Pegylated Interferon Alpha – 2a in Patients with Myeloproliferative Neoplasms (MPN): International Experience in 115 Cases

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2818-2818
Author(s):  
Krisstina Gowin ◽  
Prakash Thapaliya ◽  
J Samuelson ◽  
C N Harrison ◽  
Deepti Radia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
High Risk ◽  
Interferon Alpha ◽  
Research Funding ◽  
Pegylated Interferon ◽  
Pegylated Interferon Alpha ◽  
Clinical Records ◽  
Lost To Follow Up

Abstract Abstract 2818 Background: Pegylated interferon alpha-2a (Peg INF2a) has been demonstrated to be active therapy for high-risk essential thrombocythemia (ET) and polycythemia vera (PV), as well as treatment for early myelofibrosis (MF). We retrospectively analyzed the outcomes of Peg INF2a therapy in MPN patients treated outside the constraints of a clinical trial in the USA and EU. Methods: Clinical records of MPN patients treated at the participating centers, receiving Peg INF2a outside of the context of a clinical trial, were analyzed for response (ET and PV by ELN criteria; MF by EUNMET and IWG-MRT criteria), toxicity, and duration of response. Results: Patients: 115 patients were identified (54 PV (47%), 44 ET (38%), 17 MF (15%)) with a median age at diagnosis (48) and gender distribution (59% females) typical for the disorders. The patients had been diagnosed with the MPN a median of 44 months (0.0–312 months) prior to initiation of the Peg IFN2a and 64% harbored the JAK2-V617F mutation. The majority of patients (81%) had received at least one prior cytoreductive therapy for their disease (73 hydroxyurea, 39 anagrelide, 37 aspirin, 21 prior interferon (non pegylated), 3 phlebotomy alone). Therapy: Median starting dose of Peg INF2a was 45 micrograms/week (range: 22.5–180) with peak starting doses ranging from 30 to 300 micrograms/week. A total of 84 patients (73%) remain on Peg IFN2a with median duration of treatment of 17 months (range: 1.0–92). Toxicity: Overall the Peg INF2a was well tolerated. Hematological toxicity was Gr 3 or lower. There were 6 cases with anemia (5%), 10 with thrombocytopenia (9%) and 8 had leukopenia (7%). Most common non-hematologic toxicities were Gr 1–3 fatigue in 27 (23%), Gr 1 LFT elevation in 6 (5%), Gr 2–3 skin/allergic reaction in 6 (5%), Gr 1–2 nausea in 5 (4%), and Gr 2 mood disorder in 5 (4%) patients. Twenty patients (17%) discontinued therapy secondary to toxicity. Response: ET-PV: By ELN criteria, 30 PV patients achieved CR (55%), 17 achieved PR (31%), 4 achieved NR (7%), and 3 patients (5%) were lost to follow up or were too early to evaluate for response. In ET, the responses were CR in 27 (61%), PR in 7 (16%), NR in 4 (9%), and 6 patients (14%) were lost to follow up or were too early to evaluate for response. MF: The responses by IWG criteria were 1 CR (6%), 2 PR (12%), 2 CI (12%) and 9 SD (53%). By EUNMET, there were 2 CR (12%), 4 major responses (24%), 4 moderate responses (24%), 1 minor response (6%), 2 no response (12%), and 3 patients (17%) were lost to follow up or were too early to evaluate for response. Conclusions: Peg INF2a used at doses consistent with published clinical trials is active and well-tolerated when administered in a clinical setting outside of the support of a clinical trial. Given the majority of patients had previously failed cytoreductive therapy these results substantiate prior reports of efficacy of Peg INF2a in MPNs. Upcoming randomized clinical trials through the Myeloproliferative Disorders Research Consortium will help further define the role of Peg INF2a as first line therapy in high-risk MPNs. Disclosures: Mesa: Incyte: Research Funding; Lilly: Research Funding; SBio: Research Funding; Astra Zeneca: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding.

