Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5497-5497

Abstract: Background Multiple myeloma (MM) is a frequent hematologic malignancy. The current gold standard frontline strategy includes a proteasome inhibitor (PI)-based induction, followed by autologous stem cell transplant (ASCT). Access to novel drugs in Latin America (LA) is limited. ASCT is available in most countries, but real access to it is highly heterogeneous. Data regarding patients´ outcomes in candidates to ASCT in the region is scarce. The aim of this study was to describe clinical characteristics and outcomes of MM transplant eligible patients in LA countries. Material and Methods Retrospective international multicenter cohort study. Consecutive MM transplant- eligible patients diagnosed between 2010 and 2018 from participating centers in Chile, Argentina, Ecuador, Mexico, Colombia, and Uruguay were included. Data were collected from clinical records in a standardized report form. We analyzed clinical characteristics at diagnosis and frontline therapy outcomes, including ASCT. Transplant-eligible patients were defined as fit patients younger than 66 years old. Active MM and response to treatment were defined according to current IMWG criteria. Inclusion criteria: 1.- Patients with newly diagnosed active MM between 2010 and 2018. 2.- Older than 18 years, and younger than 66 years. 3- Candidates for ASCT according to the evaluation of the attending physician Exclusion criteria: 1- Lack of minimum data in the clinical history 2- Plasma cell leukemia, AL amyloidosis or solitary plasmacytoma. 3- HIV infection 4-No consent and/or Ethics Committee approvals. Statistical analysis A descriptive statistic has been done. Comparisons of characteristics between groups was made usingT-student, Chi2 or ANOVA, as appropriate. Survival analysis was performed using Kaplan-Meier curves. Comparisons of survival between groups were made by the logarithmic recording method and the calculations of the risk relationships by Cox regression. Statistical analysis was performed by using STATA 13. Results We included 1293 patients in the study, 363 from Chile, 395 from Argentina, 209 from Colombia, 45 from Ecuador, 151 from Mexico, and 130 from Uruguay. The main characteristics at diagnosis and therapeutic strategies are shown in Table 1. Optimal response (sCR, CR and VGPR) was achieved in 38% of the patients in the cyclophosphamide, bortezomib, and dexamethasone (CyBorD) group, in 46% in the bortezomib, thalidomide, and dexamethasone (VTD) group, and in 36% in the cyclophosphamide, thalidomide, and dexamethasone (CTD) group, the 3 main induction regimens used. Only 53% of patients finally received ASCT. Significant differences were found between both groups, private and public institutions, regarding burden of symptoms, ISS staging, access to PI based induction, ASCT completion and adequate maintenance, with patients from the latter being more symptomatic, and receiving suboptimal therapy. FISH analysis was performed in less than 50% of patients, both in the public and private setting. With a median follow up of 34 months (range 1-113), median overall survival (OS) was 86 months. The 5-year progression free survival (PFS) was 38% and 5- year overall survival (OS) was 64%. When comparing public vs private settings, 5 year OS was 45% vs 80%, with a median OS of 56 months vs not reached, respectively (P 〈 0,0001). In the multivariable analysis renal failure (p=0.03), achieving less than VGPR response (p 〈 0.0001), not undergoing ASCT (p=0.001), and not receiving maintenance (p=0.005) were independent factors associated with worse outcome. Conclusion This is the largest report on transplant eligible patients with MM in LA. Great inequities are shown between public and private health systems. Survival in transplant-eligible patients is lower than that described in other regions. Only one third of patients had FISH performed. This means that very few patients are treated with a risk-based induction in LA. Patients in the public setting are diagnosed with a more symptomatic disease, probably due to a late diagnosis. OS is significantly worse in the public setting. This might be explained by the significant differences in access to PI-based induction, ASCT and maintenance between private and public institutions, with patients from the latter receiving suboptimal frontline therapy and maintenance. Reasons for 47% of potential candidates not being transplanted merit further analysis. Table 1 Disclosures Peña: Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfeizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Abello:Takeda: Other: Participation in advisory board meeting. Gomez-Almaguer:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-127555

