansen, Celgene Corporation, Onyx, Novartis, Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Karlin:Janssen: Honoraria; Celgene Corporation: Consultancy, Expert board committee Other, Honoraria. Goldschmidt:Celgene Corporation, Janssen, Novartis: Consultancy, Honoraria, Research Funding. Oriol:Celgene Corporation: Consultancy. Alegre:Janssen: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Cavo:Millennium: 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; Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene Corporation: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Martinez-Lopez:Celgene Corporation: Honoraria, Research Funding. Lacy:Celgene Corporation: Research Funding. Chen:Celgene Corporation: Employment, Equity Ownership. Casey:Celgene Corporation: Employment, Equity Ownership. Sternas:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Jacques:Celgene Corporation: Employment, Equity Ownership. Anderson:Onyx: Consultancy, Equity Ownership; Gilead: Consultancy, Equity Ownership; sanofi aventis: Consultancy, Equity Ownership; Oncopep: Consultancy, Equity Ownership; Acetylon: Consultancy, Equity Ownership; Celgene Corporation: Consultancy, Equity Ownership.