Pegylated Interferon Alpha-2a in 75 Patients with Myeloproliferative Neoplasms: A Single Center Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2818-2818 ◽  
Author(s):  
Krisstina L. Gowin ◽  
Tania Jain ◽  
Heidi E. Kosiorek ◽  
John Camoriano ◽  
Raoul Tibes ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Complete Remission ◽  
Interferon Alpha ◽  
Research Funding ◽  
Progressive Disease ◽  
Pegylated Interferon ◽  
Response Criteria ◽  
Hematologic Toxicity ◽  
Minor Response ◽  
Pegylated Interferon Alpha

Abstract Background: Pegylated interferon alpha-2a (Peg INF2a) has been demonstrated to be active therapy for high-risk essential thrombocythemia (ET), polycythemia vera (PV), and early myelofibrosis (MF). We retrospectively analyzed the outcomes of Peg INF2a therapy in myeloproliferative (MPN) patients treated outside the constraints of a clinical trial. Methods: Charts were analyzed for demographic and clinical data. Toxicity to therapy was assessed per CTCAE 3.0 criteria. Therapeutic responses for ET and PV were calculated by the revised ELN/IWG-MRT criteria including complete remission (CR), partial resmission (PR), no response (NR), or progressive disease (PD). Responses in MF were calculated by EUNMET: complete response (CR), major response (MR), moderate response (MoR), minor response (MiR) and NRand the revised IWG-MRT/ELN criteria: CR, PR, clinical improvement (CI), stable disease (SD) or PD. Results: Patients: 75 patients were identified overall. There were 36 PV patients (48%), 20 ET patients (26.7%), and 19 MF patients (25.6%). Thirteen MF patients were post-PV/ET MF. The median age at diagnosis was 51.5 yrs (range 28.8-75.1). JAK2 V617 mutation was present in 53 patients (70.7%). Median baseline hemoglobin (g/dL), leukocyte (x10 9), and platelet count (x109) for PV was 13.6, 8.6, 369, for ET was 12.5, 6.8, 517, and for MF was 11.4, 8.0, and 420, respectively. DIPSS risk category for the 19 MF patients: Low in 6 (31.5%) patients, Intermediate-1 in 3 (15.7%), Intermediate-2 in 8 (42%), and High in 2 (10.5%) patients. The majority of patients (82.2%) had received at least one prior cytoreductive therapy for their disease. Therapy: Median starting dose of Peg INF2a was 45 micrograms/week (range 45-90). The median peak dose was 90 micrograms/week (range 45-270). The median tolerated dose was 60 micrograms/week (range 5.6-180). The median duration of treatment was 24 months (range 3.6-85). Toxicity: Overall the Peg INF2a was well tolerated. Hematological toxicity included: leukopenia at grade 1 in 13 patients (17.3%), grade 2 in 5 patients (6.7%), and grade 3 in 1 patient (1.3%), anemia at grade 1 in 10 patients (13.3%) and grade 2 in 1 patient (1.3%), thrombocytopenia at grade 1 in 13 patients (17.3%) and grade 2 in 1 patient (1.3%). The most common non-hematologic toxicity included: fatigue at grade 1 in 14 patients (18.7%) and grade 2 in 4 patients (5.3%), transaminitis at grade 1 in 6 patients (8%) and grade 2 in 3 patients (4%), myalgias at grade 1 in 4 patients (5.3%). Response: See Table #1 PV/ET: 56 patients were evaluated by ELN/IWG-MRT criteria overall: A complete remission (CR) was seen in 8 patients (14.3%), a partial remission (PR) in 18 patients (32.1%), either a CR or PR in 18 patients (32.1%) when histologic remissions were unable to be documented due to lack of restaging bone marrow examination, no response in 11 patients (19.6%), and progressive disease in 1 patient (1.8%). Of the 12 patients receiving at least1 phlebotomy per month, 10 patients (83.3%) became phlebotomy independent with therapy. Of the 20 ET patients, 12 patients (60%) had platelet normalization (<400 x 109). MF: 19 patients were evaluated by IWG-ELN criteria: a PR was seen in 2 patients (10.5%), CI in 4 patients (21.1%), SD in 12 patients (63.2%), and PD in 1 patient (5.3%). Utilizing EUNMET critieria: 1 patient (5.3%) with a CR, 5 patients (26.3%) with a MR, 3 patients (15.8%) with MoR, 5 patients (26.3%) with MiR, and 5 patients (26.3%) with NR. Table 1. Peg INF2a Patient Responses RESPONSE Disease IWG-ELN response criteria: (Patient #, %) (Barosi, Blood 2013, Tefferi, Blood 2013) EUMET response criteria: (Patient #, %) (Barosi, Blood 2005) PV: N=36 CR: 3 pts (8.3%) PR: 14 pts (38.8%) CR/PR: 14 pts (38.8%) NR: 5 pts (13.8%) PD: 0 NA ET: N=20 CR: 5 pts (25%) PR: 4 pts (20%) CR/PR: 4 pts (20%) NR: 6 pts (30%) PD: 1 (5%) NA MF: N=19 IWG-ELN: PR: 2 pts (10.5%) CI: 4 pts (21.1%) SD: 12 pts (63.2%) PD: 1 pt (5.3%) EUNMET: CR: 1 pt (5.3%) MR: 5 pts (26.3%) MoR: 3 pts (15.8%) MiR: 5 pts (26.3%) NR: 5 pts (26.3%) NA: Not applicable Conclusions: Peg INF2a is active and well-tolerated when administered outside of the support of a clinical trial. Given the majority of patients had previously failed cytoreductive therapy these results substantiate prior reports of efficacy of Peg INF2a in MPNs. Disclosures Mesa: Pfizer: Research Funding; Gilead: Research Funding; Promedior: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; NS Pharma: Research Funding; Genentech: Research Funding.