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5508-5508

Abstract: Background Multiple myeloma (MM) is a heterogeneous disease that is most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the young population are scarce and it is recognized that it remains incurable even in this group of patients. We present here the outcomes of patients under 40 years old cohort in Latin-American countries. On behalf of GELAMM (Grupo de Estudio Latino-Americano de Mieloma Múltiple). Methods Retrospective international multicenter cohort study. We analyzed MM patients under 40 years old who received treatment in 6 Latin-American countries, between 2010 and 2018. Demographics and disease features were analyzed using descriptive statics. We examined treatment characteristics and response rates. The overall survival (OS) of the entire cohort was analyzed using Kaplan-Meier curves. Results Eighty-six patients of 6 countries were analyzed (Table1). The mean age was 35.4 years old, and 60% were male. The most frequent monoclonal component type was IgG followed by light chain MM. Risk determined by ISS was distributed in almost equal percentages. The most frequent cytogenetic alteration was the t (4;14) that was found in four patients out of 25 evaluated. The missing data were greater than 70%. Skeleton-related events were the most frequent clinical feature, followed by anemia and renal failure. Plasmacytomas and fractures were present in more than 20 percent of cases. With regard to treatment, VCD / CyBorD was the most used regimen, followed by VTD. The overall response rate (ORR) was 63%. Fifty-three patients received high dose therapy and autologous stem cell transplantation (62%). Only 8% received post-transplant consolidation, and 45% received maintenance therapy. The median OS of the entire cohort was 45 months, and a plateau in the survival curve was not observed, suggesting that patients continue relapsing over the time. Conclusion In this Latin American multicenter study, we found that the young population with MM has similar presentation characteristics to those of elderly patients. A significant amount of information is lost regarding the risk characterization, especially in regard with cytogenetics. With respect to treatment, less than half of the patients achieve very good partial response or better. It is striking that more than a third of this young patients did not access to high doses of chemotherapy and bone marrow transplantation. Maintenance therapy is offered to less than half patients. The median OS is lower than in other series of patients younger than 40 years, even than in the elderly cohorts. Prospective multicentric studies are required to elucidate the behavior of the disease in this group of patients. Disclosures Peña: Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights. Rojas:Novartis: Membership on an entity's Board of Directors or advisory committees; Pfeizer: 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. Abello:Takeda: Other: Participation in advisory board meeting. Gomez-Almaguer:Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-130987

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

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In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2786-2786

