Chronic Phase Pts Research Articles

Efficacy and safety of bosutinib in later-line patients (pts) with chronic myeloid leukemia (CML): A sub-analysis from the phase 4 BYOND trial.

e19055 Background: Bosutinib (BOS) is approved for pts with Philadelphia chromosome-positive CML resistant/intolerant to prior therapy and newly diagnosed pts in chronic phase. Methods: The BYOND trial (NCT02228382) evaluated the efficacy and safety of BOS in 163 pts with CML resistant/intolerant to prior tyrosine kinase inhibitors (TKIs; Gambacorti-Passerini et al, Blood, 2021). We report a sub-analysis of 48 pts treated with 2 (3L) and 3 (4L) prior TKIs, categorized by resistance/intolerance to the last received TKI. This sub-analysis is based on the final Nov 23, 2020 database lock. Results: There were 18 and 30 pts resistant or intolerant to the last TKI who entered the study without complete cytogenetic response (CCyR) or major molecular response (MMR), respectively. Median (range) treatment duration was 10.6 mo (1.6–48.5) vs 28.3 mo (0.2–48.6) and median (range) dose intensity was 447.1 mg/d (131.3–520.4) vs 288.8 mg/d (79.7–500.0) for resistant vs intolerant pts. Prior TKIs included imatinib (88.9% vs 100.0%), dasatinib (88.9% vs 83.3%), and nilotinib (66.7% vs 63.3%) for resistant vs intolerant pts. Overall, 61.1% vs 66.7% of resistant vs intolerant pts discontinued BOS, mostly commonly due to adverse events (AEs) in 27.8% vs 16.7% pts; 16.7% vs 6.7% discontinued BOS due to insufficient clinical response. Rates of CCyR/MMR are shown in the table. Among responders (resistant vs intolerant pts), median (range) time to CCyR was 5.1 mo (2.8–8.8) vs 3.0 mo (2.7–6.1); median (range) time to MMR was 5.8 mo (2.8–9.4) vs 3.2 mo (2.8–9.3). In resistant vs intolerant pts, any grade treatment-emergent AEs (TEAEs) were reported by 100.0% vs 96.7% pts; grade 3/4 TEAEs were reported by 72.2% vs 83.3% pts. Grade 3/4 TEAEs > 10% in resistant pts were thrombocytopenia (22.2%) and neutropenia (11.1%), and in intolerant pts were increased alanine aminotransferase (26.7%), diarrhea (23.3%), pleural effusion (13.3%), and rash (13.3%). Conclusions: This sub-analysis of resistant/intolerant pts without baseline CCyR or MMR shows BOS was active in heavily pretreated pts with resistance/intolerance to the last TKI. Despite a difference between resistant/intolerant pts, efficacy outcomes, though lower than the overall BYOND population, are encouraging, and safety was generally consistent with previous reports. Clinical trial information: NCT02228382. [Table: see text]

Vitamin D level and telogen hair loss: A Case control study

Abstract
 
 Background: Hair loss is a common skin condition. Hair is not a vital organ but losing it has a worse effect on the psychological state of the patient and may interrupt his daily social activities. Telogen effluvium founded to be the commonest noninflammatory cause to diffuse hair loss. Since nutritional disturbances are one of the triggering factors for it. It might be useful in the management of TE Due to the limited number of studies& little information is available on this subject possible role of vitamin D or its deficiency should be studied further.
 Aim of the study: to determine the association between Telogen effluvium and vitamin D level.
 Materials and methods: This is a case-control study performed in a period between December 2018 until June 2020; in Baghdad dermatology center at medical city. One hundred women who were seeking treatment for diffuse hair shedding and who hadn’t received treatment or supplements yet and One hundred fifty control subjects are chosen from patients who were referred to the dermatology clinic for the treatment of nevi and who are not pregnant or lactating, had no systemic or local scalp diseases are included in the study. Full History, physical examination performed for all cases including looking for cutaneous diseases, supplements & drug intake. Serum Vitamin D3 is measured using (Ichroma (TM), Boditech Med Inc., Korea).
 Result: A total of 250 females were included in this study, 100 of them got telogen effluvium & 150 were patients who attend dermatology clinic seeking treatments for nevi or skin tag (control group) .The mean age of cases was (22.59 ±4.837 year) that wasn’t significantly different from mean age of control group (23.647±6.022 years) (p-value =0.127). The mean level of Vitamin D was significantly lower than that of control group (11.16±4.49) Vs (18.98±10.65), P value <0.001. Vitamin D mean level in acute phase was significantly higher than that of chronic phase pts. (11.68±4.77 & 9.93 ±3.55 respectively), p value=0.04. Mean vit. D among symptomatic patients. (9.7 ± 3.5) was significantly lower than that among asymptomatic pts. (13±4.19) (p=0.001).No significant association were noticed between job & residence of the patients of both groups, (P-value =0.283 & 0.069 respectively (.
 Conclusion: Age mean difference was not significant among cases and controls. Deficiency in vitamin D may assume a possible leading cause of telogen effluvium among women with hair loss. Cases were significantly associated with low level of Vitamin D3 than controls.Low level of vitamin D was dominant among housewives, urban women, and among symptomatic patients with acute duration.

Comparison of Healthcare Resource Utilization and Costs Related to Infections between Patients Newly Diagnosed with Chronic Myeloid Leukemia Treated with Dasatinib and Nilotinib As First-Line Therapy in the United States