Histomorphological Responses after Therapy with Pegylated Interferon Alpha-2a in Patients with Essential Thrombocythemia (ET) and Polycythemia Vera (PV)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4266-4266
Author(s):  
Lucia Masarova ◽  
C. Cameron Yin ◽  
Jorge E. Cortes ◽  
Marina Konopleva ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Response Assessment ◽  
Pegylated Interferon ◽  
Treatment Discontinuation ◽  
Molecular Response ◽  
Pegylated Interferon Alpha ◽  
Normal Morphology

Abstract Introduction: We previously reported the long-term efficacy and safety of pegylated interferon alpha-2a (PEG-IFN-a-2a) in 83 patients with ET and PV after a median follow-up of 83 months. Here, we present the bone marrow (BM) response assessment according to modified International Working Group for-Myeloproliferative Neoplasms Research and Treatment (IWG-MPN). Objective: To identify histomorphological BM responses in patients with ET and PV treated with PEG-IFN-a-2a as part of a prospective phase II study. Methods: All patients had BM assessment done prior to their enrollment, and then every 6-12 months while on study if possible, and in some patients after treatment discontinuation. Complete BM remission (BM-CR) required absence of > grade 1 reticulin fibrosis and disappearance of megakaryocyte hyperplasia in ET or trilinear hyperplasia with age-adjusted normocellularity in PV. An incomplete, partial response (BM-PR), was defined when fibrosis grading had consistently improved by at least one grade level on at least 2 consecutive samples > 12 months apart, yet with persistent MPN morphological features. Hematologic (HR) and molecular response (MR) assessments were previously reported (ASH 2015, abstract #60). Results: Among 83 enrolled patients (43 PV, 40 ET), 58 patients (70%) had evaluable BM samples for histomorphological response assessment, with median number of 8 samples per patient (range, 3-12). Among the remaining 25 patients, 18 were treated ≤12 months, and 7 did not have representative samples. Median age was 52 years (range, 19-75), and 29% (n=17) were males. Median disease duration prior to enrollment was 31 months (range, 1-350), and the median exposure to PEG-IFN-a-2a was 80 months (range, 15-107). After a median follow-up of 84 months (range, 36-107), 32 patients are on study. Forty-two patients were JAK2 positive, 6 CALR positive, 2 MPL positive and 8 triple negative (TN). Hematologic and molecular (JAK2V617F mutation only) responses were seen in 54 (93%) and 29 (69% of JAK2V617F positive) patients, including complete HR and complete MR in 52 (90%) and 9 (31%) patients, respectively. In total, 29 evaluable patients (50%) had BM response, including 13 patients (22%) with BM-CR (MF-0 in 11, example in Figure 1). Among 16 patients with BM-PR, 3 had resolution of dense collagen bundles as well as decreased reticulin fibrosis. Except for increased platelets in those with BM-PR (p<0.001), likely due to the higher proportion of ET patients in that group, no other differences in basic demographic or clinical parameters were present among different response groups (Table 1). Patients with BM response (PR & CR) had lower discontinuation rate, higher duration of response (HR & MR) with longer time on therapy; 13 patients with BM-CR had higher probability of complete MR (Table 1). Median time to BM-CR was 48 months (range, 30-72), median duration was 30 months (24-52), and has been maintained in 9 patients (69%). Two patients who lost their BM-CR are still on active therapy with persistent complete MR. Interestingly, 4 patients achieved BM-CR after being off therapy for a median of 18 months (range, 2-30), and 3 of them have sustained the BM-CR for 24, 50 and 52 months. Conclusions: Histomorphological BM responses (including complete response) can occur in ET/PV patients treated with PEG-IFN-a-2a, and generally correlate with more durable treatment benefit. Complete BM responses may be sustained even after treatment discontinuation, or be seen after therapy discontinuation. Despite this, we could not identify a uniform correlation between hematologic, histomorphological and molecular response. Table Patients with BM assessment stratified by response, N=58 Table. Patients with BM assessment stratified by response, N=58 Figure BM assessment of a PV patient with BM-CR. A & C: Before treatment: increased cellularity and abnormal megakaryocytes number/morphology; MF-2. B & D: After treatment: normocellular BM, normal morphology, MF-0. Figure. BM assessment of a PV patient with BM-CR. A & C: Before treatment: increased cellularity and abnormal megakaryocytes number/morphology; MF-2. B & D: After treatment: normocellular BM, normal morphology, MF-0. Disclosures Cortes: ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding.

Efficacy and Safety of Pegylated Interferon Alpha-2a in Patients with Essential Thrombocythemia and Polycythemia Vera: Results after a Median 7-Year Follow-up of a Phase 2 Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 60-60 ◽  
Author(s):  
Lucia Masarova ◽  
Srdan Verstovsek ◽  
Keyur P. Patel ◽  
Kate J Newberry ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Interferon Alpha ◽  
Essential Thrombocythemia ◽  
Research Funding ◽  
Pegylated Interferon ◽  
Molecular Remission ◽  
Molecular Responses ◽  
Pegylated Interferon Alpha ◽  
Allele Burden