Abstract: BACKGROUND: Despite the excellent prognostic of chronic myeloid leukemia (CML) patients since the introduction of tyrosine kinase inhibitors (TKIs), approximately 50% of patients that are treated with TKIs will discontinue first line treatment due to lack of efficacy or intolerance. Once patients need a second line treatment, a considerable proportion of patients will need third or even fourth line therapy during further evolution. At this moment, there is a lack of data about real benefit of this group of patients. We have recently published our experience of 30 CML patients treated with bosutinib in 4th line. We present an update of the study where we have increased the number of patients, and the follow-up. The aim of this study is to present safety and efficacy data CML chronic phase patients treated with bosutinib in 4th line. METHODS: We have collected data from 59 CML patients treated with bosutinib in 4th line after resistance or intolerance to IM, NI and DA. 51 patients have been treated under the Spanish compassionate use program (36 centers) and 10 patients were treated in a single institution from United Kingdom. Median age of patients at diagnosis was 53 years. The percentage of low, intermediate and high risk Sokal groups were 47%, 37% and 16%. Median time TKIs exposure before bosutinib was 9 years. The most common indication (30/59) was intolerant to DA and NI. Patients' dispositions and main line characteristics are shown in table 1. RESULTS: Median follow-up was 14.3 months. All patients started bosutinib at 500mg/d, median dose of was 450mg/d. Overall probabilities to either achieve or maintain previous response were 96% (57/59), 62% (37/59), 40% (24/59) and 17% (10/59) for complete hematological response (CHR), complete cytogenetic response (CCyR), major molecular response (MMR) and MR4.5 respectively. However, probabilities to obtain responses (in patients without response evaluated at baseline) were 27% (7/26), 26% (12/45) and 12% (7/55) for CCyR, MMR and MR4.5. As expected, probabilities to obtain CCyR were lower for patients resistant to DA and NI patients than for patients intolerant to DA and NI (8% VS 44%). Event free survival (EFS) and progression free survival (PFS) probabilities were 50% and 83% by 27 month. Treatment was discontinued in 20/58 (34%), most frequent reasons being adverse events 9/59(15%), lack of efficacy 5/59 (8.5%), disease progression 2/59 (3.4%) and death 1/59 (1.7%). Two patients discontinued due to stem cell transplantation. The adverse events that led to treatment discontinuation were pleural effusion (3), diarrhea (2), rash, renal impairment, auricular fibrillation and liver enzyme elevation one patient each. Overall, bosutinib was well tolerated. Grade 3-4 hematological toxicities were 3%, 6% and 6% for anemia, thromboctytopenia and neutropenia. Most common non hematological side effects were diarrhea (39%, nauseas 13% and liver alterations 14% and pleural effusion 14%. CONCLUSIONS: Little is known about the therapeutic role of Bosutinib in 4th line. The series presented here is, to our knowledge, the largest being presented. Bosutinib seems to be an appropriate treatment option for patients resistant or intolerant to three prior TKIs. Table 1. IM+NI-I+DA-R (N=4) IM+NI-R+DA-R (N=18) IM+NI-I+DA-I (N=30) IM+NI-R+DA-I (N=7) Total (N=59) Sex, N (%) Male 2 (50) 11 (61.1) 16 (53.3) 2 (28.6) 31 (52.5) Median age of diagnosis, yr (range) 57.32 (50-64) 49.19 (23-73) 54.95 (21-89) 48.87 (26-68) 53.15 (21-89) Median age of Bosutinib initiation, yr (range) 69.13 (61-70) 62.27 (39-79) 64.85 (25-90) 64.79(35-74) 63.7 (25-9) Median follow up, months (range) 18.5(7.8-34.1) 8.4(1.22-36.1) 16.3(0.5-34.7) 23.4(3.3-28.9) 14.3(0.7-36.1) SOKAL Index at diagnosis, N (%) High 2(50.0) 4 (23.5) 1 (4.3) 1 (20) 8 (16.3) Intermediate 1 (25.0) 5 (29.4) 10(43.5) 2 (40) 18 (36.7) Low 1 (25.0) 8 (47.1) 12 (52.2) 2 (40) 23 (46.9) Median Time from first TKI to BOS, (yr, range) 10.3 (4.8-11.9) 9.3 (2.0-11.4) 8.8 (0.7-13.6) 8.2 (5.1-12.3) 8.8 (0.7-13.6) Median duration of prior therapy, months (range) Imatinib 38.8 (11.8-69.8) 32.6 (6.3-96.8) 26.2 (1.6-102.6) 23.1 (8.3-66.8) 28.8 (1.6-102.6) Dasatinib 21.5 (12.6-75) 21.8 (7.7-69) 31.4 (0.4-87.1) 23.7 (10.3-53.6) 23.44 (0.4-87.1) Nilotinib 19.1 (2.1-46.2) 16.7 (5-65.6) 8.9 (0.2-58.5) 30.9 (6.9-49.3) 14.3 (0.2-65.6) BOS: bosutinib, IM, imatinib; DA, dasatinib; NI, nilotinib, I: Intolerance, R: Resistant, Yr: year Disclosures García-Gutiérrez: Ariad: Consultancy; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Milojkovic:Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Ariad: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Boque:Novartis: Honoraria; BMS: Honoraria; Celgene: Honoraria. Casado:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Jiménez:Pfizer: Consultancy, Honoraria. Giraldo:Pfizer: Consultancy. Steegmann:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Ariad: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2786.2786

