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Does Therapy-Related Myelofibrosis Exist? Analysis of 1100 Myelofibrosis Cases from a Single Institution
Abstracts MPN-115 Does Therapy-Related Myelofibrosis Exist? Analysis of 1100 Myelofibrosis Cases from a Single Institution Lucia Masarova , Prithviraj Bose, Hagop Kantarjian, Srdan Verstovsek The University of Texas MD Anderson Cancer Center, Houston, TX, United States
Introduction: The association between prior other malignancies (OM) and myelofibrosis (MF) as well as the existence of therapyrelated myelofibrosis (t-MF) are largely unknown. Objective: To determine the occurrence of MF after a prior OM and its relationship with the therapeutic approach used for the OM. Methods: Fisher’s exact, Mann-Whitney and Kruskal-Wallis tests were used to compare categorical and continuous variables, respectively. KaplanMeier analysis and log-rank test were used to compare overall survival. Results: We performed a retrospective chart review of 1100 patients referred to our institution between 1984 and 2013 with a diagnosis of MF. Overall, 121 (11%) patients were found to have OM before MF. Median age at the time of MF diagnosis was 70 years (range, 35-89). Median lag time between OM and MF was 86 months (range, 3-563) and median follow-up from MF diagnosis was 31 months (range, 0.1-213). Twenty-three patients had more than 1 OM. The most common OM were prostate (30%), melanoma (17%), and colorectal carcinoma (10%). Surgery or hormonal manipulation therapy was used in 79 (65%) patients, chemotherapy in 25 (21%) and radiation in 17 (14%). Alkylating agents and topoisomerase II inhibitors were used, either as monotherapy or in combination, in 19 (76%) patients with chemotherapy exposure. OM subtype or primary therapeutic approach had no impact on MF occurrence. No significant differences in clinical parameters (CBC, LDH, transfusion dependence, unfavorable karyotype, major driver mutations) or incidence of AML were seen between patients treated with different primary therapies. Seventy-four percent of patients with OM-MF have died (n¼89) with similar median time to death for all groups: 25 months (range, 2-140). Known causes of death (37% of patients who died) included progression of MF (n¼11), OM (n¼5), multi organ failure (n¼10), and others (n¼7). Estimated median OS from MF was 45 months (range, 0.2-156) and was similar regardless of primary OM approach or subsequent MF therapy. Conclusion: In our experience, t-MF does not appear to exist.
Introduction: Other malignancies (OM) were reported to be increased in patients with essential thrombocythemia (ET) and polycythemia vera (PV). The effect of coexistent OM on the rate of disease transformation to MF is unknown. Objective: To determine the occurrence of OM in patients with ET and PV and their influence on transformation rate to overt MF. Methods: We perform a retrospective chart review of 783 patients with ET (n¼256), PV (n¼ 165), and Post ET/PV-MF (n¼362), who were referred to our institution between years 1960 e 2013. Fisher’s exact test, and Mann-Whitney test were used to compare categorical and continuous variable, respectively. Matched control group of patients without OM was used to compare transformation rates and overall survival (OS), expressed by Kaplan-Meier curve and long rank test. Results: Overall, 107 (13.7%) patients had OM prior to MF transformation with total of 125 cases. The most frequent OM observed were carcinomas of prostate, breast and gastrointestinal tract. Nine patients had more than 1 OM. Median age at diagnosis of MPN and OM were 59 and 62 years, 50% were males. After median follow up of 30 months (range, 1-150), 49 (46%) patients had died with OM related death in 11 patients (23%). No MPN related deaths were observed, however, 2 patients progressed to acute leukemia. No significant differences in demographics and clinical characteristics were detected among patients groups. Median overall survival from MPN of 160 months (range, 1-240) and overall time to transformation to MF (median 6 years, range 0.5-29) were similar between ET and PV, as well as control group. Conclusions: OM diagnosed after ET or PV does not seem to influence the rate of disease transformation to MF.