Abstract Introduction: It has been previously reported that pegylated interferon alpha-2a can induce hematologic and molecular responses in patients with essential thrombocythemia "ET" and polycythemia vera "PV", but the follow up in these studies were relatively short. Objective: We present longer-term efficacy and safety results of a prospective phase II study of pegylated interferon alpha-2a in patients with ET and PV after a median follow up of 82.5 months (range, 8-107). Methods: Patients with a diagnosis of ET or PV, in a need of therapy, either newly diagnosed or previously treated, were eligible for this study. Median interferon starting dose of 180 mcg/week SQ (range, 450-90; 39% started on 90mcg/week) was modified in majority of the patients based on toxicity or lack of efficacy. Clinical and molecular responses were assessed every 3 to 6 months. Results: Among 83 enrolled patients (43 PV, 40 ET), 32 patients (39%) are still on study (but in 8 therapy is on hold: 5 due to toxicity, and 3 for financial reasons). Median age was 53 years (range, 19-78). Overall 37% of patients did not receive prior cytoreductive treatment. The overall median exposure to therapy was 87 months (range, 58-107) and was no different for patients still enrolled on the study and those who stopped study participation. Nine (28%) patients still on study are currently on a dose equal or higher than 90 mcg/week and 15 (47%) are on dose equal or smaller than 45mcg/week. JAK2 status or allele burden had no impact on achievement of response (clinical or molecular), time to response or duration of therapy. 55 of 59 (71%) JAK2V617F positive patients were evaluable for molecular response (Figure); 8 patients carried CARL mutation, 3 carried MPL and in 13 were triple negative. Median duration of hematologic and molecular response was 66 and 53 months, respectively; and directly correlated with treatment length and type of response (CMR had the longest duration of response). Overall yearly discontinuation rate were gradually decreasing for first 5 years, from 17% to 5%, and slowly increasing afterward to 10%. Of the 51 patients not on the study anymore, 27 (35% of the total) discontinued therapy primarily due to treatment toxicity. New late (≥24 months from start of therapy) G3/4 toxicity occurred in 17% of patients. Among patients in complete hematologic response treatment failure due to vascular adverse event or disease transformation was seen in 5 patients each. Three patients died on study (not related to therapy or disease), and 8 after stopping participation. Mean changes in allele burden over time in JAK2 positive patients are depicted in figure. Conclusions: Although pegylated interferon alpha-2a can induce significant hematologic and molecular responses; toxicity still limits its use over longer period of time and loss of response or transformation is encountered. Table.ResponseCharacteristicsFirst responseLast responseHem Resp, N. of patients (No), (%)CHR62 (76)25 (40)aPHR4 (5)1 (25)ORR66 (79)26 (39)aMol Resp, No, (%)CMR10 (18)9 (90)PMR20 (36)5 (25)*mMR5 (9)2 (40)ORR35 (74)16 (46)SafetyAny gradeGrade≥3Overall Adverse Events (AE), No, (%)any AE83 (100)57 (67)recurrent AE74 (89)13 (16)AE subtypes, No, (%)musculoskeletal73 (88)6 (8)neurological53 (64)2 (4)psychiatric38 (46)4 (11)gastrointestinal54 (65)11 (20)LFT elevation27 (33)5 (18)skin18 (22)2 (11)infection/fever26 (31)3 (12)respiratory23 (28)2 (9)cardiovascular13 (16)3 (23)metabolic16 (19)2 (13)neutropenia37 (45)21 (57)thrombocytopenia18 (22)a1 (6)anemia36 (43)1 (3)Autoimmune toxicity, No, (%)hepatitis1 (2.5)CNS vasculitis1 (2.5)lupus nephritis1 (2.3)Sjogren sy & dermatitis1 (2.5)Vascular AE (TEE/bleeding),Unprovoked6 (7)5 (83)No, (%)Provoked4 (5)3 (75)Disease transformation, No, (%)Myelofibrosis6 (7)AML1 (1)Safety over ≥24 months**Any gradeGrade≥3New AE, No (%)3th year10 (17)4 (40)4th year6 (11)4 (67)5th year5 (10)1 (20)≥ 6th year10 (24)1 (10)**Effective sample size for patients on therapy/year: Initial number of patients at risk at the beginning of period minus half of patients censored during that period*% calculated from 19 patientsastatistically significant differences by Fisher's exact testAbbr. CMR= complete molecular remission (undetectable JAK2 allele burden), PMR= partial molecular remission (>50% decrease in allele burden), mMR= minor molecular remission (20-49% decrease in allele burden) Figure 1. Figure 1. Disclosures Off Label Use: Pegylated Interferon alfa-2a used for patients with essential thrombocythemia and polycythemia vera. Cortes:Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; Teva: Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding.

