Improving Understanding of MDS Using an Animated Patient's Guide to Benefit Patient Health Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
David A. Sallman ◽  
Tracey Iraca ◽  
Casey L. O'Connell ◽  
Rafael Bejar ◽  
Sandra Kurtin
Keyword(s):  
Social Media ◽  
Health Outcomes ◽  
Myelodysplastic Syndromes ◽  
Research Funding ◽  
Treatment Options ◽  
Shared Decision ◽  
Advisory Committees ◽  
New Information ◽  
Patient Health ◽  
Learner Responses

Background: Patients with MDS continue to report gaps in knowledge, particularly where understanding of disease risk, prognosis and treatment options are concerned.1 A recent online social media survey on experiences in myelodysplastic syndromes revealed that patients/caregivers' (n=127) have a general lack of information about MDS and insufficient knowledge regarding treatment options and are unable to make fully informed decisions.2 Efforts to improve patient and caregiver understanding of MDS, including treatment options, are critical to individualized treatment planning and shared decision-making. MDS patients commonly use multimedia and online resources to seek disease information.3 The MDSF introduced an online 'animated,' visual format educational program in July 2018 aimed at improving patient and caregiver knowledge.4 Evaluation of this project, including determining changes in patient knowledge and intent-to-implement a change in behavior are described as parameters of advancing and benefiting health outcomes. Methods: An Animated Patient's Guide to MDS (APG), a multimedia educational initiative was launched globally in July 2018. Recruitment was conducted via search engine marketing, social media promotions and email campaigns to MDS patients, caregivers and oncology provider audiences. Video views, duration of use, and learner responses to questions on the APG website were collected from July 2018 to July 2020 (24 months). Total APG views, most frequently viewed MDS animations and MDS expert videos were monitored on the website and on You Tube, to measure learner responses to outcome-based questions, and learner intent-to-implement changes. Results: A total of 151,231 views, including 58,947 unique visitors visited the APG online resource. Of these, 81% were from the U.S. and 19% from other countries (> 50 countries). Unique visitors from U.S. consisted of 28,171 patients, 15,279 family/caregivers, and 1,910 health providers. Among responses indicating a 'commitment to change', 96% reported they will 'use new information learned to better self-manage their MDS' (n = 917), 93% reported they 'will discuss information learned with their doctor' (n = 355), and 97% reported they 'plan to discuss MDS treatment options with their doctor' (n = 734). Patients who reported they 'learned new information about MDS' identified that they 'learned new general information about MDS' (95%, n = 193), 'learned new information about the diagnosis of MDS' (86%, n = 195), 'learned about new treatment options for MDS' (89%, n = 195), 'learned about new information related to bone marrow transplant in MDS' (85%, n = 177) and intended to 'ask their doctor about how to take part in healthcare decisions' (96%, n = 187). Conclusion: Multimedia education, including visual 'animated' formats, tailored to the needs of MDS patients has the potential to provide effective learning, increase knowledge and improve engagement in shared decision-making. Ongoing monitoring and further analysis of this multimedia educational resource for MDS patients will be necessary to understand how tailored education provided via this format impacts and benefits patient health outcomes. References: 1. Kurtin, S., Chang, E., & Bently, T. (2015). MDS patient characteristics associated with use of disease-modifying therapy: results of a patient survey. The International MDS Symposia, Washington, D.C. 2. Booth, A., Bell, T., Halhol, S., Pan, S., Welch, V., Merinopoulou, E., Lambrelli, D., Cox, A. Using Social Media to Uncover Treatment Experiences and Decisions in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome Who Are Ineligible for Intensive Chemotherapy. J Med Internet Res 2019 Nov; 21(11) e-14285 3. Kurtin, S., Harrison, L., Iraca, T., Hassan, A., Nichols, A. Health Technology Engagement and Communicative Health Literacy in Older Adults MDS Patients. Myelodysplastic Syndromes, 15th International Symposia on Myelodysplastic Syndromes. Copenhagen. May 8-1, 2019. Poster presentation. 4. MDS Foundation, Inc. and Mechanisms in Medicine Inc. (2019-06-26). You And MDS: An Animated Patient's Guide to Myelodysplastic Syndromes. www.YouAndMDS.com Disclosures Sallman: Agios, Bristol Myers Squibb, Celyad Oncology, Incyte, Intellia Therapeutics, Kite Pharma, Novartis, Syndax: Consultancy; Celgene, Jazz Pharma: Research Funding. Iraca:MDS Foundation: Membership on an entity's Board of Directors or advisory committees. Bejar:Celgene/BMS: Honoraria, Research Funding; Forty-Seven/Gilead: Honoraria; Genoptix/NeoGenomics: Honoraria; AbbVie/Genentech: Honoraria; Daiichi-Sankyo: Honoraria; Aptose Biosciences: Current Employment; Takeda: Honoraria, Research Funding; Astex/Otsuka: Honoraria. Kurtin:MDS Foundation: Membership on an entity's Board of Directors or advisory committees.

Efficacy Outcomes of Treatments for Double Relapsed/Refractory Follicular Lymphoma (R/R FL): A Systematic Literature Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-43
Author(s):  
Brad S. Kahl ◽  
Anik R. Patel ◽  
Omer Zaidi ◽  
Sonya J. Snedecor ◽  
Anna G. Purdum
Keyword(s):  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Board Of Directors ◽  
Clinical Data ◽  
Research Funding ◽  
Treatment Options ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Disease Stage ◽  
Advisory Committees