MPN-134 Superior Lethal Activity of Novel BRD4-Degrading Proteolysis Targeting Chimera (PROTACs) versus BET Protein Bromodomain Inhibitor (BETi) Against Post-Myeloprofilerative Neoplasm (MPN) Secondary AML Cells Kapil Bhalla , Dyana Saenz, Warren Fiskus, Taghi Manshouri, Baohua Sun, Christopher Mill, Srdan Verstovsek The University of Texas MD Anderson Cancer Center, Houston, TX, United States
MPN-116 Does Occurrence of Other Malignancy After Essential Thrombocythemia and Polycythemia Vera Influence their Rate of Transformation to Myelofibrosis? Lucia Masarova , Sherry Pierce, Jorge Cortes, Hagop Kantarjian, Srdan Verstovsek The University of Texas MD Anderson Cancer Center, Houston, TX, United States
Myeloproliferative neoplasm, myelofibrosis (MPN-MF), exhibits increased JAK-STAT signaling and often progresses (w15-20%) to AML (sAML). JAK inhibitor (JAK-I) ruxolitinib (Rux) or standard induction chemotherapy is only modestly active against sAML. sAML cells commonly exhibit JAK2V617F mutation, as well as mutations in TP53, TET2, ASXL1, IDH1&2, SRSF2, RUNX1, MYC, PTPN11, NRAS and SETBP1. Here, we compared the lethal activity of the novel PROTAC ARV-825 (Arvinas Inc.) with the BETi OTX-015 against cultured and primary sAML cells. ARV-825 recruits and utilizes the E3 ubiquitin ligase activity of Cereblon to degrade (through the
Clinical Lymphoma, Myeloma & Leukemia September 2016
- S93
Introduction: The association between prior other malignancies (OM) and myelofibrosis (MF) as well as the existence of therapyrelated myelofibrosis (t-MF) are largely unknown. Objective: To determine the occurrence of MF after a prior OM and its relationship with the therapeutic approach used for the OM. Methods: Fisher’s exact, Mann-Whitney and Kruskal-Wallis tests were used to compare categorical and continuous variables, respectively. KaplanMeier analysis and log-rank test were used to compare overall survival. Results: We performed a retrospective chart review of 1100 patients referred to our institution between 1984 and 2013 with a diagnosis of MF. Overall, 121 (11%) patients were found to have OM before MF. Median age at the time of MF diagnosis was 70 years (range, 35-89). Median lag time between OM and MF was 86 months (range, 3-563) and median follow-up from MF diagnosis was 31 months (range, 0.1-213). Twenty-three patients had more than 1 OM. The most common OM were prostate (30%), melanoma (17%), and colorectal carcinoma (10%). Surgery or hormonal manipulation therapy was used in 79 (65%) patients, chemotherapy in 25 (21%) and radiation in 17 (14%). Alkylating agents and topoisomerase II inhibitors were used, either as monotherapy or in combination, in 19 (76%) patients with chemotherapy exposure. OM subtype or primary therapeutic approach had no impact on MF occurrence. No significant differences in clinical parameters (CBC, LDH, transfusion dependence, unfavorable karyotype, major driver mutations) or incidence of AML were seen between patients treated with different primary therapies. Seventy-four percent of patients with OM-MF have died (n¼89) with similar median time to death for all groups: 25 months (range, 2-140). Known causes of death (37% of patients who died) included progression of MF (n¼11), OM (n¼5), multi organ failure (n¼10), and others (n¼7). Estimated median OS from MF was 45 months (range, 0.2-156) and was similar regardless of primary OM approach or subsequent MF therapy. Conclusion: In our experience, t-MF does not appear to exist.
Introduction: Other malignancies (OM) were reported to be increased in patients with essential thrombocythemia (ET) and polycythemia vera (PV). The effect of coexistent OM on the rate of disease transformation to MF is unknown. Objective: To determine the occurrence of OM in patients with ET and PV and their influence on transformation rate to overt MF. Methods: We perform a retrospective chart review of 783 patients with ET (n¼256), PV (n¼ 165), and Post ET/PV-MF (n¼362), who were referred to our institution between years 1960 e 2013. Fisher’s exact test, and Mann-Whitney test were used to compare categorical and continuous variable, respectively. Matched control group of patients without OM was used to compare transformation rates and overall survival (OS), expressed by Kaplan-Meier curve and long rank test. Results: Overall, 107 (13.7%) patients had OM prior to MF transformation with total of 125 cases. The most frequent OM observed were carcinomas of prostate, breast and gastrointestinal tract. Nine patients had more than 1 OM. Median age at diagnosis of MPN and OM were 59 and 62 years, 50% were males. After median follow up of 30 months (range, 1-150), 49 (46%) patients had died with OM related death in 11 patients (23%). No MPN related deaths were observed, however, 2 patients progressed to acute leukemia. No significant differences in demographics and clinical characteristics were detected among patients groups. Median overall survival from MPN of 160 months (range, 1-240) and overall time to transformation to MF (median 6 years, range 0.5-29) were similar between ET and PV, as well as control group. Conclusions: OM diagnosed after ET or PV does not seem to influence the rate of disease transformation to MF.
MPN-134 Superior Lethal Activity of Novel BRD4-Degrading Proteolysis Targeting Chimera (PROTACs) versus BET Protein Bromodomain Inhibitor (BETi) Against Post-Myeloprofilerative Neoplasm (MPN) Secondary AML Cells Kapil Bhalla , Dyana Saenz, Warren Fiskus, Taghi Manshouri, Baohua Sun, Christopher Mill, Srdan Verstovsek The University of Texas MD Anderson Cancer Center, Houston, TX, United States
MPN-116 Does Occurrence of Other Malignancy After Essential Thrombocythemia and Polycythemia Vera Influence their Rate of Transformation to Myelofibrosis? Lucia Masarova , Sherry Pierce, Jorge Cortes, Hagop Kantarjian, Srdan Verstovsek The University of Texas MD Anderson Cancer Center, Houston, TX, United States
Myeloproliferative neoplasm, myelofibrosis (MPN-MF), exhibits increased JAK-STAT signaling and often progresses (w15-20%) to AML (sAML). JAK inhibitor (JAK-I) ruxolitinib (Rux) or standard induction chemotherapy is only modestly active against sAML. sAML cells commonly exhibit JAK2V617F mutation, as well as mutations in TP53, TET2, ASXL1, IDH1&2, SRSF2, RUNX1, MYC, PTPN11, NRAS and SETBP1. Here, we compared the lethal activity of the novel PROTAC ARV-825 (Arvinas Inc.) with the BETi OTX-015 against cultured and primary sAML cells. ARV-825 recruits and utilizes the E3 ubiquitin ligase activity of Cereblon to degrade (through the
Clinical Lymphoma, Myeloma & Leukemia September 2016
- S93