Sex differences in depressive symptomatology in patients with chronic hepatitis C during pegylated interferon alpha therapy: A 72-week prospective study

2016 ◽  
Vol 33 (S1) ◽  
pp. S80-S80
Author(s):  
Z. Pavlovic ◽  
M. Jasovic-Gasic ◽  
D. Delic ◽  
N. Maric ◽  
O. Vukovic ◽  
...  
Keyword(s):  
Sex Differences ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Interferon Alpha ◽  
Depressive Symptomatology ◽  
Pegylated Interferon ◽  
Pegylated Interferon Alpha ◽  
Prevalence Of Depression

IntroductionTreatment with pegylated interferon alpha (PEG-IFN-α) is associated with depression more frequently in chronic hepatitis C (CHC) patients than with other inflammatory diseases.ObjectivesTo prospectively asses sex differences in the prevalence of depression in CHC patients during the PEG-IFN-α, as well as in the CHC group with no therapy.MethodsSample consisted of 103 subjects with CHC on the PEG-IFN-α and 103 subjects with CHC without interferon therapy. The diagnosis of depressive disorder was established by using Structured Clinical Interview and Criteria of International Classification Disorder. The severity of depression was assessed by using Hamilton Depression Rating Scale (HAMD ≥ 8) prior to PEG-IFN-α (baseline) and at the follow-up visits (4th, 12th, 24th, 48th, 72nd week).ResultsDuring the course of PEG-IFN-α, 49.5% of subjects showed depressive symptomatology (HAMD ≥ 8). Except at baseline and in the 72nd week, on the all other follow-up visits the prevalence of depression was significantly higher in female subjects (*all Ps < 0.05). The strongest difference was observed in the 12th week: of all the subjects with HAMD ≥ 8, 68.8% were female and 32.7% were male (P < 0.001). The multivariate logistic regression model showed that female sex is a very strong predictor for the development of depression during the interferon treatment [Exp (B) = 6.729]. There were no significant sex differences in the prevalence of depression in the control group.ConclusionsOur study (the longest study in this area) indicate that the prevalence of depression is significantly higher in female subjects with CHC during antiviral treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals The Prognostic Significance of Acquired 1q22 Gain in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Hadiyah Y. Audil ◽  
Joselle Cook ◽  
Patricia Greipp ◽  
Prashant Kapoor ◽  
Linda B Baughn ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Prognostic Significance ◽  
Advisory Board ◽  
Control Group ◽  
First Line ◽  
Advisory Committees