ABSTRACT Introduction: Patients with indolent non-Hodgkin lymphomas (iNHL), including follicular lymphoma (FL), have high response to first-line treatment. However, retreatment is often required when relapses occur, and those with multiple relapses represent a patient population with an unmet need for effective treatment. Clinical data for several treatment options exist for the general relapsed and refractory (R/R) population; however, there are relatively fewer data specific to FL patients with ≥2 lines of prior treatment. This work systematically identified the available efficacy data in the double R/R FL population. Methods: The MEDLINE and EMBASE databases were searched through February 10, 2020. Studies were limited to interventional clinical trials of R/R FL patients (or mixed histologies with a predominance of FL) and articles published in English. Studies also must have reported one or more efficacy measures, such as overall response rate (ORR), complete response (CR), duration of response (DoR), time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). Potential interventions of interest were lenalidomide ± rituximab (R), duvelisib, ibrutinib, venetoclax, polatuzumab vedotin + R, obinutuzumab, copanlisib, umbralisib, idelalisib, and tazemetostat. Results: Of 35 publications examining treatment outcomes in R/R FL patients, only 14 (representing 5 unique clinical trials) were specific to the ≥ 2-line population. These trials were: CHRONOS Part B (copanlisib), DAWN (ibrutinib), DELTA (idelalisib), DYNAMO (duvelisib), and Morschhauser et al. 2019 (tazemetostat) and included a total of 605 participants. All studies used similar inclusion criteria, and patients included were similar in age (median 62-65), disease stage (III/IV), and ECOG score (0-2). Patients in the CHRONOS study had a median number of prior treatments of 2, whereas those in the DELTA study had 5. ORR ranged from 21% (ibrutinib) to 59% (copanlisib) (Table). The DoR ranged from 8.3 months in tazemetostat patients with EZH2 gene mutation to 19.4 months for ibrutinib. PFS ranged from 5.7 months in tazemetostat patients with wild-type EZH2 to 11.2 months for copanlisib. Median TTNT was only reported in the DAWN study (16 months). Conclusions: Very few clinical data exist reporting efficacy outcomes specific to the double R/R FL population. The limited data indicate that current treatments do not produce durable responses for most double R/R FL patients, demonstrating an unmet need. Further research is needed to fully understand the efficacy and safety of other potential interventions for this population. Disclosures Kahl: Genentech:Consultancy;Pharmacyclics LLC:Consultancy;AstraZeneca Pharmaceuticals LP:Consultancy, Membership on an entity's Board of Directors or advisory committees;ADC Therapeutics:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Celgene Corporation:Consultancy;AbbVie:Consultancy;Roche Laboratories Inc:Consultancy;BeiGene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen:Consultancy, Membership on an entity's Board of Directors or advisory committees;Acerta:Consultancy, Research Funding.Patel:Kite, a Gilead Company:Current Employment.Zaidi:BMS:Consultancy.Snedecor:Pharmerit - an OPEN Health Company:Other: Employment at consultancy paid by Kite Pharma to conduct this work.Purdum:Kite, a Gilead Company:Current Employment.

The Tolerability of Combination Therapy with Thalidomide and 5-Azacitidine in Patients with Advanced Myelodysplastic Syndromes (MDS).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1749-1749 ◽  
Author(s):  
Melita K Kenealy ◽  
John F Seymour ◽  
Cowan Linda ◽  
Alvin Milner ◽  
Pratyush Giri ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myelodysplastic Syndromes ◽  
Research Funding ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Respiratory Disorder ◽  
Advisory Committees ◽  
Impaired Performance

Abstract Abstract 1749 Poster Board I-775 Introduction Both thalidomide (Thal) and 5-azacitidine (Vidaza; AZA) have single-agent activity in patients (pts) with myelodysplastic syndromes (MDS), but there is limited experience with the combination. The addition of Thal to AZA may improve efficacy, but tolerability of the combination may be limited by side-effects. Patients and Methods This analysis included all evaluable pts on the Ph I/II Australasian Leukaemia and Lymphoma group (ALLG) MDS3 study of Thal and AZA. Pts were eligible if they had any FAB subtype of MDS; those with RA and RARS also required clinically significant cytopenias. Pts were excluded if they had previously received Thal or its derivatives or any demethylating agent. All pts were treated with Thal 50mg/d for the first 28d increasing to 100mg/d for a max of 12 Mo treatment and AZA 75mg/m2/d x7d every 28d until progression or prohibitive toxicity. The protocol specified dose delays or reductions for treatment-related toxicities. Results A total of 80 pts have been enrolled, with 41 treated between 7/08 – 7/09 currently evaluable. Median age is 68.5y (42-81) with 66% male. FAB MDS category was RA 15%, RARS 10%, RAEB 46%, RAEB-t 10% and CMML 17% with IPSS low 12%, intermed-1 37%, intermed-2 34% and high 12%. Median baseline Hb 88g/L (71-127), ANC 1.91×10 9/L (0.06-87.65) and platelets 75 ×10 9/L (10-399). Median time post diagnosis was 9 Mo. Seventeen pts (41%) remain on treatment with AZA alone (n=3) or both agents (n=14) with a median follow-up of 208d (60-297d). For those still on Thal and AZA median exposure to Thal is 209d (60-297d), with a median 7 cycles of AZA (2-9). For those 27 ceased Thal median exposure was 49d (17-220d) and of 24 ceasing AZA, median number cycles was 2 (1-8). Of 27 pts ceasing one (n=3) or both (n=24) agents; 7 withdrew consent, 3 at investigator decision, 4 for toxicity, 6 progressive disease, 1 lack of efficacy, 2 death (1 respiratory failure in setting of PD and WCC>300, 1 sepsis) and 4 unknown. There were 3 additional deaths within 28d of ceasing study therapy (all with PD); 2 due to sepsis and 1 intracranial haemorrhage. No pt experienced peripheral neuropathy Gr3 or worse. During cycle 1 of the first 40 consecutive patients on treatment, there were 18 episodes of Gr3+ non-haematologic toxicity in 13 patients; this was more likely in those with ECOG 2 (67% v 26%, p=0.053), age>65y (39% v 19%, p=0.175) and baseline ANC'0.5 (75% v 21%, p=0.008). Most of these events were infection related (a recognised risk of underlying MDS and of AZA alone); others occurred on only one occasion each (syncope, postop hemorrhage, respiratory disorder, renal failure, abdominal pain, pain, thrombosis and hypokalemia). Conclusions The combination of Thal 50-100mg/d and standard dose AZA is feasible without unexpected toxicity. Infections are common in the first cycle, particularly in pts with baseline neutropenia or impaired performance status. An updated toxicity analysis will be presented. Disclosures Kenealy: Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Seymour:Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mills:Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees. Szer:Celgene Pty Ltd: Honoraria, Speakers Bureau.