Introduction:In the past decade, targeted inhibition of BCR-ABL1 with tyrosine kinase inhibitor therapies (TKIs) has become the standard-of care for treatment of chronic myeloid leukemia (CML). Second-generation TKIs, including dasatinib and nilotinib, have been shown to be more effective treatment options over imatinib and are approved as first-line therapies for newly diagnosed patients (pts) with Philadelphia chromosome positive CML in chronic phase (CP) and as second-line therapies for pts in CP and accelerated phase resistant to or intolerant to prior therapy. Although TKIs have been demonstrated to prolong overall and progression-free survival, there is evidence that TKIs may be associated with an increased risk of infections. This risk of infections can occur with or without neutropenia and is potentially due to an immunosuppressive effect from off-target activity of the treatment (Reinwald 2016). The real-world healthcare resource utilization (HRU) and costs related to infections have not been well studied, particularly in pts diagnosed with CML treated with second generation TKIs. To address this gap, this study compared HRU and costs of pts receiving dasatinib or nilotinib in first-line therapy for CML, with a focus on infection-related economic outcomes.Methods:Adult pts newly diagnosed with CML who were initiated on dasatinib or nilotinib as first-line therapy on/after October 2010 were identified from 2 large US administrative claims databases (2006-2016). First-line TKI initiation was defined as the index date, the 6-month period before the index date was defined as the baseline period, and pts were observed from index date until the end of first-line TKI therapy (i.e., discontinuation, switch, end of data availability/continuous health plan enrollment). HRU, including inpatient (IP) days, emergency room (ER) visits, and days with outpatient (OP) services, and associated healthcare costs from a payers' perspective (USD 2016) were measured during first-line TKI therapy. All-cause HRU and costs and those related to infections of any type, identified using diagnosis recorded in medical claims, were compared between dasatinib and nilotinib pts using multivariate regression models.Results:A total of 1,156 dasatinib and 677 nilotinib pts met the sample selection criteria. Mean age was 52 years and 54% were male in both cohorts (p>.05). Mean TKI therapy duration was 13.6 months for dasatinib and 15.5 months for nilotinib (p=.014).On average, dasatinib pts had 2.7 all-cause IP days annually, where 1.4 (52%) were related to infections; nilotinib pts had 1.3 all-cause IP days annually, where 0.6 (46%) were related to infections. Dasatinib pts had 90% more all-cause IP days (adjusted IRR=1.9; p=.003) and 2 times more IP days related to infections (adjusted IRR=2.1; p=.020) than nilotinib pts (Figure 1). On average, dasatinib pts had 0.7 all-cause ER visits annually, where 0.2 (29%) were related to infections; nilotinib pts had 0.6 all-cause ER visits annually where 0.1 (16%) were related to infections. Dasatinib pts had 30% more all-cause ER visits (adjusted IRR=1.3; p=.041); 2 times more ER visits related to infections (adjusted IRR=2.1; p<.001) than nilotinib pts (Figure 1). On average, dasatinib pts had 27.5 days with all-cause OP services annually, where 1.6 (6%) were related to infections; nilotinib pts had 26.0 all-cause days with OP services annually where 1.5 (6%) was related to infections (difference not statistically significant).On average, the annual all-cause total cost was $157,767 for dasatinib pts with $37,110 (24%) for medical service costs and $120,657 (76%) for pharmacy costs. Of this total cost, $10,943 (7%) was related to infections. On average, the annual all-cause total cost was $136,290 for nilotinib pts with $24,508 (18%) for medical service costs and $111,782 (82%) for pharmacy costs. Of this total cost, $7,620 (6%) was related to infections. Dasatinib pts incurred higher all-cause total costs by $17,265 per patient per year compared to nilotinib pts (adjusted cost difference; p=.004); where $6,572 (38%) of the difference was related to infections (adjusted cost difference; p=.004; Figure 1). Overall, among pts with infection, the average cost related to infection during first-line TKI therapy was $9,637.Conclusion:Dasatinib was associated with higher HRU and healthcare costs, particularly related to infections, compared to nilotinib. [Display omitted] DisclosuresSeiter:Novartis: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau. Latremouille-Viau:Analysis Group, Inc.: Employment; Novartis: Other: Analysis Group, Inc. has received consulting fees from Novartis. Guerin:Novartis: Other: I am an employee of Analysis Group, which received consulting fees from Novartis; AbbVie Inc.: Other: I am an employee of Analysis Group, which received consulting fees from AbbVie ; Analysis Group, Inc: Employment. Ndife:Novartis Pharmaceuticals Corporation: Employment. Habucky:Novartis: Employment. Joseph:Novartis Pharmaceuticals Corporation: Employment; Pfizer: Other: stock/stock options; Amgen: Other: stock/stock options; Express Scripts: Other: stock/stock options. Pivneva:Analysis Group, Inc: Employment; Novartis: Other: Analysis Group, Inc. has received consulting fees from Novartis. Gagnon-Sanschagrin:Novartis: Other: Analysis Group, Inc. has received consulting fees from Novartis; Analysis Group, Inc.: Employment. Tang:Novartis: Employment, Equity Ownership.

Molecular Responses after Switching from a Standard-Dose Twice-Daily Nilotinib Regimen to a Reduced-Dose Once-Daily Schedule in Patients with Chronic Myeloid Leukemia: A Real Life Observational Study (NILO-RED)

