P-182: Comparison of lenalidomide, bortezomib, dexamethasone vs bortezomib, cyclophosphamide, dexamethasone as an induction regimen in newly diagnosed myeloma patients eligible for intensive chemotherapy

2021 ◽  
Vol 21 ◽  
pp. S137
Author(s):  
Zoe Van de Wyngaert ◽  
Florent Malard ◽  
Zora Marjanovitch ◽  
Tamim Alsuliman ◽  
Souhila Ikhlef ◽  
...  
Keyword(s):  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Induction Regimen

scholarly journals Epigenetic Priming Using Decitabine Followed By Cytarabine As an Induction Regimen in Older Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2265-2265
Author(s):  
Annie Im ◽  
Jing-Zhou Hou ◽  
Anastasios Raptis ◽  
Mounzer Agha ◽  
Rafic Farah ◽  
...  
Keyword(s):  
Older Adults ◽  
Phase Ii ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Phase Ii Study ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Induction Regimen ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Background: Acute myeloid leukemia (AML) in older patients is associated with a poor prognosis, with lower complete remission (CR) rates and worse overall survival compared to younger patients. Moreover, most older patients over the age of 70 years do not tolerate standard induction chemotherapy. Alternative therapy with hypomethylating agents can improve CR rates and survival compared to best supportive care, but overall outcomes remain poor after current therapeutic options in this patient population. Preclinical studies suggest that “epigenetic priming” using decitabine followed by cytarabine increases the cytotoxicity of cytarabine. It is hypothesized that this is due to the reactivation of genes that have been silenced by the malignancy. The aim of this phase II study is to evaluate the efficacy and safety of a novel induction regimen using decitabine followed by cytarabine in older patients with newly diagnosed AML who are not candidates for intensive chemotherapy. Here we present response rates and treatment-related mortality for the first 23 evaluable subjects. Methods: A phase II, single arm study of decitabine and cytarabine is ongoing at the University of Pittsburgh Cancer Institute (NCT 01829503) for patients over the age of 70 years with newly diagnosed AML, or patients over the age of 60 years who are considered not to be candidates for intensive chemotherapy. The induction regimen consists of decitabine 20mg/m² intravenously (IV) x 5 days followed by standard dose cytarabine 100mg/m² continuous IV infusion x 5 days. Patients with no evidence of disease on day 15 bone marrow biopsy proceed with maintenance decitabine. Patients with persistent disease but no evidence of progression proceed with a second cycle of induction using the same regimen. Patients with progressive disease after 1 cycle are taken off study. After a second induction cycle, patients with no evidence of disease, or persistent disease but no evidence of progression, proceed with maintenance decitabine. Maintenance cycles consist of decitabine 20mg/m² IV x 5 days every 4-8 weeks until disease progression. Response rates are evaluated by the International Working Group Response Criteria in AML. Treatment-related mortality is defined at mortality within 8 weeks of initiation of induction therapy. Results: Twenty-five subjects of a planned 37 subjects have been enrolled as of August 2014, 23 of whom were evaluable for response at the time of analysis. At the time of this preliminary analysis, the median age was 76 years (range 68-82 years). There are 11 females (44%) and 14 males (56%). The median ECOG performance status was 1 (range 0-2). There were 14 patients with poor risk cytogenetics at diagnosis. Of the 23 patients who are evaluable for response, there were 14 (61%) patients with a CR and 2 patients with a CRi (CR+CRi rate 70%). Two patients had a partial remission, 1 patient had a morphologic leukemia free state, and 4 patients had resistant disease. All patients except for 2 received 2 cycles of induction. Of the 14 patients who had poor risk cytogenetics at diagnosis, 10 (71%) had a CR, and 8 had normalization of their previous cytogenetic abnormalities. There have been no treatment-related mortalities to date. Conclusion: We have shown that an induction regimen using decitabine as an epigenetic primer followed by cytarabine induces high CR+CRi rates with no treatment-related mortality in older adults with newly diagnosed AML who are not candidates for intensive chemotherapy, a patient population in whom there exists a dire need for novel treatment strategies. In the first report of this phase II study, 70% of patients achieved a CR or CRi, and there were no treatment related mortalities. This compares favorably with historical outcomes of both intensive chemotherapy and decitabine monotherapy in older adults in terms of safety and efficacy, respectively. Final analysis of this clinical trial will include overall survival analysis, rate of grade III and IV adverse events, and epigenetic correlative studies. We have demonstrated that decitabine followed by cytarabine is a safe and effective regimen in older adults with newly diagnosed AML. Disclosures No relevant conflicts of interest to declare.