Pomalidomide Plus Low-Dose Dexamethasone In Myeloma Refractory to Both Bortezomib and Lenalidomide: Comparison of Two Dosing Strategies In Dual-Refractory Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 863-863 ◽  
Author(s):  
Martha Lacy ◽  
Sumithra Mandrekar ◽  
Morie Abraham A Gertz ◽  
Suzanne R. Hayman ◽  
Kristen Detweiler Short ◽  
...  
Keyword(s):  
Research Funding ◽  
Treatment Options ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Therapeutic Benefit ◽  
Hematologic Toxicity ◽  
Phase Ii Trials ◽  
Advisory Committees ◽  
Dosing Strategies ◽  
Grade 3

Abstract Abstract 863 Background: Patients with MM who have progressed after multiple novel agents have limited treatment options. Pomalidomide (CC4047) is the newest immunomodulatory (IMiD) agent. Pom/dex using a dose of 2 mg/day has demonstrated response rates (≥PR) of 63% in relapsed MM (Lacy, JCO 2009, 27:5008-5014) and 32% in a lenalidomide-refractory cohort (Lacy, Leukemia, in press). The maximum tolerated dose has been determined to be 4 mg/day for 21 of 28 days (Richardson, ASH, 2009), We opened two sequential phase II trials using the Pom/dex regimen at differing doses to study the efficacy of this regimen in patients who have failed both lenalidomide and bortezomib. Methods: Patients refractory to both lenalidomide and bortezomib therapy; defined as relapsing on or within 60 days of stopping each regimen, were enrolled. Pomalidomide was given orally 2 mg daily (Cohort A) or 4mg daily (Cohort B) on days 1–28 of a 28-day cycle with oral dexamethasone given 40 mg daily on days 1, 8, 15 and 22. Response was assessed by the International Myeloma Working Group Uniform Response criteria. All patients received aspirin 325 mg daily for DVT prophylaxis. Results: 35 patients with relapsed and resistant/refractory to both lenalidomide and bortezomib were enrolled in each cohort. The median age was 62 years (range, 39–77) in Cohort A and 61 (range, 45–77) years in Cohort B. The median time from diagnosis to enrollment was 57 months for Cohort A (range 12–249) and 72 months(range, 13–183) for Cohort B. 15 patients had high risk molecular markers in Cohort A and 16 in Cohort B. The median number of prior regimens was 6 in both groups. The median (range) duration on treatment was 5(1-13) and 2(0-6) cycles in cohorts A and B respectively. Toxicity at least possibly attributed to drug consisted primarily of myelosuppression: grade 3/4 neutropenia (37% Cohort A vs. 55% Cohort B); grade 3/4 thrombocytopenia (11% Cohort A vs. 13% Cohort B); and grade 3/4 anemia (9% Cohort A vs. 16% Cohort B). Grade 3/4 non-hematologic toxicities occurred in 23% Cohort A vs. 13% Cohort B. Grade 1 or 2 fatigue was the most common non-hematologic toxicity seen in 43% Cohort A vs. 52% Cohort B. Grade 1 or 2 neuropathy occurred in 17% Cohort A vs. 16% Cohort B. Other non-hematologic toxicities occurring in <5% included pneumonitis, hyperglycemia, renal failure, thrombosis. One patient in cohort B had grade 4 hepatitis. Confirmed responses in Cohort A consisted of VGPR 14%, PR 11%, and MR 24% (ORR 49%, 95% CI: 31–66), and responses in Cohort B consisted of VGPR 9%, PR 20%, and MR 12% (ORR 40%, 95% CI: 23–58). The median follow-up on alive patients was 7.5 months, and 3 months in Cohorts A and B, respectively. The median PFS in cohorts A and B are respectively 6.4 months (95% CI: 4.7-NR) and 3.3 months (95% CI: 2.3-NR). Conclusions: Pom/dex is remarkably active and well tolerated in this heavily pre-treated population of dual bortezomib/lenalidomide-refractory MM patients. The majority of patients have not progressed and objective responses (MR or better) are seen in 40–49%. This study confirms therapeutic benefit for Pom/dex in patients relapsing after other novel therapies. These studies do not show an advantage for the 4 mg/day on days 1–28 of each 28 day cycle did not show an advantage over the 2 mg/day on days 1–28 of each 28 day cycle. Disclosures: Lacy: Celgene: Research Funding. Gertz:Celgene: Honoraria; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Fonseca:Genzyme: Consultancy; Medtronic: Consultancy; BMS: Consultancy; AMGEN: Consultancy; Otsuka: Consultancy; Celegene: Consultancy, Research Funding; Intellikine: Consultancy; Cylene: Research Funding; Onyx: Research Funding; FISH probes prognostication in myeloma: Patents & Royalties. Bergsagel:Celgene: Consultancy; Centocor: Consultancy; Genentech: Consultancy; Amgen: Consultancy; Novartis: Consultancy. Stewart:Celgene: Honoraria.

scholarly journals Trial in Progress: Asciminib in Monotherapy 4 CML (AIM4CML), a Phase IIIb Study of Asciminib Monotherapy in Patients with Chronic Myeloid Leukemia in Chronic Phase without or with T315I Mutations

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3599-3599
Author(s):  
David Andorsky ◽  
Sarah Tomassetti ◽  
Yehuda E. Deutsch ◽  
E Randolph Broun ◽  
Ghayas C. Issa ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Kinase Activity ◽  
Treatment Options ◽  
Chronic Phase ◽  
Advisory Committees ◽  
Phase Iiib ◽  
T315i Mutation ◽  
Previously Treated