IntroductionStandard dosing regimen for the BCR-ABL1 tyrosine kinase inhibitor (TKI) nilotinib in chronic myeloid leukemia (CML) is 300mg twice daily (BID) in the frontline setting and 400mg BID in the 2nd line setting or beyond. Patients (pts) are instructed to fast within 2 hours before and 1 hour after medication intake due to significant high-fat food effects on drug bioavailability. On-label dose adjustments to a lower-dose once-daily (QD) regimen are recommended solely in case of significant toxicity.Study goalThe primary aim of our observational two-center study was to ask whether nilotinib-treated adult CML pts were able to maintain major molecular responses (MMR) within 1 year after conversion to a more convenient nilotinib QD regimen at reduced doses, regardless of reasons for tapering nilotinib. Pts with minor transcripts or a history of blast crisis or allogeneic stem cell transplantation were excluded.PatientsEighty one pts in chronic phase were identified and included and results from the first 67 pts with a follow-up of at least 12 months after the switch to the once-daily dose-reduced nilotinib regimen are presented. Median age at study entry was 52 years (range: 19-82). There were 25 males (37.3%) and the Sokal score was low, intermediate, high or unknown in 43.3%, 37.3%, 13.4% and 6% of pts, respectively. All pts had major-type BCR-ABL1 transcripts. Nilotinib was started as 1st line TKI at 300mg BID in 68.6% of pts and as 2nd or subsequent line TKI at 400 or 300 mg BID in 31.4% of pts due to intolerance, warning, resistance or absence of a deep molecular response on prior therapy. Median duration of nilotinib prior switching to a reduced QD dosing was 29 months (range: 1-94) and median duration of MMR was 25 months (range: 3-212). Primary reason for the switch to a reduced QD nilotinib dosing was non-serious adverse events in 37.3% of pts and improvement in pts convenience in 62.7% of pts. Nilotinib was reduced down to 450mg QD, 400mg QD or 300mg QD in 86.6%, 10.4% and 3% of pts, respectively. A 2nd dose reduction from 450mg to 300mg QD was performed in 30 pts after a median time of 18 months (range: 4-37). The median duration of low-dose nilotinib QD was 24 months (5-54). No severe tolerance issues were encountered and no ischemic cardiovascular events occurred. Eleven pts stopped nilotinib due to treatment-free remission attempt (n=10) or persistent adverse event (n=1). All pts were alive at last follow-up.Evolution of molecular responsesAt baseline, the number of pts in MMR, MR4 and ≥MR4.5 was 9 (13.4%), 17 (25.4%) and 41 (61.2%), respectively and 32 pts (47.8%) had undetectable BCR-ABL1 transcripts. Median BCR-ABL1/ABL1 % IS was 0.006% (range: 0.0007-0.063) and median ABL1 copy number in pts with undetectable transcripts was 87259 (range: 36018-921339). Only 2 pts treated with 1st line nilotinib lost MMR 4 and 6 months after QD dose reduction of nilotinib with BCR-ABL1/ABL1 % IS at 0.13 and 0.11%, respectively. Both pts spontaneously regained MMR 4 months later without any treatment modification. Kaplan-Meier analysis of survival without unconfirmed MMR loss was 97% (95% CI: 92.9-100) at 12 months and analysis by molecular response category showed that none of the pts who were at least in MR4 at baseline lost MMR (Figure 1). At last follow-up on low-dose QD nilotinib, the number of pts in MMR, MR4 and ≥MR4.5 was 4 (6.3%), 11 (16.4%) and 52 (77.6%), respectively and 37 pts had undetectable transcripts (55.2%). Median BCR-ABL1/ABL1 % IS was 0.0035% (range: 0.00025-0.058) and median ABL1 copy number in pts with undetectable transcripts was 96000 (range: 23285-472000).Ten pts in long-lasting deep molecular response stopped nilotinib without further treatment after a median duration of TKI and of nilotinib of 60 months (range: 50-149) and 56 months (range: 42-87), respectively. Their follow-up after nilotinib discontinuation was 18 months (range: 5-33). Only 1 of them lost MMR and restarted therapy 5 months later while the others remained treatment-free.ConclusionSwitching to a nilotinib QD regimen at reduced doses as maintenance therapy after achievement of a MMR on standard-dose nilotinib BID schedule is feasible and safe in chronic phase CML pts regardless of prior treatment history and does not compromise the anti-leukemic efficacy of nilotinib. Our results may pave the way for clinical trials aiming at systematic avoidance of overtreatment and improvement of pts convenience in treatment with nilotinib. [Display omitted] DisclosuresRea:Pfizer: Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Honoraria. Cayuela:BMS: Honoraria; Novartis: Honoraria. Etienne:BMS: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Consultancy, Research Funding.

Integrative Genomics Reveals Cancer Associated Mutations Are Common at Diagnosis of CML in Patients with Poor Response to TKI Therapy

Integrative Genomics Reveals Cancer Associated Mutations Are Common at Diagnosis of CML in Patients with Poor Response to TKI Therapy

Outcomes before and after dose reduction in patients with newly diagnosed chronic myeloid leukemia receiving bosutinib or imatinib.

7039 Background: Bosutinib (BOS) is approved for patients (pts) with Philadelphia chromosome-positive chronic myeloid leukemia (CML), at a starting dose of 400 mg QD in newly diagnosed pts in chronic phase (CP). This analysis evaluated the impact dose reduction has on the outcomes of BOS and imatinib (IMA) in pts with CP CML. Methods: In the open-label BFORE trial, 536 pts with newly diagnosed CP CML were randomized to receive 400 mg QD BOS (N = 268) or IMA (N = 268; 3 untreated). Dose could be reduced to 300 mg QD for toxicity. Following sponsor approval, dose reduction to BOS 200 mg QD was permitted for 4 wks maximum; after this time, dose escalation or treatment discontinuation was required. Maintenance of response after dose reduction was defined as having a response &gt; 6 mo after the first reduction. Database lock: June 12, 2020, 5 y after the last pt enrolled. Results: In the BOS arm, dose reduction to 300 (without further reduction) or 200 mg QD was seen in 82 (31%) and 33 (12%) pts, and median time to dose reduction was 85 and 205 d. In the IMA arm, 50 (19%) pts had a dose reduction to 300 mg QD, and median time to dose reduction was 92 d. Most common (≥2% of pts) treatment-emergent adverse events (TEAEs) leading to dose reduction were increased alanine aminotransferase (8%), thrombocytopenia (7%), diarrhea (7%), increased lipase (6%), increased aspartate aminotransferase (4%), nausea (4%), neutropenia (3%), rash (3%) and abdominal pain (2%) with BOS, and neutropenia (4%) with IMA. Of the pts who remained on 400 mg QD BOS (n = 153) or IMA (n = 214), respectively, 120 (78%) and 139 (65%) achieved major molecular response (MMR). Among pts who had a BOS dose reduction to 300 mg QD, 51/82 (62%) had MMR &gt; 6 mo after dose reduction: 14 (17%) maintained MMR before and after dose reduction and 37 (45%) achieved MMR for the first time after dose reduction. Seven (9%) pts had MMR before dose reduction but discontinued treatment before the next &gt; 6 mo assessment. In the IMA arm, 32/50 (64%) pts had MMR &gt; 6 mo after dose reduction: 9 (18%) maintained MMR before and after dose reduction and 23 (46%) achieved MMR for the first time after dose reduction. One (2%) pt had MMR before dose reduction but discontinued treatment before the next &gt; 6 mo assessment and 1 (2%) pt lost a previously attained MMR after dose reduction. Among pts who had a BOS dose reduction to 200 mg QD, 12/33 (36%) had MMR &gt; 6 mo after dose reduction: 7 (21%) maintained MMR before and after dose reduction and 5 (15%) achieved MMR for the first time after dose reduction. Six (18%) pts had MMR before dose reduction but discontinued treatment before the next &gt; 6 mo assessment. Similar trends were seen for complete cytogenetic response. Conclusions: Management of TEAEs through BOS or IMA dose reduction enabled pts to continue treatment, with a substantial number of pts achieving MMR for the first time after dose reduction. Clinical trial information: NCT02130557.