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 7189-7191

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-158104

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 3908-3910

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-169631

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 3925-3928

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-167453

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4788-4788

Abstract: INTRODUCTION: paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, non malignant disease of hematopoiesis characterized by intravascular hemolysis, a variable depth of bone marrow failure and a marked thrombophilia. Classic therapeutic resources are supportive care and allogeneic hematopoietic stem cell transplantation. Eculizumab arrival to our country -in 2009- revolutionized PNH treatment. We report here our experience with a cohort of 33 patients treated with eculizumab. AIMS: to evaluate indications of eculizumab, hematologic response, delays to initiate treatment, interruptions and its consequences, and mortality in our patients. PATIENTS and METHODS: data of 33 patients with PNH who begun treatment with eculizumab between '01/09 and '12/14 were collected with a specific questionnaire. Qualitative data were analyzed as proportions. Quantitative data were evaluated as median (Md), range (R) and percentiles 25% and 75%, or mean (Mn) and 95% confidence interval (95% CI). Quantitative responses to treatment were evaluated with a non parametric test for paired data (Wilcoxon signed Rank test). A probability value 〈 0.05 was used to define statistical significance. RESULTS: cohort characteristics: Md age at diagnosis: 32 years old. R: 18 a 73. Eighteen were females and 15 males. Interval simptoms-PNH diagnosis Md: 284 days, R: 1 a 4,518. Granulocyte PNH clon size Md: 91%, R: 18 a 99%. Symptoms prevalence: fatigue: 90.6%, dyspnea: 71.9%, abdominal pain 56.2%, dysphagia 25%, erectil dysfunction: 20% (of males). Complications frequency: thrombosis 27.3%, impaired renal function 21.2%, pulmonary hypertension 3.1%. Severity criteria of PNH leading to eculizumab prescription: disabling symptoms 90.6%, steroid dependence 70%, transfusional requirement 54.5%, thrombosis 24.2%, impaired renal function 21.2%, severe dyspnea/ pulmonary hypertension 21.2%. Delay of eculizumab treatment (from medical prescription to first infusion) in 28 patients: Md: 196 days, R: 37 to 592. Hematologic responses to eculizumab: Mn LDH decline: 2,081 U/L (95% CI: 1,204 to 2,958) p=0.0003. Mn elevation of hemoglobin 1,5 g/dL (95% CI: 0.82 to 2.18) p=0.0005. Platelet counts increase in thrombocytopenic patients ( 〈 150,000 platelets/µL) Mn: 20,720/µL (95% CI: 712 to 40,730) p=0.042. There were no significant changes in neutrophil counts. Eculizumab treatment interruptions were extremely frequent: 93.7% of patients suffered at least one or more treatment delay(s) ≥ 7 days. Only 2/33 patients did not have any treatment interruption. The mean cause of this treatment irregularities were delays in drug provision by the medical insurance (in 100% of affected patients). In only 10% of cases, lack of patient adherence was responsible for treatment interruptions. Even more, 25.8% of drug supplies were delayed for 7 days or more (99/384 provisions). Results of treatment interruptions were: transfusional requirement in 41.4% of cases, severe anemia in 34.5%, hospital admission in 27.6%, acute renal impairment in 16.7%, Budd-Chiari syndrome progression in one case, and probable cause of death in another one. Three patients died (9.1%). Causes were infection in 1, advanced colon cancer in 1, and multiorgan failure, probably related to visceral thrombosis, in the third case. CONCLUSIONS: this argentinian cohort shows that disabling symptoms, corticosteroids dependence and transfusional requirements are the most frequents causes to start eculizumab treatment in our patients. Eculizumab was effective to block hemolysis, to improve anemia and thrombocytopenia and to prevent new thrombotic events. However, eculizumab achievements were hindered in our experience by the delay to initiate treatment and the frequent interruptions it suffered, as it is usual in Latin America. These treatment delays/interruptions, uncommon in the medical literature, led to multiple and severe complications. Disclosures Brodsky: Alexion Pharmaceuticals: Consultancy, Speakers Bureau. Touliet:Alexion Pharmaceuticals: Speakers Bureau. Dinardo:Alexion Pharmaceuticals: Speakers Bureau. Blanca:Alexion Pharmaceuticals: Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.4788.4788