Abstract BACKGROUND: Chronic myeloid leukemia (CML) is driven by the constitutively active BCR-ABL1 tyrosine kinase. Several adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) are approved that inhibit BCR-ABL1 activity, and these have transformed CML from a fatal disease to a chronic one with near-normal life expectancy. However, many patients (pts) experience resistance to or intolerance of successive lines of TKI therapy. These pts have poor outcomes and few remaining treatment options. Moreover, pts with CML harboring the T315I mutation have limited treatment options as they are resistant to all approved TKIs except for ponatinib. Hence, there is a need for new CML therapies that are effective and well tolerated. Asciminib is an investigational agent with a novel mechanism of action. It is the first BCR-ABL1 inhibitor that inhibits BCR-ABL1 kinase activity by Specifically Targeting the ABL Myristoyl Pocket (STAMP). This contrasts with approved TKIs that target the ATP site of BCR-ABL1 to inhibit its kinase activity but are not entirely BCR-ABL1-specific and may target other kinases. In the phase III ASCEMBL trial in pts with CML in chronic phase (CP) after prior treatment with ≥2 ATP-competitive TKIs, asciminib showed superior efficacy vs bosutinib: major molecular response (MMR; BCR-ABL1 on the International Scale ≤0.1%) rate at week 24 was 25.5% vs 13.2%, respectively. In a large phase I trial, asciminib demonstrated promising efficacy and safety in pts with CML-CP without the T315I mutation previously treated with ≥2 TKIs and in those with the T315I mutation previously treated with ≥1 TKI: by 6 months, 37% and 25% of pts, respectively, achieved or maintained an MMR. Here, we describe the AIM4CML trial that was initiated to further assess the efficacy and safety of asciminib and explore a once-daily (QD) dosing regimen in pts with CML-CP (ClinicalTrials.gov, NCT04666259). DESIGN: This is a multicenter, phase IIIb, open-label, 3-cohort study of asciminib in pts with CML-CP without T315I after ≥2 prior TKIs and pts with T315I after ≥1 prior TKI (Figure 1). Adults aged ≥18 years with a diagnosis of CML-CP are eligible. Pts must have treatment failure with (as per 2020 European LeukemiaNet recommendations) or intolerance of the most recent TKI at screening. Key eligibility criteria are described in Table 1. Pts without the T315I mutation will undergo random selection to receive either asciminib 40 mg twice daily (BID; cohort A) or 80 mg QD (cohort B); those with the T315I mutation will receive asciminib 200 mg BID (cohort C). OBJECTIVES AND ENDPOINTS: The primary objective is to evaluate the safety profile of asciminib 40 mg BID and 80 mg QD in pts with CML-CP without T315I after ≥2 prior TKIs and of asciminib 200 mg BID in pts with T315I after ≥1 prior TKI. Primary endpoint analyses include incidence and severity of adverse events (AEs), serious AEs, changes in laboratory values and vital signs, and incidence of notable electrocardiogram abnormalities for 24 weeks. Primary and secondary study objectives/endpoints are summarized in Table 2. CONCLUSIONS: The AIM4CML study is currently enrolling pts across multiple sites in the United States, with an anticipated enrollment of approximately 115 heavily pretreated pts with CML-CP. Asciminib has the potential to transform the standard of care in this pt population through its novel mechanism of action as a BCR-ABL1 inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP). This study is sponsored by Novartis. Figure 1 Figure 1. Disclosures Andorsky: AbbVie: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; AbbVie: Research Funding; AstraZeneca: Other: served on steering committees; Celgene/Bristol Myers Squibb: Research Funding; Epizyme: Research Funding. Tomassetti: Seagene: Research Funding; Rigel: Research Funding; Beigene: Research Funding; Natera: Research Funding; Novartis: Research Funding; Parexel: Research Funding. Deutsch: Astellas: Membership on an entity's Board of Directors or advisory committees. Issa: Syndax Pharmaceuticals: Research Funding; Novartis: Consultancy, Research Funding; Kura Oncology: Consultancy, Research Funding. Levy: Dova: Consultancy, Other: Promotional speaker; Gilead Sciences, Inc.: Consultancy, Honoraria, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Novartis: Consultancy, Other: Promotional speaker; Epizyme: Consultancy, Other: Promotional speaker; AbbVie: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Beigene: Consultancy, Honoraria, Speakers Bureau; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Other: Promotional speaker; Amgen Inc.: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Morphosys: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau. Deininger: Sangamo: Consultancy, Membership on an entity's Board of Directors or advisory committees; SPARC, DisperSol, Leukemia & Lymphoma Society: Research Funding; Blueprint Medicines Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Part of a Study Management Committee, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Part of a Study Management Committee, Research Funding; Fusion Pharma, Medscape, DisperSol: Consultancy. Maegawa: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Shrestha: Novartis: Current Employment. Mauro: Bristol Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Sun Pharma / SPARC: Research Funding.

scholarly journals Treatment Decision Making and Treatment Satisfaction Among Individuals Living with Chronic Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4787-4787
Author(s):  
Julie Olson ◽  
Shauna McManus ◽  
Melissa F. Miller ◽  
Thomas W. LeBlanc ◽  
Eva Yuen ◽  
...  
Keyword(s):  
Decision Making ◽  
Treatment Outcomes ◽  
Board Of Directors ◽  
Research Funding ◽  
Treatment Options ◽  
Treatment Decision ◽  
Treatment Decisions ◽  
Advisory Committees ◽  
Treatment Decision Making ◽  
Satisfaction With Treatment