Ruxolitinib Rechallenge in Resistant/Intolerant MF Patients: Frequency, Therapeutic Effects, and Impact on Outcome

Ruxolitinib Rechallenge in Resistant/Intolerant MF Patients: Frequency, Therapeutic Effects, and Impact on Outcome

Prevalence of Sars-Cov-2 Infection in Patients with Chronic Myeloid Leukemia

Background:The new SARS-CoV-2-induced disease (COVID-19) pandemic has represented a huge challenge for the health systems and has been responsible for almost 700.000 deaths worldwide as of 1st August 2020. Older age, male sex, comorbidities, ethnicity and socioeconomic factorsare risk factors for severe COVID-19. While the direct effect of solid cancer on the COVID-19 outcome has been investigated and is still debated, limited information is available on the impact of an underlying hematological malignancy on the risk of contracting SARS-CoV-2, the clinical presentation and the outcome of the infection.We report on the prevalence of SARS-CoV-2 infection in a large cohort of patients (pts) with chronic myeloid leukemia (CML).Methods:We retrospectively investigated the exposure to SARS-CoV-2 through serological testing in a single centre cohort of CML pts. Of more than 600 pts on active follow-up, we have screened 161 pts between 1st June and 27th July 2020. At each consultation, we recorded any exposure to or symptoms of SARS-CoV-2 infection in the preceding 6 months.The Imperial Hybrid DABA, a two-step double antigen binding assay (DABA) for the detection and measurement of total antibody directed to the receptor binding domain (RBD) of SARS-CoV-2 was used for analysis. The cut-off (CO) for positivity is established by adding 0.1 to the average of optical density (OD) obtained for the negative controls. A sample-OD/cut-off (S/CO) value ≥ 1 is considered reactive.Results:161 CML pts in chronic phase underwent serological testing (median age 54 years (18-92), male n=94). Twenty pts were off TKI (post-alloSCT, n=12; in treatment free remission n=6; pregnancy=1 and intolerance n=1) and 141 were on active treatment (imatinib [n=41], dasatinib [n=38], nilotinib [n=23], bosutinib [n=21], asciminib [n=11], ponatinib [n=6] and K0706 [n=1]). The ethnic distribution was White (n=119), Asian-Indian (n= 24), Asian-Chinese (n=3), Black (n=9), Arab (n=5), Mixed Asian-White (n=1).Eighteen pts (11.2%) have tested positive (Table 1). Thirty-eight pts (23.6%) reported symptoms compatible with COVID-19 of whom 12 (31.6%) were DABA positive. Six of 123 (4.9%) asymptomatic pts also tested positive. The time from onset of symptoms to the date of testing were similar in both seropositive (105 days, range 56-180) and seronegative pts (100 days, range 21-205). The median S/CO ratio was 9.9 (1-23.3) in the symptomatic and 1.5 (1.2-21.4) in the asymptomatic pts.Among the 18 positive pts, the median age at symptom presentation was 54 years (38-75) and 12 were males. The median time from CML diagnosis was 7.6 years (0.2-20) and two pts were post-alloSCT. Ethnicity was White, Asian-Indian, Black in 8 (44.4%), 6 (33%) and 4 (22.2%), respectively.In 15 pts (83.3%) symptoms were absent or mild, moderate in 2 and severe in one patient 2 years post-alloSCT on continuing immunosuppression for GvHD. Only 2/18 had PCR tests for SARS-CoV-2 at the time of infection and both were positive. Of the 16 pts not tested for antigen, 2 had been in close contact with a family member with a PCR-confirmed SARS-CoV-2 infection. In the mild cases, the most frequent symptoms were fever (n=7) and cough (n=6), followed by fatigue (n=2), myalgia (n=2) and anosmia (n=2). One patient presented only with acute limb ischemia, derived from thrombus in the superficial femoral artery. One patient had radiological features of COVID-19 pneumonia, but did not require hospitalization. The only patient with severe COVID-19 developed pneumonia requiring CPAP, was refractory to tocilizumab (anti-IL6), but recovered after starting ruxolitinib (JAK2-inhibitor). The median time to complete resolution of symptoms was 21 days (7-56).Conclusions:The prevalence of infection in our CML pts is similar to that of the overall population, which suggests that they are capable of mounting appropriate antibody response against SARS-CoV-2.Importantly, in seropositive pts symptoms were mild. Of note is the higher prevalence in the BAME community and underlines the potential role of socioeconomic factors in disease transmission. Expansion of this CML cohort and serial antibody testing in seropositive patients will provide further information regarding prevalence and durability of serological responses.DisclosuresMilojkovic:Incyte: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Apperley:Bristol Myers Squibb: Honoraria, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.

CML-266: Second Generation Tyrosine Kinase Inhibitors in First Line Can Reduce the Time to Treatment-Free Remission in Chronic Myeloid Leukemia Patients

Introduction Duration of treatment with tyrosine kinase inhibitors (TKI) is an important favorable prognostic factor for treatment-free remission (TFR) and deep molecular response (DMR) in patients (pts) with chronic myeloid leukemia (CML). Aim To analyze the impact of first-line treatment duration with imatinib and 2G TKI on molecular relapse-free survival (MRFS) in CML pts with sustained DMR. Patients and methods In total, 174 CML pts in chronic phase with ≥3 years treatment duration and sustained DMR (MR4-MR5, BCR-ABL IS 0.1%). Median (Me) age of pts was 43 (range 21-86) years; 39% were males. Me TKI treatment duration was 86 months (IQR 57-125 mo), Me DMR duration was 45 (IQR 29-66 mo). Imatinib, 2G TKI in first-line and 2G TKI in second-line were discontinued in 116 (66.7%), 15(8.6%) (11 nilotinib, 3 dasatinib, 1 bosutinib) and 43 (24.7%) (34 nilotinib, 9 dasatinib) pts respectively. Results Me follow-up time after treatment cessation was 33 months (range 1-133). MRFS at 6, 12, 24 and 36 months was 62% (CI: 55-70%), 53% (CI: 45-60%), 50% (CI: 42-57%) and 48% (CI: 40-56%) respectively. Treatment duration and MR4.5 vs MR4 were significant for MRFS both in univariate (p=0.009 and p=0.015) and multivariate analysis (p=0.017 and p=0.037). No difference in 36 months MRFS was observed for imatinib (47% (CI: 42-60%)), first-line 2G TKI (59% (CI: 33-84%) p=0.58) and second-line 2G TKI (47% (CI: 32-63%) p=0.97) groups. However, significantly shorter treatment duration was observed in first-line 2G TKI group (Me=44 mo (IQR 40-52 mo)) vs imatinib (Me=93 mo (IQR 69-127 mo)), p Conclusion The 2G TKI as a first-line seem to be an effective option to reduce the treatment duration before TFR in CML pts although MRFS rate was not significantly improved in our study.