Phase 2 Study of Epigenetic Priming Using Decitabine Followed By Cytarabine As an Induction Regimen in Older Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3739-3739 ◽  
Author(s):  
Annie Im ◽  
Mounzer Agha ◽  
Anastasios Raptis ◽  
Jing-Zhou Hou ◽  
Rafic Farah ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Older Patients ◽  
Response Rates ◽  
Intensive Chemotherapy ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Phase 2 Study ◽  
Induction Regimen ◽  
Related Mortality

Abstract Background Acute myeloid leukemia (AML) in older patients is associated with a poor prognosis, with lower complete remission (CR) rates and worse overall survival compared to younger patients. Moreover, most patients over the age of 70 years do not tolerate standard induction chemotherapy. Alternative therapy with hypomethylating agents can improve CR rates and survival compared to best supportive care, but overall outcomes remain poor with current therapeutic options. Preclinical studies suggest that "epigenetic priming" using decitabine followed by cytarabine increases the cytotoxicity of cytarabine. It is hypothesized that this is due to the reactivation of genes that have been silenced by the malignancy. The aim of this study is to evaluate the efficacy and safety of a novel induction regimen using decitabine followed by cytarabine in older patients with newly diagnosed AML who are not candidates for intensive chemotherapy. Interim response rates were reported at the ASH Annual Meeting in 2014. Here we present updated response rates, treatment-related mortality, and overall survival. Methods This is a phase 2, single arm study at the University of Pittsburgh Cancer Institute (NCT01829503) for patients over the age of 70 years with newly diagnosed AML, or patients over the age of 60 years who are considered not to be candidates for intensive chemotherapy. The induction regimen consisted of decitabine 20mg/m² intravenously (IV) x 5 days followed by cytarabine 100mg/m² continuous IV infusion x 5 days. Patients with no evidence of disease on day 15 bone marrow biopsy proceeded with maintenance decitabine after count recovery; patients otherwise proceeded with a second cycle of induction using the same regimen. Patients with progressive disease after 1 cycle were taken off study. After a second induction cycle, patients who achieved a complete or partial remission proceeded with maintenance decitabine. Maintenance cycles consisted of decitabine 20mg/m² IV x 5 days every 4-8 weeks until disease progression or toxicity. Response rates were determined by the International Working Group Response Criteria in AML. Four-week and 8-week mortality rates were assessed. Results Forty-six subjects were enrolled as of August 2015, 36 of whom were evaluable for response at the time of analysis. Median age was 76 years (range 67-88 years). There were 21 females (45%) and 26 males (55%). The median ECOG performance status was 1. There were 21 patients with poor risk cytogenetics at diagnosis. Of 36 patients who were evaluable for response, 20 patients had a CR and 5 patients had a CRi (CR/CRi rate 69%). Six patients had a partial remission, and 5 patients had resistant disease. All evaluable patients except for 6 received 2 cycles of induction. There were no 4-week mortalities and 4 (8.6%) 8-week mortalities. Deaths were attributed to subdural hemorrhage, multifactorial respiratory failure, progressive AML, and neutropenic sepsis. At a median follow up of 13.5 months, the overall survival is 12.4 months (95% CI:9.7-12.5). Conclusion We have shown that an induction regimen using decitabine as an epigenetic primer followed by cytarabine induces high CR/CRi rates with low treatment-related mortality in older adults with newly diagnosed AML who are not candidates for intensive chemotherapy, a patient population in whom there exists a dire need for novel treatment strategies. In the updated report of this phase 2 study, 69% of patients achieved a CR/CRi, and 4- and 8-week mortality were 0% and 8.6%, respectively. This compares favorably with historical outcomes of both intensive chemotherapy and decitabine monotherapy in older adults in terms of safety and efficacy, respectively. Overall survival was 12.4 months, which also compares favorably to previous reports of survival in this patient population. Methylation analyses at baseline and after decitabine in patients who achieved CR compared to patients who did not respond are ongoing and will be reported. We have demonstrated that decitabine followed by cytarabine is safe and effective in older adults with newly diagnosed AML. Disclosures No relevant conflicts of interest to declare.

Necrotizing Hemorrhagic Gastritis following Acute Myeloid Leukemia Induction with Midostaurin: An Unexpected Complication

2019 ◽  
Vol 143 (1) ◽  
pp. 65-68 ◽  
Author(s):  
Shai Shimony ◽  
Hilla Reiss Mintz ◽  
Yulia Shvartser Beryozkin ◽  
Avivit Shoham ◽  
Pia Raanani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Chemotherapy Regimen ◽  
Rare Complication ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Multikinase Inhibitor ◽  
Acute Myeloid ◽  
Count Recovery

Midostaurin is a tyrosine multikinase inhibitor approved for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) with mutated Fms-like tyrosine kinase-3. We describe a case report of a 49-year-old AML patient treated with an intensive chemotherapy regimen followed by midostaurin. After achieving complete remission with blood count recovery, he suffered from a serious, rare complication of necrotizing hemorrhagic gastritis with no evidence of infection or malignant infiltration, possibly associated with midostaurin therapy.