Abstract Background: Over the past decade, an increase in treatment options for chronic myeloid leukemia (CML) has dramatically changed the therapeutic landscape and has improved clinical outcomes. This abundance of treatment options may make it difficult for CML patients to feel knowledgeable about what options are available to them, may hinder patients' preparedness for having conversations about treatment, and, similarly, may contribute to patients feeling less involved in treatment decision making (TDM). In light of this changing landscape, we explored whether the TDM experience was linked to satisfaction with treatment outcomes in a national sample of CML patients. Methods: Using data from the Cancer Support Community's Cancer Experience Registry®, our analytic sample included 310 participants who reported CML as their primary diagnosis. The dependent variable in all analyses was a dichotomous, patient-reported indicator of satisfaction with treatment outcomes (satisfied or not satisfied). Our independent variables include three measures that capture the TDM experience: feeling involved in the TDM process; feeling knowledgeable about treatment options prior to making treatment decisions; and, feeling prepared to discuss treatment options with one's doctor. Respondents ranked TDM knowledge, preparedness, and involvement from 0 = "not at all" to 4 = "very much." Responses were dichotomized such that 1 = "quite a bit" or "very much" and 0 = "not at all," "a little bit" or "somewhat." Analytically, we compared patients who reported high satisfaction with treatment outcomes to those who reported low satisfaction, using Student's t-test. Then, we estimated multivariate logistic regression models predicting odds of being satisfied with treatment outcome by TDM knowledge, preparedness, and involvement. Regression models controlled for demographic characteristics including age, gender, and race; clinical factors such as time since diagnosis and symptom burden; treatment-related measures including financial impact of treatment; and the degree to which individuals felt their health care teams prepared them to manage treatment side effects. Results: Descriptively, our sample was 65% female and 87% non-Hispanic White, with an average age of 56.6 years (SD = 12) and mean time since diagnosis of 6 years (SD = 5). Most (74%) reported being "quite a bit" to "very much satisfied" with their treatment outcomes. Experiences with TDM, however, were variable. When making treatment decisions, 52% reported feeling involved, 41% reported feeling knowledgeable, and 21% felt prepared. Importantly, t-test results suggested that individuals with greater involvement, more knowledge, and higher preparedness were significantly more likely to report satisfaction with treatment outcomes. Results of the multivariate models demonstrated a greater likelihood of treatment satisfaction among individuals who felt prepared to discuss treatment options with their health care team, even after controlling for demographic, clinical, and treatment-related characteristics. In fact, prepared individuals were nearly 6 times as likely to be satisfied with their treatment outcomes, as compared to individuals who did not feel prepared to discuss treatment options (p < .05). Conclusion: Most of our patients with CML did not feel prepared to make treatment decisions. However, those who feel more prepared to discuss treatment options with their doctors are also more likely to report satisfaction with treatment outcomes. As new CML treatment options become available, our results highlight the need for an increased focus on shared decision making in clinical practice. This may necessitate providing patients with more resources to help prepare them for treatment-related conversations. Disclosures Birhiray: Takeda: Research Funding, Speakers Bureau; Genomic Health: Patents & Royalties; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion: Consultancy; Puma: Research Funding, Speakers Bureau; Pharmacyclics: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Norvatis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Eli-Lilly: Speakers Bureau; Excelis: Speakers Bureau; Clovis Oncology: Speakers Bureau; Sanofi Oncology: Speakers Bureau; Incyte: Speakers Bureau; AstraZeneca: Speakers Bureau; Tessaro: Speakers Bureau; Pfizer: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Helsinn: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Maintenance with Weekly Carfilzomib in Elderly Newly Diagnosed Multiple Myeloma (IFM 2012-03)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3190-3190
Author(s):  
Arthur Bobin ◽  
Guillemette Fouquet ◽  
Alain Duhamel ◽  
Salomon Manier ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Rate ◽  
Treatment Options ◽  
Maintenance Phase ◽  
Prolonged Survival ◽  
Second Phase ◽  
Advisory Committees ◽  
Additional Information

Background. Continuous therapy, such as maintenance approach, appears to be a major therapeutic change in multiple myeloma, improving response rate and overall survival. Novel agents widen the range of treatment options, still Lenalidomide (IMiD) is widely used in this indication. Even though usually well tolerated, it remains a daily treatment, and can lead to some side effects on a long term basis. Carfilzomib, a second generation PI, allows interesting response rate and prolonged survival, with manageable adverse events. Nevertheless, only few clinical trials focused on its use in maintenance rather than in first or second line treatment. We therefore thought to study the role of 1 year Carfilzomib exposure following KMP IFM 2012-03. Methods. IFM 2012-03 is a multicenter phase I study for eNDMM (patients aged 65 years old and more) that determined the maximal tolerated dose of weekly carfilzomib, associated with melphalan and prednisone (KMP), at 70mg/m². The following results will concern the second phase of the study using intravenous Carfilzomib monotherapy in maintenance. K was administered at 36 mg/m² for 13 cycles on an every 2 weeks schedule. Results. Thirty eNDMM were recruited in IFM 2012-03. Median age is 75, with 56% R-ISS 2 or 3 and 11% high-risk cytogenetic. With K weekly from 36 to 70mg/m², ORR is reported at 93.3%, including 46.7% ≥CR ; median PFS is 35.8 months and median OS was not reached. Twenty-two (73%) patients started K maintenance and 16 (73%) completed it. Four patients progressed and 2 stopped for AEs (renal amylosis, sensory neuropahty) during the maintenance phase. At maintenance completion, 50% were ≥CR. From the start of maintenance, in landmark analysis, median PFS is 28.1 months and the estimated 36-months OS approximately 70%. Moreover, 3 patients (14%) improved their responses during maintenance. Conclusion. Carfilzomib monotherapy can be used safely in maintenance for 1 year in eNDMM, including for patients above 75 years. K maintenance may lead to deep response rate, certainly a most relevant prognostic factor for prolonged survival. Therefore, Carfilzomib maintenance, characterized with a simple administration modality, might be considered as an alternative to Lenalidomide and integrate the armamentarium of prolonged therapy in eNDMM. Further studies should still bring additional information in order to confirm our results. Disclosures Karlin: AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kolb:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: travel and registration for my participation to international medical congres (ASH). Jaccard:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria; Abbvie: Honoraria. Belhadj:Celgene: Other: personal fees from Celgene, personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, outside the submitted work. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Hulin:Janssen, AbbVie, Celgene, Amgen: Honoraria; celgene: Consultancy, Honoraria. Leleu:Karyopharm: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Oncopeptide: Honoraria.

scholarly journals Imerge: A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) That Is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4248-4248 ◽  
Author(s):  
Uwe Platzbecker ◽  
David P. Steensma ◽  
Koen Van Eygen ◽  
Azra Raza ◽  
Valeria Santini ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myelodysplastic Syndromes ◽  
Research Funding ◽  
Phase 2 ◽  
Employment Equity ◽  
Phase 3 ◽  
Advisory Committees ◽  
Equity Ownership ◽  
The Impact ◽  
Rbc Transfusion