Bosutinib in patients with chronic phase chronic myeloid leukemia intolerant to prior tyrosine kinase inhibitors: Analyses from the BYOND study.

7551 Background: Bosutinib (BOS) is approved for patients (pts) with Philadelphia chromosome (Ph)+ chronic myeloid leukemia (CML) resistant/intolerant to prior therapy and in newly diagnosed pts in chronic phase (CP). Methods: The ongoing phase 4 BYOND study is further evaluating efficacy and safety of BOS (starting dose 500 mg/d) for CML resistant/intolerant to prior tyrosine kinase inhibitors (TKIs). We report findings in pts intolerant to all prior TKIs. Data are reported ≥1 y after the last enrolled pt (~85% TKI-intolerant pts had ≥2 y follow-up). Results: Of 163 pts who received BOS, 156 had Ph+ CP CML. 73 pts entered the study due to intolerance; 29, 26 and 18 had 1 (CP2L), 2 (CP3L) and 3 (CP4L) prior TKIs, respectively. After a median follow-up of 30.4 mo, median treatment duration across all 3 cohorts (CP2L, CP3L, CP4L, respectively) was 25.3 mo (29.2, 24.6, 17.6) and median dose intensity was 292.0 mg/d (304.5, 284.8, 272.1). Across CP CML cohorts (CP2L, CP3L, CP4L, respectively), 84.9% of patients (82.8%, 88.5%, 83.3%) had ≥1 dose reduction and 83.6% (79.3%, 84.6%, 88.9%) had ≥1 dose interruption due to adverse events (AEs). At the data cutoff, 53.4% (CP2L 65.5%, CP3L 42.3%, CP4L 50.0%) were still receiving BOS. The most common reason for discontinuation was AEs (28.8%). The most common ( &gt; 40%) treatment-emergent AEs (TEAEs) were diarrhea (87.7%) and nausea (43.8%). Grade 3/4 TEAEs in &gt; 10% of pts were diarrhea (16.4%), increased alanine aminotransferase (19.2%) and increased lipase (12.3%). Most pts with a valid baseline assessment achieved major molecular responses (MMR) across therapy lines (Table). Deaths occurred in 4 pts (CP2L 1, CP3L 3, CP4L 0); none were related to BOS or CML. Overall survival rate (95% CI) at 2 y in TKI-intolerant pts was 97.2% (89.2–99.3); rates were 96.4% (77.2–99.5), 96.0% (74.8–99.4) and 100% (100–100) in CP2L, CP3L and CP4L pts, respectively. Conclusions: A long duration of treatment and high response rate were observed in TKI-intolerant pts treated with BOS. Despite being intolerant to all prior therapies, ≥50% of pts in the overall intolerant cohort remained on BOS treatment at the data cutoff and &gt; 80% achieved/maintained MMR. These results further support BOS use in pts with Ph+ CP CML and intolerance to all prior TKIs. Clinical trial information: NCT02228382 . [Table: see text]

Effectiveness of Bosutinib in Chronic Myeloid Leukemia (CML) Who Have Received Multi Tyrosine Kinase Inhibitors (TKIs)

Effectiveness of Bosutinib in Chronic Myeloid Leukemia (CML) Who Have Received Multi Tyrosine Kinase Inhibitors (TKIs)

Aurora Kinase a/MDM2-Mediated SETD2 Loss of Function in Chronic Myeloid Leukemia Patients in Blast Crisis Can be Therapeutically Targeted Inducing Apoptotic Cell Death in a Caspase-Dependent Way

Aurora Kinase a/MDM2-Mediated SETD2 Loss of Function in Chronic Myeloid Leukemia Patients in Blast Crisis Can be Therapeutically Targeted Inducing Apoptotic Cell Death in a Caspase-Dependent Way

Involvement of RUNX1 Pathway Is a Common Event in the Leukemic Transformation of Chronic Myeloproliferative Neoplasms (MPNs)