Background: Within the heterogeneous genomic landscape of multiple myeloma (MM), clonal evolution including the acquisition of risk-defining mutations and chromosomal abnormalities is a recurrent event and can be detected by fluorescence in situ hybridization (FISH). The effects of acquired abnormalities on clinical outcomes have not been well defined. We previously reported that patients who acquired 17p deletion [del(17p)] during the course of their disease had a significantly reduced overall survival (OS) by 38 months compared to patients who did not acquire del17p (Lakshman et al 2019). Similarly, while de novo gain of the long arm of chromosome 1 (1q22 gain) is a known high-risk aberration associated with significantly shorter OS and progression-free survival (PFS) in MM, the prognostic significance of acquired 1q22 gain has not been described. The primary objective of this study was to analyze factors predictive for acquired 1q22 gain and determine its impact on survival. Methods: We identified MM patients from the Mayo Clinic Dysproteinemia Database who had at least one follow up FISH performed ≥6 months from diagnosis. The clinical characteristics, concomitant cytogenetic abnormalities, first line treatments administered, and OS were compared between patients with acquired 1q22 gain and patients who did not acquire this abnormality. The Mayo Clinic IRB approved this study. Results: A total of 1041 MM patients met the inclusion criteria. Of these, 63 patients (6.1%) had acquired 1q22 gain, defined as being negative for 1q22 gain on initial FISH at diagnosis and having this abnormality detected on subsequent FISH. Median age at diagnosis was 59 years and 56% were male. Median time to acquisition of 1q22 gain was 60 months (range 8-140 months). We identified one control patient for each case who was diagnosed within one year of the case and had a subsequent FISH performed at a similar duration from diagnosis. Patients with acquired 1q22 gain had similar baseline characteristics except for a higher proportion of high-risk (HR) FISH at diagnosis [t(4;14), t(14;16), t(14;20), and del(17p13)] when compared to controls (27% HR FISH versus 6% HR FISH; P&lt;0.01). 1q22 gain was concomitantly present with trisomies in 33 patients (54%), monosomy 13 in 24 patients (39%), t(4;14) in 8 patients (13%), and del(17p13) in 7 patients (12%). All patients received treatment prior to acquisition of 1q22 gain. Of the 63 patients, first line induction therapy consisted of proteasome inhibitor (PI) with steroid in 43%, immunomodulatory drugs (IMiD) with steroid in 40%, and PI + IMiD with steroid in 17% of patients. 54 patients (85%) received upfront stem cell transplant (SCT) (median 5.9 months to SCT), compared to 50 patients (79%) in the control group who received SCT. The median follow up of all 126 patients was 6.8 years. There was a statistically significant reduction in median OS from diagnosis in patients with acquired 1q22 gain compared to the control group (10.8 years versus 13.0 years; P = 0.02; Figure 1). Predictors of acquisition of 1q22 gain were identified using a case-control method. Age ≥70 at diagnosis and presence of HR FISH at baseline appeared to increase the risk of acquiring 1q22 gain. Conclusion: Acquisition of 1q22 gain is a relatively uncommon occurrence, but notably reduced OS by 2.2 years compared to patients who did not acquire 1q22 during the course of their disease (P = 0.02). Older age and the presence of HR FISH at diagnosis increased the risk of acquisition of 1q22 gain. The presence of high-risk translocations at baseline suggests that acquisition of 1q22 gain occurs in the context of more aggressive disease biology. Disclosures Kapoor: Cellectar: Consultancy; Celgene: Honoraria; Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Dispenzieri:Alnylam: Research Funding; Pfizer: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Intellia: Research Funding; Janssen: Research Funding. Gertz:Prothena: Consultancy; Celgene: Consultancy; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Advisory Board for Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Advisory Board for Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Consultancy; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; NCI SPORE MM: Research Funding; Ionis/Akcea: Consultancy; Physicians Education Resource: Consultancy; Medscape: Consultancy, Speakers Bureau; Amgen: Consultancy; Appellis: Consultancy; Annexon: Consultancy; Spectrum: Consultancy, Research Funding; Janssen: Consultancy; Sanofi: Consultancy; Data Safety Monitoring board from Abbvie: Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy. Dingli:Apellis: Consultancy; Rigel: Consultancy; Millenium: Consultancy; Bristol Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding; Sanofi-Genzyme: Consultancy; Alexion: Consultancy; Janssen: Consultancy. Lin:Novartis: Consultancy; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy; Legend BioTech: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Kumar:Cellectar: Other; Genecentrix: Consultancy; Dr. Reddy's Laboratories: Honoraria; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; BMS: Consultancy, Research Funding; Sanofi: Research Funding; Karyopharm: Consultancy; MedImmune: Research Funding; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Novartis: Research Funding; Kite Pharma: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Adaptive Biotechnologies: Consultancy; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Merck: Consultancy, Research Funding; Carsgen: Other, Research Funding; Tenebio: Other, Research Funding.

scholarly journals Thyroid disturbances in children treated with combined pegylated interferon-alpha and ribavirin for chronic hepatitis C

2020 ◽  
Vol 63 (2) ◽  
pp. 52-55 ◽  
Author(s):  
Yasser K. Rashed ◽  
Fatma A. Khalaf ◽  
Sobhy E. Kotb
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Thyroid Function ◽  
Interferon Alpha ◽  
Pegylated Interferon ◽  
Thyroid Function Tests ◽  
Pegylated Interferon Alpha ◽  
Function Tests