Background: Current treatment options for red blood cell (RBC) transfusion-dependent (TD) patients with lower risk (LR) myelodysplastic syndromes (MDS) relapsed after or refractory to erythropoiesis-stimulating agents (ESAs) have limited efficacy and durability; new approaches are needed. Imetelstat is a 13-mer lipid-conjugated oligonucleotide that targets the RNA template of human telomerase and is a competitive inhibitor of telomerase enzymatic activity (Asai et al, Cancer Res 2003; Herbert et al, Oncogene 2005). Preclinical, in vivo xenograft models (Dikmen et al, Cancer Res 2005; Hochreiter et al, Clin Cancer Res 2006) and preliminary clinical data from a pilot study conducted at Mayo Clinic (Tefferi et al, Blood Cancer Journal 2016) supported initiation of a study in TD LR MDS patients. A Phase 2 study of imetelstat, IMerge, demonstrated an 8-week RBC transfusion independence (RBC-TI) rate of 42%, 24-week RBC-TI rate of 29%, and 68% erythroid hematologic improvement (HI-E) rate in 38 heavily TD patients (median prior RBC transfusion burden 8 units / 8 weeks over the 16 weeks pre-study period) with LR MDS. Responses were durable with median duration of 8-week RBC-TI of 85.9 weeks by Kaplan Meier estimates (range 8.0-140.9) (Steensma ASH 2018, Fenaux EHA 2019). These Phase 2 results provided further evidence of potential clinical benefit of imetelstat treatment in TD LR MDS, and supported initiation of a Phase 3 trial. Methods: IMerge is two-part, Phase 2/3 study (ClinicalTrials.gov: NCT02598661). The Phase 2 portion of the study described above is closed for enrollment. The Phase 3 portion of the study is open for enrollment of adult patients with International Prognostic Scoring System (IPSS) low or intermediate-1 risk, non-del(5q) MDS, who are TD, are relapsed after or refractory to ESAs, and have not received treatment with lenalidomide or hypomethylating agents. The study is a randomized (2:1) double-blind, placebo-controlled trial to compare efficacy of imetelstat vs. placebo that will enroll approximately 170 patients and will be conducted at approximately 90 centers in North America, Europe, Asia and Middle East. Imetelstat will be administered as 2-hour IV infusion every 4 weeks at 7.5 mg/kg. The primary endpoint of the study is to assess the rate of RBC-TI lasting ≥8 weeks. Secondary endpoints include safety, rate of RBC-TI ≥24 weeks, time to RBC-TI start, RBC-TI duration, rate of HI-E, the amount and relative change in RBC transfusions, rate of CR or PR, overall survival, progression of MDS, pharmacokinetics and effect of treatment on quality of life. Biomarkers relevant to the mechanism of action of imetelstat will be assessed to demonstrate target inhibition and their association with clinical responses. Cytogenetics and mutation analyses will be performed to evaluate the impact of imetelstat on reduction/depletion of malignant clones leading to disease modification. Disclosures Platzbecker: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria. Steensma:Astex: Consultancy; Arrowhead: Equity Ownership; Summer Road: Consultancy; Onconova: Consultancy; Aprea: Research Funding; Pfizer: Consultancy; Stemline: Consultancy; H3 Biosciences: Other: Research funding to institution, not investigator.. Santini:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria; Acceleron: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees. Germing:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Amgen: Honoraria. Font:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees. Díez-Campelo:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Patnaik:Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Sherman:Geron Corporation: Employment, Equity Ownership. Dougherty:Geron Corporation: Employment, Equity Ownership. Feller:Geron Corporation: Employment. Sun:Geron Corporation: Employment, Equity Ownership. Wan:Geron Corporation: Employment, Equity Ownership. Huang:Geron Corporation: Employment, Equity Ownership. Rizo:Geron Corporation: Employment, Equity Ownership. Fenaux:Celgene Corporation: Honoraria, Research Funding; Aprea: Research Funding; Astex: Honoraria, Research Funding; Jazz: Honoraria, Research Funding.

Validation of a Flow Cytometric Scoring System for the Prognostication of the Myelodysplastic Syndromes: a Retrospective Cohort Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4012-4012
Author(s):  
Canan Alhan ◽  
Theresia M. Westers ◽  
Claudia Cali ◽  
Gert J. Ossenkoppele ◽  
Arjan A. Van de Loosdrecht
Keyword(s):  
Healthy Volunteers ◽  
Board Of Directors ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Research Funding ◽  
Classification Systems ◽  
Prognostic Information ◽  
Advisory Committees ◽  
Flow Cytometric ◽  
Myeloid Progenitors