Introduction. Runt-related transcription factor 1 (RUNX1) is a transcription factor critical for normal and leukemic hematopoiesis. Three main isoforms, RUNX1 i-1a, i-1b and i-1c, are produced through alternative splicing of RUNX1. Unlike i-1b and i-1c, i-1a has a Runt homology domain (RHD) but lacks the transactivation domain (TAD), and inhibits transcriptional activity of -1b by competing with higher affinity for target gene sequences. Overexpression of i-1a in cell lines inhibits terminal myeloid differentiation. The i-1a is expressed at high levels in patients (pts) with acute myeloid leukemia (AML). Mutations of RUNX1 are common in CMML and MDS, whereas incidence and clinical correlates of RUNX1 mutations in MPNs are poorly known. Aim: To analyze the spectrum and clinical correlates of RUNX1 genetic abnormalities (RUNX1-abn), and the expression of RUNX-1a isoform, in a large series of pts with MPNs. Methods. 686 MPN pts (50 PV, 165 ET, 154 overt-PMF, 143 prefibrotic-PMF, 74 PPV-MF and 100 PET-MF, diagnosed according to 2016 WHO) were included in the study; of these, 625 were analyzed in chronic phase (CP) and 61 at leukemic transformation (LT; of a total of 106 LTs, 58%), including 29 cases with paired samples at diagnosis and LT. Established methods were used for JAK2, MPL and CALR genotyping. A high molecular risk (HMR) category was defined according to Vannucchi A, [Leukemia 2013]. Ion Torrent NGS platform was used to genotype all RUNX1 coding sequence. In 21/29 paired samples, a long reads genome sequencing by Oxford Nanopore technology (ONT) was performed. Copy number variation (CNV) analysis was performed with NanoGLADIATOR package [Magi A, Genome Biol 2019]. Differential expression of RUNX1 mRNA isoform1a and 1b was analyzed by qRT-PCR. Nonparametric Wilcoxon rank-sum test, Kaplan-Meier estimates and log-rank test were used as appropriate. Results. Somatic RUNX1 mutations were identified in 31 pts (4.5%): 14/625 in CP (2.2%) and 17/61 in LT (27.9%; P&lt;.0001); 7/17 LT pts (41.1%) had two variants. 10/29 paired samples were RUNX1 mutated, in 8 of which mutations were acquired at LT. All mutations were heterozygous (median VAF 40%, range 0.4%-54%); 13 (34.2%) were frameshift, 5 (13.2%) nonsense and 20 (52.6%) missense. Most mutations clustered in RHD (26/38, 68.4%) and TAD (9/38, 23.7%). CNV involving RUNX1 was detected by ONT in 4/21 (19%) paired samples, including 2 gain and 2 loss, all acquired at LT; 2 pts had concurrent RUNX1 mutation. Overall, RUNX1abn, inclusive of mutations and CNV, occurred in 19/61 (31.1%) patients at LT. RUNX1-abn were more common in MPL (12.5%) and TN (7.5%) pts compared with JAK2 (4.3%) and CALR (2.0%) mutated (P=0.04), and were enriched in HMR category (61.3% vs 29.4% vs pts without RUNX1-abn; P=.001). We also analyzed CNV in a total of 47 selected genes included in the RUNX1 pathway (KEGG Orthology K08367); we found CNV in &gt;1 of these genes in 16/21 (76%) pts at LT vs 2/16 (12.5%) of CP pts. After median follow-up of 4.9y (range 0.1-36.2y) 273 pts died (39.8%). 106 pts (15.4%) progressed to AML after median of 4.7y (0.1-36.2y) from diagnosis. Incidence of LT differed significantly among diseases: 3 pts in PV (5.9%), 17 in ET (10.1%), 39 in overt-PMF (23.5%), 12 in prefibrotic-PMF (8.3%), 11 in PPV-MF (14.1%) and 24 in PET-MF (22.6%). RUNX1-abn were detected, respectively, in 100%, 53.0%, 23.1%, 41.7%, 36.4% and 12.5% of cases at either CP and/or LT. Leukemia-free survival (LFS) was shorter in pts harboring RUNX1-abn in CP compared to RUNX1-WT pt (2.8y vs NR; P&lt;.0001)(Fig 1A). Expression levels of i-1a and -1b were measured in 34 CP and 24 LT pts. Isoform-1a was significantly elevated in LT pts (mean 7.51±10.1) compared to CP (1.12±1.75; P=.009) (Fig 1B; lines represent the i-1a level rise from CP to LT in 4 paired samples). The i-1a expression levels were irrespective of RUNX1 mutated (mean 7.6±11.9) or unmutated (mean 9.2±6.3) status in LT pts (P=0.8). No difference of i-1b levels in CP (mean 0.9±0.7) versus LP (mean 1.6±1.4; P=0.08) was observed. The expression of i-1a was not dependent on gender, age, leukocyte or platelet count, hemoglobin and percentage of blast cells. Conclusions. These findings indicate that most MPN pts with LT have involvement of RUNX1 pathway through different mechanisms (mutations, CNV, altered isoform expression, genomic abnormalities of RUNX1 target genes), suggesting that a "RUNX1pathy" may represent a common event during leukemogenesis in MPNs. Figure 1 Disclosures Vannucchi: CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees.

PF674 OUTCOME OF PATIENTS WITH MYELOFIBROSIS AFTER RUXOLITINIB DISCONTINUATION: ROLE OF DISEASE STATUS AND TREATMENT STRATEGIES IN 218 PATIENTS

Background:After discontinuation of Ruxolitinib (RUX), the outcome of patients (pts) with myelofibrosis (MF) has been reported to be poor.Aims:Here, we investigated the impact of baseline features, responses, and type of salvage therapy on survival in 218 pts who received and discontinued RUX in routine clinical practice.Methods:A clinical database was created in 20 European Hematology Centers including retrospective data of 521 MF pts treated with RUX from Jan 2011 to October 2018. Spleen/symptoms response to RUX were evaluated according to the 2013 IWG‐MRT/ELN criteria. Overall (OS) was estimated from the date of RUX discontinuation to the date of death or last contact (log‐rank test). Comparisons of continuous or categorical variables between groups were carried out by Wilcoxon‐Mann‐Whitney rank‐sum test or χ2, respectively. Risk factors for RUX discontinuation and prognostic factors for survival were identified using Cox proportional hazards model.Results:After a median follow‐up from RUX start of 37 months, 268 out of 521 (51.2%) pts stopped RUX, with a discontinuation rate of 19.6 per 100 patient‐years. Intermediate‐2/High DIPSS risk score, platelet count &lt;100 x109/l, Charlson Comorbidity Index ≥2 and unfavorable karyotype were significantly associated with a higher probability of drug interruption. Fifty pts (18.7%) died while taking RUX; median survival time of the remaining 218 pts after RUX stop was 13.2 months. Causes of RUX discontinuation in the 218 pts were: lack (22.9%) / loss (11.9%) of response, progression to blast phase (23.4%), toxicity (28.9%; specifically anemia [10.5%], thrombocytopenia [6.9%], infections [9.2%], other adverse events [2.3%]), second solid neoplasia (4.6%), and thrombosis (3.2%). 11 pts (5.1%) stopped RUX while in response and underwent allogeneic stem cell transplantation (alloSCT). Compared to the 256 pts still on treatment at last contact, the 218 pts who discontinued RUX had started the therapy with a significantly more advanced disease in terms of higher DIPSS risk score, larger splenomegaly, and deeper cytopenias. Previous response to RUX did not influence OS. OS was significantly influenced by disease status (chronic vs blast phase) but not by reason of discontinuation (resistance vs intolerance) (Fig. 1a). A total of 167 pts discontinued RUX in chronic phase (CP) and had a median survival after discontinuation of 27.5 mos. In this cohort, hemoglobin&lt;10 g/dl (p = 0.01) and a circulating blasts ≥1% (p = 0.01) at the time of RUX withdrawal correlated with worse survival. 111 CP pts (66.5%) received a salvage therapy that included JAK2‐inhibitors and/or other investigational agents in 31 cases and only conventional medical therapies in 54; 26 pts underwent alloSCT after conventional therapies. Pts treated with novel agents had a significantly better OS (Fig. 1b). 51 (23.4%) pts discontinued RUX in BP, and 28 (54.9%) received salvage treatments including hydroxyurea (n. 14), hypometylating agents (n. 7), chemotherapy (n. 6), alloSCT (n. 5). Median survival time was significantly higher for pts who received therapy after RUX (7.9 mos vs 2.2 in untreated pts, p = 0.005).Summary/Conclusion:A greater burden of disease at RUX start is significantly associated with higher discontinuation rate. After RUX stop, outcome is mostly influenced by disease phase and type of salvage therapies, with CP pts treated with novel agents having the best outcome. Earlier RUX therapy and innovative salvage strategies may improve outcome of MF pts.image

Primary results of the phase 4 BYOND study of bosutinib (BOS) for pretreated chronic phase (CP) chronic myeloid leukemia (CML).