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 8963-8965

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-163869

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5523-5523

Abstract: Second-generation TKIs have demonstrated efficacy and an acceptable tolerability in patients (pts) with chronic myeloid leukemia (CML); however, new data from so called “off target” side effects have been published. For example, serious concerns have been raised about cardiovascular (CV) events with ponatinib, and, in lesser degree with nilotinib (NI), impeding or difficulting the treatment in patients with previous CV risk factors. Besides, patients with previous history of pleural effusion or pulmonary hypertension should avoid dasatinib (DA) if possible. Bosutinib could be a good candidate for situations which preclude the use of other TKI’s. We have previously presented efficacy data of 29 patients treated with bosutinib in forth line. The aim of this study is to report safety data of heavily CML patients treated with bosutinib in 4th line. We have studied 30 pts previously treated with imatinib (IM), dasatinib and nilotinib and 5 pts previously treated with IM-DA or NI since 2012 under the Spanish Compassionate Use Program. Patient’s baseline characteristics and previous treatments are shown in table 1. We have classified patients in 2 groups regarding to investigator-driven cause of discontinuation: intolerant (INT) or resistant (RES). At the data cutoff on June 16, 2014, the median follow up was 11.47 months (range, 2.03-45.97 months). Median duration of BOS treatment across all cohorts was 9.23 months (range, 0.63-23.40 months). We observed no significant differences in terms of Index prognostic factors (Sokal, Hasford or Eutos), sex, median duration of TKIs treatment or comorbidities. However, patients with resistance where significantly older observed: 56 years vs. 67 years (p 〈 0.05). Toxicity spectrum pre-BOS: Main reason for treatment discontinuation for each TKI was: treatment failure in the case of IM (14/35) and intolerance for both DA 16/34 and NI 13/31. Hematological (HEM) toxicities grade 3-4 with all TKIs were more common in RES pts, being dasatinib the one that showed the highest rate of grade 3-4 HEM toxicities. Non-HEM toxicities to all TKIs were significantly more frequent in INT than in RES pts (p 〈 0.05). Most common grade 3-4 non-HEM toxicities were rash for IM (3/35), pleural effusion for DA (7/34) and vascular events for NI (3/31 Peripheral arterial disease (PAOD), 3/31 Ischemic heart disease (IHD)). Toxicity spectrum with BOS treatment: treatment interruptions were more frequent in INT than in RES pts 52% vs 25%, as well as dose reductions 78% vs 66% respectively. Grade 3-4 HEM toxicities were more common in RES than INT pts (41.6% vs 4.3% respectively). Non-HEM toxicities were also more frequent in RES pts than INT: diarrhea (50% vs 43%), rash (16% vs 8%), ALT or AST increase (25% vs 13%) abdominal pain (16% vs 4%), grade 3-4 non HEM toxicities were more frequent in RES than INT pts (41% vs 17%) (Diarrhea 16.7% vs 4.3%, AST/ALT increase: 16.7% vs 0%). None (0/12) vs 4/23 (17%) pts discontinued treatment due to toxicity in the RES vs. INT group respectively. Cross intolerance was extremely rare, of the 7 pts who had rash with IM, only 1 suffered rash with BOS. None pts had pleural effusion with BOS out of 15 who previously suffered with DA neither vascular events out of the 10 pts that previously suffered with NI. EFS by 20 months was 75% vs 50% for INT and RES patients. We have shown how in previously heavily pretreated CML patients, most of them in 4th line bosutinib has an excellent safety profile with no patients interrupting treatment due to side effects in previously intolerant patients. Importantly, rates of cross intolerance (namely CV, pleural and skin ) have also been very low. We conclude that Bosutinib is an excellent alternative also in patients who are left without a suitable treatment option. Table IM+NI-I +DA-R IMA+NI-R +DA-R IM+NI-I +DA-I IM+NI-R +DA-I IM+NI/DA TOTAL Pts, N(%) 2 (5.7) 7 (20) 15 (43) 6 (17) 5 (14) 35 (100) Age of diagnosis, med yr 61.0 46.7 54.7 53.8 58.7 54.2 Age of BOS initiation, med yr 74.7 61.5 64.6 64.8 65.5 63.8 Sokal index at diagnosis, N (High/intermidiate/low) 1/0/1 1/2/4 0/5/7 1/2/2 0/2/2 3/11/16 Time from first TKI to BOS, med yr 11.7 10.0 9.9 7.4 10.7 10.0 Duration of IM treatment, med, mo 63.3 33.1 26.6 21.4 78.2 27.2 Duration of DA treatment, med, mo 48.7 16.0 41.9 19.2 18.7 23.6 Duration of NI treatment, med ,mo 29.1 14.2 9.0 21.0 24.2 11.6 I:iIntolerance, R: resistant, med: median, yr: year, mo: months Disclosures García-Gutiérrez: Novartis: Consultancy; BMS: Consultancy; Pfizer: Consultancy; Ariad: Consultancy. Steegmann:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Ariad: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.5523.5523