Abstract Abstract 4012 The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders, characterized by cytopenia(s), dysplasia and a propensity to evolve into acute myeloid leukemia. The International Prognostic Scoring System (IPSS) and WHO-based prognostic scoring system provide prognostic information. However, even if patients are allocated in the same risk category their clinical course remains heterogeneous. Recent developments in the treatment of MDS require refinement of prognostication and identification of patients who might benefit from treatment with potentially disease modifying agents such as lenalidomide or azacitidine. Flow cytometry (FC) is emerging as a valuable technique for the diagnosis and prognosis of MDS. Recently, we demonstrated that flow cytometric analysis of BM in low and int-1 risk MDS is instrumental to identify clinically relevant subgroups. (Westers et al, Blood 2010) Previously, it was reported that a flow cytometric scoring system (FCSS) is predictive for worse outcome in MDS. (Wells et al, Blood 2003, van de Loosdrecht et al, Blood 2008) The FCSS is a scoring system that allows for a numerical display of immunophenotypic aberrancies in the (im)mature myelo-monocytic lineage. Scores are generated by enumerating abnormalities; a high score reflects a high number of aberrancies. The current study aimed to validate the FCSS for identification of prognostic subgroups in MDS. We analyzed aberrancies in (im)mature myelo-monocytic cells by FC in BM of 102 MDS patients, including 48 MDS patients from the previous cohort. The diagnoses according to WHO 2001 classification were RA(RS) n=19, RCMD(RS) n=54, RAEB-1 n=11, RAEB-2 n=13, MDS-U n=5 and also age-matched healthy volunteers (n=39) were included. The median age of MDS patients was 66 and of healthy volunteers 57. The FCSS in RA(RS) (median=3, range 1–6) patients was significantly higher compared with healthy controls (median=1, range 0–2, p<0.001). In contrast to our previous results the FCSS for RA(RS) and RCMD(RS) patients did not differ. This is a remarkable finding, since by morphology RA(RS) patients have unilineage dysplasia, in contrast to flow cytometric findings, where 84% (16/19) of the RA(RS) patients had two or more aberrancies in the (im)mature myelomonocytic compartment. The FCSS was higher in RAEB-1 (median=6, range 2–7) and RAEB-2 (median=6, range 4–8) compared with RCMD(RS) (median=3, range 0–6, p=0.02 and p<0.0001, respectively). Overall, the FCSS correlated significantly with WHO 2001 classification (p<0.0001). The FCSS showed a significant correlation with IPSS categories low, int-1, int-2 and high (p<0.0001). Remarkably, the FCSS was not correlated with cytogenetic risk categories low, intermediate and poor. The new German-Austrian Cytogenetic Prognostic Scoring System for MDS was also not correlated with the FCSS. This indicates that the FCSS and cytogenetics might provide separate prognostic information in MDS. Neutrophil granularity corresponding with side scatter by FC was significantly decreased in MDS patients compared with healthy volunteers (p<0.0001). In the RA(RS) and RCMD(RS) category, 40% (29/73) of patients expressed an aberrant marker such as CD5, CD7 and/or CD56 on myeloid progenitors. Transfusion data was available of 51 patients. Interestingly, the majority of MDS patients who were transfusion dependent or progressive, had aberrant expression of CD5, CD7 and/or CD56 on myeloid progenitors compared with MDS patients without aberrant marker expression (64% (16/25) vs 31% (8/26), respectively p=0.04). When the cumulative amount of all aberrancies in the (im)mature myelo-moncytic cells were taken into account, transfusion dependent patients had significantly more aberrancies than transfusion independent MDS patients, (median 6.5 vs 4, respectively, p=0.006). In conclusion, we here confirmed our previous findings in a larger cohort. The majority of RA(RS) patients already has multilineage dysplasia as detected by FC, which might be of prognostic relevance. Although the FCSS correlates with current prognostic systems, a striking heterogeneity remains within prognostic subgroups. Therefore, the FCSS and detection of aberrant myeloid progenitors can provide refined prognostication by identification of patients at risk for transfusion dependency and adverse clinical outcome, independent of current classification systems. Disclosures: Ossenkoppele: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Van de Loosdrecht:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Impact of Hypomethylating Agent Therapy in Myelodysplastic Syndromes with Chromosome 3 Abnormalities

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1705-1705
Author(s):  
David Sallman ◽  
Guillermo Garcia-Manero ◽  
Elias Jabbour ◽  
Mikkael A. Sekeres ◽  
Amy E. DeZern ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Board Of Directors ◽  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Research Funding ◽  
Chromosome 3 ◽  
Advisory Committees ◽  
Monosomy 3 ◽  
Risk Patients

Abstract Background In myelodysplastic syndromes (MDS), abnormalities of chromosome 3 (i.e. inversion 3 (inv(3)), translocation 3q (t(3q)), or deletion 3q (del(3q)) represent a poor-risk karyotype in the Revised International Prognostic Scoring System (IPSS-R). In acute myeloid leukemia (AML) patients with 3q abnormalities, patients with inv(3)/t3;3 represented the most unfavorable group with a median overall survival (OS) of 10.3 months (Lugthart et al., 2010). We previously presented a single institution experience regarding outcomes of MDS patients with chromosome 3 abnormalities. Here, we sought to further define outcomes of chromosome 3 abnormalities in MDS and address the impact of hypomethylating agents (HMA) on outcome in multiple institutions. Patients and Methods Patients were identified through the MDS Clinical Research Consortium and were included if they had a WHO diagnosis of MDS, MDS/myeloproliferative neoplasm (MPN), therapy related MDS (t-MDS), or AML (20-30% myeloblasts) and had any karyotypic abnormality involving chromosome 3. Data analyzed included baseline demographics, disease characteristics, IPSS/IPSS-R scores, treatment and outcome. Responses to HMA therapy were evaluated using International Working Group (IWG) 2006 criteria. Kaplan-Meier estimates were used for overall survival. Results A total of 413 patients were identified with a median age at diagnosis of 67 years. WHO classification was as follows: 9% RA/RARS, 12% RCMD, 26% RAEB-1, 31% RAEB-2, 2% MDS/MPN, 7% MDS Unclassified, 13% AML; 34% had t-MDS. Overall, 97% of patients were higher risk by IPSS-R (i.e., intermediate to very high risk) with a median blast % in bone marrow of 8%. Distribution of cytogenetic abnormalities were inv(3) (10%), del(3q) (12%), t(3q) (18%), monosomy 3 (22%), 3p abnormalities (22%), and other chromosome 3 changes (17%). Median OS for the cohort was 12.0 months (95% C.I. 10.8 to 13.9 months) and 31% of patients without AML transformed to AML. IPSS-R was predictive of median OS across subgroups (P < 0.00001). The specific cytogenetic abnormality was predictive for survival (P < 0.00001) with median OS for t(3q) 19 months, inv(3) 13 months, del(3q) 13 months, 3p 10 months, monosomy 3 9 months, and other 3 abnormalities 11 months. There was no survival difference between patients with translocations of 3q21 versus 3q26 (median OS 18 months versus 18.6 months, P = 0.96). Patients with an isolated chromosome 3 abnormality had significantly improved OS (25.1 months versus 10.9 months (P < 0.00001). Complex karyotype (>/= 3 abnormalities) was observed in 74% of patients and was associated with decreased OS (11 months versus 21 months, P < 0.00001). Of patients who received HMA therapy (48%), the overall response rate was 46% (17% hematological improvement (HI), 7% PR, 20% CR, 2% marrow CR (CRm) with stable disease in 23%). Median OS with and without HMA was 15.5 months versus 8.4 months (p=0.038). In int-2/high risk patients by IPSS, HMA treated patient had a median OS of 14.0 months versus 7.6 months for patients not treated with HMAs (P = 0.005) with no benefit for HMAs in lower-risk patients (median OS 24.5 months with HMA versus 38.7 months without; P =0.41). Cox regression modeling with HMA therapy, IPSS and clinical site confirmed the HMA OS benefit in higher-risk patients (HR 0.69; 95% CI 0.53-0.89; P = 0.005), but showed decreased OS in lower-risk patients (HR 2.0; 95% CI 1.03-3.92; P = 0.04). Allogeneic transplantation was performed in 18% (n=75) of patients, with median OS of 18 months versus 10 months in non-transplanted patients (P < 0.00001). Conclusion In this large cohort of patients with MDS and oligoblastic AML associated with chromosome 3 abnormalities, survival was heterogeneous but overall poor, with isolated chromosome 3 abnormality and t(3q) patients having a more favorable OS than patients with other chromosome 3 anomalies. MDS patients with 3p changes have poor outcomes. Although some patients with chromosome 3 respond to HMA therapy, the overall survival remains poor and novel approaches are needed. Disclosures Sekeres: Amgen: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Steensma:Amgen: Consultancy; Celgene: Consultancy; Incyte: Consultancy; Onconova: Consultancy. Lancet:Boehringer-Ingelheim: Consultancy; Kalo-Bios: Consultancy; Pfizer: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy. List:Celgene Corporation: Honoraria, Research Funding. Komrokji:Incyte: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Research Funding, Speakers Bureau; Pharmacylics: Speakers Bureau.