7012 Background: The tyrosine kinase inhibitor (TKI) BOS is approved for patients (pts) with Philadelphia chromosome (Ph)+ CML resistant/intolerant to prior therapy and newly diagnosed pts in CP. Methods: The ongoing phase 4 BYOND study is further evaluating efficacy and safety of BOS (starting dose 500 mg/d) for CML resistant/intolerant to prior TKIs. Primary endpoint (not powered) in Ph+ CP CML cohorts is cumulative confirmed major cytogenetic response (MCyR) by 1 y. Results: Of 163 pts who received BOS, 156 had Ph+ CP CML (46, 61 and 49 after 1, 2 and 3 prior TKIs, respectively). Across Ph+ CP CML cohorts, 51.9% of pts were male; median age was 61 y. As of 1 y after last enrolled pt (median follow-up 30.4 mo), 56.4% remained on BOS. Median BOS duration was 23.7 mo and median dose intensity after adjustment due to adverse events (AEs) 313 mg/d. Of 144 evaluable pts with a valid baseline assessment, cumulative confirmed MCyR by 1 y was 71.5% (95% confidence interval [CI] 63.4–78.7). Cumulative complete cytogenetic response rate anytime on treatment was 81.3% (95% CI 73.9–87.3). Cumulative molecular response (MR) rates were high across lines of therapy (Table). 10 deaths occurred (5 on treatment); 1-y overall survival rate was 98.0%. No pt progressed to accelerated/blast phase on treatment. 25.0% discontinued BOS due to AEs and 5.1% due to insufficient response. Most common treatment-emergent AEs (TEAEs) were diarrhea (87.8%) and nausea (41.0%). Grade 3/4 TEAEs in &gt; 10% of pts were diarrhea (16.7%) and increased alanine aminotransferase (ALT; 14.7%). The only TEAE leading to discontinuation in &gt; 5% of pts was increased ALT (5.1%). Conclusions: Most pretreated pts with Ph+ CP CML had MCyR by 1 y with BOS; a substantial proportion achieved or preserved major MR (MMR) and deep MR in all therapy lines. Results further support BOS use for Ph+ CP CML resistant/intolerant to prior TKIs. Clinical trial information: NCT02228382. [Table: see text]

Quality of Life in Chronic Myeloid Leukemia Patients with Deep Molecular Response Who Stopped Therapy By Tyrosine Kinase Inhibitors: Interim Results of Russian Prospective Multicenter Trial RU-SKI

BackgroundIt is reasonable to incorporate quality of life (QoL) assessment into the comprehensive evaluation of treatment outcomes in chronic myeloid leukemia (CML) patients (pts) with deep molecular response (DMR) who enter the treatment-free remission (TFR) phase and stop therapy by tyrosine kinase inhibitors (TKIs). QoL assessment was included into the design of Russian prospective multicenter trial RU-SKI along with the clinical outcomes evaluation.AimTo study QoL in chronic phase (CP) CML pts with DMR before stopping TKI treatment and during TFR observation.Materials and methodsThe study has been conducted within the clinical approbation supported by the Ministry of Health of RF. The CML CP pts with therapy by any TKI ≥ 3 years (yrs) and stable DMR (BCR-ABL ≤0.01% IS) during ≥2 yrs were enrolled. Pts who met these criteria and had previous resistance to any TKI were also eligible. TKIs were resumed in case of major molecular response loss (MMR, BCR-ABL>0,1%). The QoL questionnaires RAND SF-36 and EORTC QLQ C30 were filled out by the pts before stopping TKI treatment and at 1, 3, 6 and 12 months (mo) after treatment discontinuation. The comparison group consisted of healthy persons matched by age and gender to CML CP pts (n=97). The Mann-Whitney test, paired Wilcoxon test and Generalized Estimation Equations (GEE) with adjustment to age, gender, the risk group according to Sokal score and duration of TKI treatment were used for the statistical analysis.ResultsQoL assessment was performed in all 99 CML CP pts who were enrolled into the trial during a period from Aug 2015 till Dec 2017. The TKIs before treatment cessation were as follows: imatinib and second-generation (2G) TKIs were used in 69(70%) and 30(30%) pts accordingly. 2G TKIs were used in 9(30%) and in 21(70%) pts as 1st and 2nd line accordingly. Mean age was 47±14.5 yrs, 48.5% were males, 12.1% had high Sokal risk score. The physical functioning of CML pts before stopping TKI treatment compared to the healthy controls was significantly worse (p<0.05). Other QoL scales before stopping TKI treatment were slightly worse with no statistically significant difference compared to healthy controls (figure 1). MMR was lost in 45 pts, and was maintained in 54 pts, Me follow-up time after TKI stop was 14,9 mo (range 2,5-32). The significant improvement of role physical functioning and role emotional functioning was found (p<0.05) in pts who maintained stable MMR during 12 mo after TKI discontinuation. The Integral QoL Index increased from 0,58 to 0,72 (p<0,001) in these pts. The decreasing of nausea/vomiting, diarrhea, shortness of breath at different time points (p<0.05) during TFR was revealed (figure 2). The QoL and symptoms before TKI interruption and after reinitiating of TKIs in 45 pts who resumed treatment were similar. The Integral QoL Index before and after stopping TKI treatment was 0.62 vs 0.64 (p>0.05).ConclusionThe QoL in CML CP pts with DMR on TKI treatment is slightly worse and physical functioning is significantly lower as compared to healthy controls. The positive changes of the role functioning along with TKI treatment-related symptoms decrease were revealed in pts who maintained stable MMR during 12 mo of TFR. No changes in QoL and no new symptoms were found in pts who reinitiated treatment before and after TKIs interruption. The results of QoL assessment may contribute to optimization of the treatment strategies of CML patients with DMR. [Display omitted] DisclosuresChelysheva:Fusion Pharma: Other: provided consultations ; Bristol Myers Squibb: Other: provided consultations and performed lectures; Novartis: Other: provided consultations and performed lectures. Shukhov:Bristol Myers Squibb: Other: provided consultations and performed lectures ; Novartis: Other: provided consultations and performed lectures . Turkina:Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations. Ionova:Takeda: Research Funding; BMS: Research Funding.