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

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In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 49-50

Abstract: Introduction: Asciminib is a new BCR-ABL1 inhibitor that differs from previous tyrosine kinase inhibitors (TKIs) in that it does not bind to the ATP-binding site of the kinase. Data from different clinical trials has shown an adequate safety and efficacy profile in chronic myeloid leukemia (CML) patients failing previous TKIs. However, no findings have been communicated in real life experience. The aim of our study is to present first results of asciminib in CML patients failing previous TKIs under the current compassionate use program. Methods: We retrospectively collected data from 31 patients treated with asciminib in 25 centers under compassionate use program. Data collecting was performed between October 2018 and June 2020. Patients baseline characteristics are shown in table 1. Most patients were heavily pretreated with 28 patients receiving 3 or more TKIs previous to asciminib. Eleven patients (35.5%) had been treated with ponatinib at some point throughout the disease. Twelve patients showed BCR-ABL1 mutations (only 1 case with T315I mutation). Switch to asciminib was due to intolerance in 22 patients and due to resistance in the remaining 9. Median dose of asciminib was 80mg per day (40mg every 12 hours). Treatment responses were evaluated according to European Leukemia Net recommendations. Data compilation and analysis were performed with REDCap Software and IBM SPSS (Version 25.0). Results: Median time on asciminib for the entire cohort was 35 weeks. Regarding toxicities, 13 patients (42%) experienced mild extra-hematological side effects (grade 1-2) being the most frequent fatigue (19%), joint pain (16%) and nausea (9%). Four patients (12,9%) showed severe (grade 3-4) extra-hematological events: fatigue, hepatotoxicity, hypertension and pericardial effusion (1 patient each). Three patients (9,7%) suffered from grade 4 thrombocytopenia, 2 of them associating grade 4 neutropenia. All toxicities according to previous TKIs adverse effects as well as cross-intolerance data is shown in table 2. Dose reduction had to be carried out in 9 patients (29%), 7 of those with temporary treatment interruptions; most owing to hematological adverse effects. In terms of efficacy (Graph 1), probability of reaching or at least maintaining previous response was 100%, 61.3% and 35.5% for complete hematological response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR), respectively. Regarding probabilities to improve previous responses, rates of CCyR and MMR were, respectively, 22,2% (2/9) and 22,2% (2/9) for resistant patients and 44% (4/9) and 62,5%. (10/16) for intolerant group. Amid the 11 patients previously treated with ponatinib, 3 patients (27,3%) showed improvement of response achieving at least MMR, 2 of them from the TKI-intolerant group and 1 from the TKI-resistant group. The median follow-up time was 40 weeks, after which 27 patients (87.1%) continued with asciminib. Treatment cessation happened in 2 patients due to progression to blastic phase and in 2 patients due to lack of efficacy. No patients discontinued due to side effects. Conclusion: The data presented, similar to that known from clinical trials, supports the use of asciminib in routine clinical practice in CML patients failing to previous TKIs. Disclosures Garcia-Gutiérrez: Novartis: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Incyte: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-138690

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

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detail.hit.zdb_id: 80069-7