Gemtuzumab in Children with Relapsed and Refractory Acute Myeloid Leukemia Treated on Compassionate-Use Basis: A Report of the AML-BFM Study Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1637-1637 ◽  
Author(s):  
Mareike Rasche ◽  
Beate Lerius ◽  
Ursula Creutzig ◽  
Martin Zimmermann ◽  
C. Michel Zwaan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Treatment Options ◽  
Refractory Disease ◽  
Compassionate Use ◽  
Advisory Committees ◽  
Acute Myeloid ◽  
Refractory Aml

Abstract BACKGROUND: Long-term survival in pediatric acute myeloid leukemia (AML) improved remarkably during the last decades. However, children with refractory disease or relapsed AML still suffer from exceedingly poor outcome, especially those who relapse within one year of diagnosis with very limited treatment options. Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody linked to calicheamicin, a potent cytotoxic agent. Developed for targeted treatment of CD33-positive AML, studies in adults showed its efficacy in relapsed and refractory AML. We performed this retrospective analysis of patients with highly advanced pediatric AML, receiving GO as compassionate use. PATIENTS AND METHOD: In total, 96 children <18 years diagnosed from 1995 to 2014 with multiple relapsed or refractory AML received GO as compassionate use. Eighty-eight patients had sufficient data available for this retrospective analysis, evaluation of adverse effects during first cycle of GO was based on medical reports of 83 patients. Sixty-one patients were treated in refractory disease or early first relapse, but also including 7 patients with 2 relapses within the first year after diagnosis. Nine patients were in 2nd relapse (>1year from diagnosis) and one patient in 3rdrelapse, four children had AML as secondary malignancy. Fourteen children have been already transplanted once, one child twice before GO therapy. Fourty-seven children received monotherapy with GO, 35 children were treated combined with cytarabine and 3 children received other combinations with other agents (3 unknown). Fifty-three patients received one cycle, 34 received 2 cycles of GO, however one patient received 4 cycles of monotherapy. Of note, eight patients have been previously reported elsewhere (Zwaan et al., Br J Haematol. 2010). Time of database lock was 07/2016 with a median follow-up of 9.8 years for the surviving patients. RESULTS: Safety profile was comparable to other pediatric studies. Adverse effects during first cycle of treatment consisted mostly of fever in neutropenia (n=49), less frequently infections (n=9) or allergic reactions (n=18). A few patients reported about mild gastrointestinal symptoms, which was not clearly related to GO due to combination therapy. Two patients suffered from sepsis. Veno-occlusive disease (VOD) of the liver occurred in three patients, one of those had a previous VOD, but all of them have been treated successfully with defibrotide. No lethal event was observed during treatment with GO. One patient developed a VOD during subsequent transplantation despite of prophylactic use of defibrotide. Sixty patients were evaluable for response assessment of the bone marrow. Twenty-eight children showed a response with a blast reduction to 5% or less in the bone marrow samples after treatment (46%). Fourteen out of these patients, received GO combined with cytarabine, 12 patients had monotherapy, and two other combinations. Subsequently, 53 children proceeded to stem cell transplantation (SCT) (one patient unknown). Of note, 13 out of those, received further chemotherapy before HSCT was performed. In details, 47 patients proceeded to first SCT, whereas 5 patients received 2ndSCT (one unknown). Time to transplantation varied (<3 weeks, n=14; 3 to 6 weeks, n=28; >6 weeks, n=11 patients [median time to transplantation after GO: 30 days]). The probability of 4-year overall survival after treatment with GO of all patients (n=88) was 21±4%. In patients treated with monotherapy it was 18±6%. Eighteen patients of this cohort are still alive at time of database lock. CONCLUSION: To our knowledge, this analysis is the largest pediatric cohort of patients, treated with GO in a very advanced disease. The results of this retrospective trial indicate efficacy of GO, while having an acceptable toxicity profile, even in heavily pretreated patients. It can induce blast reduction and even survival in patients, who have no further conventional treatment options. Further randomized studies are necessary to learn more about efficacy and side effects in a relapse setting, especially for therapeutic implications in future. Disclosures Rasche: Jazz Pharma: Other: Travel accomodation. Zwaan:Pfizer: Research Funding; Pfizer: Consultancy. Reinhardt:Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Jazz Pharma: Other: Travel Accomodation.

Sign in / Sign up

Export Citation Format

Share Document