Social Parameters Are Independent Predictors for Survival in Chronic Myeloid Leukemia

Introduction and data: Social and demographic personal data are important to be included in analysis and interpretation of results of any population studies in oncology. But it looks like social status is underestimated as cofounder for survival of patients with chronic myeloid leukemia (CML). The aim of this study was to check the prognostic value of social parameters like marital status and education level in comparison with standard risk factors. Russian CML Registry include more than 10 thousand patients (pts) data. In the analysis 8326 CML pts in chronic phase (CP) with first line TKI therapy were included: 91% of pts were treated by Imatinib and 9% by other TKIs. Mean age was 49years, 4607 f/ 3705 m. Me of follow-up-4.24years. Overall survival(OS) was estimated starting the diagnosis date, event was death from any reason, date of last contact was censored for alive pts. Survival analysis was performed by SAS procedures. Results:Firstly, we perform one-way survival analysis and estimate OS depending upon the 3 parameters Sokal Score, Marital Status and Education. There are high significant dependences OS on all three factors as shown on picture 1 (OS estimates depending on values of: 1A) Sokal score (low, intermediate, high), 1B) Marital Status (married, single, widowed/divorced), 1C) Education (low/secondary, higher). Marital Status and Education are correlated with Sokal Score (corresponding Pearson's coefficients are 0.19 and 0.12, p<0.0001). This association is caused by age but is not so strong. Than we have estimate OS in each Sokal's risk groups (picture 2. OS estimates depending on Marital Status (single, married - blue line, widowed/divorced - green line) in different Sokal's risk groups: 2A) - low, 2B) - intermediate, 2C) - high). OS estimates depending on Education (picture 3; (low/secondary red line, higher- blue line) in different Sokal's risk groups: 3A) low, 3B) intermediate, 3C) high. And we see that Marital Status and Education are predictive in each risk group but the most influent in high risk group. Marital Status and Education are correlated with other impotent cofounder- age. It should be checked in additional multi factor analysis we plan to do. We also run the proportional risk regression Cox's model on this data. Hazard ratio (HR) and significance (Px2) for included parameters are following: Sokal score - HR=1.59, Px2<0.0001; Education- HR=1.76, Px2<0.0001; Marital Status- HR=1.40, Px2<0.0006. Conclusions: The social and demographic personal data should be included in any analysis of CML population data. Marital Status and Educationare obviously associated with adherence behavior of CML patients and must influent on longitude therapy output. The highly education level is favorable factor, widowed/divorced marital status is unfavorable factor for OS prognosis. [Display omitted] DisclosuresKulikov:Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Turkina:Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations.

Outcome of Patients with Myelofibrosis after Ruxolitinib Failure: Role of Disease Status and Treatment Strategies in 214 Patients

Outcome of Patients with Myelofibrosis after Ruxolitinib Failure: Role of Disease Status and Treatment Strategies in 214 Patients

Prognostic Value of Clonal Evolution at the Time of Diagnosis in Patients with Chronic Myeloid Leukemia Treated with Frontline Tyrosine Kinase Inhibitors

Introduction:Additional cytogenetic clonal evolution (CE) is a known risk factor for a poor prognosis in chronic myeloid leukemia (CML). However, its prognostic significance in the setting of new tyrosine kinase inhibitor (TKI) remains unclear. We sought to analyze the baseline characteristics and clinical outcome in chronic phase (CP) CML pts with or without CE treated on frontline TKI clinical trials in a single institution.Methods:Patients (pts) with Ph-positive CML in CP with or without CE at the time of diagnosis receiving initial therapy with imatinib 400 mg/d, imatinib 800 mg/d, dasatinib 100 mg/d, nilotinib 800 mg/d or ponatinib 30 or 45 mg/d in consecutive or parallel clinical trials at a single institution were analyzed. Overall survival (OS), transformation free survival (TFS), event free survival (EFS), failure free survival (FFS) were analyzed from the start of therapy by Kaplan-Meier method. Clonal evolution (CE) was defined by the presence of any cytogenetic abnormality other than a single Ph, variant Ph chromosome or loss of Y chromosome. Also we analyzed CML pts with CE with regard 'major route' abnormalities vs other. The major route abnormalities includes trisomy 8 (+8), trisomy 19 (+19), isochromosome 17q10 (i17q) and additional Ph chromosome.Results:A total of 603 pts were analyzed including 579 pts in CP without CE and 24 pts with CE. Pts in CP without CE received initial therapy with imatinib-400 (n=70), imatinib-800 (n=200), dasatinib (n=138), nilotinib (n=122), or ponatinib (n=49), and pts with CE received imatinib-400 (n=2), imatinib-800 (n=7), dasatinib (n=10), nilotinib (n=4), and ponatinib (n=1). Pts with CP were usually older, female and have a higher WBC (P < 0.001). There was a statistically significant higher Complete cytogenetic response (CCyR) at 6 mo in pts without CE (P = 0.012), however the cumulative and 3-month rates of complete hematologic response (CHR), and the cumulative rates of CCyR and MMR were not different (Table). Similarly, the rates of MR4.0 and MR4.5 were similar for the two groups. At 5 years, the presence of additional cytogenetic findings at diagnosis does not seem to affect the rate of transformation, failure-free, event-free and overall survival. Acknowledging the small sample size for subset analysis, response rates and survival outcomes were comparable in CP with CE irrespective of whether chromosomal abnormalities were ’major route’ or other (n=12 in each arm).Conclusion:Additional cytogenetic CE at the time of diagnosis among patients with CML in CP is associated with a similar favorable outcome as those without CE when treated with TKI. The type of additional CE (major route vs other) does not seem to impact outcome. Patients with CML-CP with CE at the time of diagnosis can thus be treated with TKI as all other pts with CP with no need for consideration for SCT unless there is clear evidence of failure. DisclosuresJabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Ravandi:BMS: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. DiNardo:Abbvie: Research Funding; Agios: Other: advisory board, Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding; Novartis: Other: advisory board, Research Funding; Celgene: Research Funding. Daver:Ariad: Research Funding; Sunesis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Karyopharm: Honoraria, Research Funding; BMS: Research Funding; Kiromic: Research Funding; Otsuka: Consultancy, Honoraria. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.

Management of Chronic Myeloid Leukemia in Children and Adolescents According to Local Guidelines.the Italian Experience

Management of Chronic Myeloid Leukemia in Children and Adolescents According to Local Guidelines.the Italian Experience