scholarly journals A Safety Study of the Addition of Omacetaxine to the Standard-of-Care Induction Regimen of Cytarabine and Idarubicin in Newly-Diagnosed AML Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5218-5218
Author(s):  
Sonia Christian ◽  
Kelley E. Kozma ◽  
Stephanie Barath ◽  
Ardaman Shergill ◽  
Damiano Rondelli ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Dose Level ◽  
Dose Escalation ◽  
De Novo ◽  
Standard Of Care ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Induction Regimen ◽  
Dose Levels

Abstract Background: Omacetaxine mepesuccinate (OM) is a semi-synthetic form of Homoharringtonine (HH), a cephalotaxine alkaloid. OM induces cell apoptosis by inhibiting peptide bond formation during mRNA translation, with rapid loss of short-lived proteins, such as MCL-1, c-MYC, and Cyclin D1 (Lu, J Hematol Oncol. 2014, 7: 2). Notably, cytarabine synergizes with HH in causing apoptosis of leukemia cells in vitro. A phase III RCT in China of 620 patients with de novo AML demonstrated superior CR and 3-yr survival rates upon addition of HH to a standard 2-drug AML induction therapy ('7 + 3'; Jin, Lancet Oncol. 2013, 14:599). Thus, we hypothesized that OM, at an appropriate dose, would similarly enhance the efficacy of a 7 + 3 regimen. OM is FDA-approved for the treatment of TKI-resistant CML. The MTD of 1.25 mg/m2/d SQ for 14 days every 28 days, as determined in a phase I/II CML trial of OM (Quintás-Cardama, Cancer 2007, 109: 248), served as a basis for the dose escalation used in this study. Methods: The primary endpoint of this phase I safety trial was to determine the optimally safe and active dose (OD) of OM when added to a standard 7 + 3 induction regimen, cytarabine and idarubicin. OM was administered SQ q12h d1-7 with cytarabine (100mg/m2 CIV) d1-7 and idarubicin (12mg/m2 IV) d1-3. Four dose levels were tested, starting with OM 0.625 mg/m2 q12h (further dose levels: 1.25, 2.0, 3.0, and 4.2 mg/m2 q12h). All newly diagnosed, untreated de novo or secondary AML patients, aged 18-70y with ECOG PS of 0-3 were eligible for this study. Secondary endpoints included overall response rate (ORR) and overall and event free survival (OS, EFS). Hematologic toxicity (HT) was defined as incomplete hematologic recovery; ANC < 1.0 x 109/L or platelet count < 100 x 109/L present at d49, with the bone marrow documented to be free of leukemic infiltration. Dose escalation was based on the EffTox design (Biometrics 2004, 60:684), a Bayesian adaptive design which considers the trade-off between efficacy and toxicity in determining the OD for Phase II trials. Results: Twenty-two patients, median age 58 (range 25-69) years were enrolled from June 2015 to June 2018. 12 patients (54.5%) had adverse cytogenetics, 6 (27%) intermediate risk, 3 (13.7%) favorable risk and 1 patient's cytogenetic risk was unknown (fibrotic BM). Eight patients demonstrated disease evolution from myelodysplastic syndrome (MDS). Altogether 16 of the 22 patients (73%) were deemed high risk based on cytogenetics or MDS-AML evolution. The EffTox design was implemented until cohort 4 (3 mg/m2 q12h), where 2 of 3 patients experienced a grade 5 non-hematologic toxicity (NHT), resulting in a dose-limiting toxicity (DLT). Since no DLTs were observed in cohort 3, an additional 5 patients were thus enrolled at this dose level to ensure safety. The OD was determined to be the dose level used in cohort 3: OM 2 mg/m2. No HTs were observed in 21 of 22 patients, (one patient not evaluable). The most common non-hematologic treatment emergent adverse events (TEAEs) of any grade were fever (68%), nausea (64%), vomiting (55%), hyperglycemia (41%), diarrhea (41%), mucositis (36%), headache (36%), sinus tachycardia (32%), rash/dermatitis (32%), and abdominal pain (32%). The most prevalent non-hematologic grade 3/4 TEAEs were febrile neutropenia (23%), hypoxia (18%), hyperglycemia (18%), and dyspnea (18%). ORR (CR and CRi) was 45.5%. Median OS was 605 days and EFS was 100 days. Conclusion: In this population with predominantly high-risk AML, the combination of OM with a standard 7 + 3 regimen demonstrates a manageable safety profile with acceptable efficacy. As ~ 25% of patients achieving CR with '7 + 3' do so after a second induction (based on meta-analysis of 6 trials, n = 1980, see Cancer 2010, 116: 5012), the ORR here is comparable to those receiving a single standard of care induction. The results in this high-risk group are therefore promising and warrant further investigation in a phase II trial. At present, we are assessing leukemic blast MCL protein expression in stored pre-treatment samples to determine if this predicts OM efficacy. NCT02440568. Teva has performed a Medical Accuracy Review of this abstract. Figure. Figure. Disclosures Khan: Teva: Speakers Bureau. Patel:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Honoraria.

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