Background: Immunomodulatory properties of interferon (IFN) have been documented. It may induce autoimmune diseases such as autoimmune thyroiditis with hypo- or hyperthyroidism. In addition, it may impair thyroid hormone synthesis through affecting iodide organification in thyroid gland.Purpose: The aim of this study was to describe thyroid function tests disturbances in children with chronic hepatitis C (CHC) receiving pegylated interferon-alpha (PEG IFN-α) plus ribavirin.Methods: Fifty children with CHC virus infection who received combined pegylated interferon-alpha with ribavirin were selected. Other 50 apparently healthy children of matched age and sex (considered as control group) were selected. All children (100) were subject to liver function tests, virological studies, and follow-up of thyroid function test during and after the treatment course.Results: Our study showed that 28% of children received combined PEG IFN-α plus ribavirin showed subclinical hypothyroidism. After 24 weeks treatment with combined therapy of IFN plus ribavirin, the mean level of thyroid stimulating hormone (TSH) was 3.23±88 mU/mL, while TSH was 1.16± 0.77 mU/mL before starting treatment. On the other hand, mean TSH was 1.09±0.92 mU/mL in normal control group.Conclusion: This study revealed an association between subclinical thyroid dysfunction and treatment with IFN-alpha and ribavirin in children. Further studies on larger number of patients and longer follow-up duration are recommended for further confirmation.

The Outcome of Patients (pts) with Chronic Myeloid Leukemia (CML) Treated with Imatinib Outside of a Clinical Trial or On a Clinical Trial At a Single Institution

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1693-1693
Author(s):  
Musa Yilmaz ◽  
Hagop M. Kantarjian ◽  
Elias J. Jabbour ◽  
Susan M. O'Brien ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Research Funding ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Single Institution ◽  
Free Survival ◽  
Excellent Outcome ◽  
Significant Difference

Abstract Abstract 1693 Background: Outcomes of CML chronic phase (CP) pts treated in clinical trials are frequently perceived to not be representative of those treated outside of clinical trials (Lucas et al, Haematologica 2009; 94: 1362–7). The latter is frequently referred to as “the real world” world experience. Some reports have suggested that outcome of pts treated outside of clinical trials have an inferior outcome. We investigated the outcomes of pts receiving imatinib on and off a clinical trial for CML-CP at a single institution. Methods: We reviewed the medical records of all pts with CML-CP treated at MDACC between 2000 and 2012 to identify pts that received initial therapy with imatinib 400 mg on a clinical trial or as standard therapy outside of a clinical trial (“off protocol” group). Only pts who had not received any prior therapy, or only hydroxyurea, or interferon alpha for less than 1 month, and that initiated on 400 milligram daily dose of imatinib within 6 months of diagnosis were included. Event-free survival (EFS) was measured from the start of treatment to the date of any of the following events: loss of major cytogenetic response (MCyR), loss of complete hematologic response (CHR), transformation to accelerated phase (AP) and blast phase (BP), and death while on imatinib. Transformation-free survival (TFS) was measured from the start of treatment to the date progression to AP/BP during therapy, last follow-up, or death from any cause. Overall survival (OS) was measured until death form any cause at any time. Results: We identified 65 pts treated with imatinib off protocol during the period of interest. During this time 71 pts were treated on clinical trials with imatinib. The median age was 49 yrs (15–79) for pts on clinical trials and 49 yrs (15–84) for those off protocol, respectively. The median follow-up was 125 months (13 to 142) for pts on clinical trials and 51 months (2 to 117) for those off protocol. The overall complete cytogenetic response (CCyR) rates were 84% and 83% for patients treated on and off protocol, respectively. CCyR rates, 12 months after initiation of imatinib, were not different (60% vs 66%, respectively; p=.15). Pts treated on protocol had higher rates of major molecular response (MMR) (79% vs 58%, P=.012) and complete molecular response (CMR = undetectable with sensitivity of at least 4 logs) (42% vs 32%, P=.045) at any time compared to the pts treated off protocol. This is likely due to the longer follow-up for pts on protocol as MMR takes longer to occur. In fact, the MMR rate at 12 months were 30% and 24% in pts treated on and off protocol, respectively (p=.28). Analyzing earlier responses, 3-month rates of MCyR were 71% on protocol and 69% off protocol (p=.82). Corresponding rates at 6 months were 82% and 85%, respectively (p=.68). The 5-year EFS rates were 86% and 84% for on and off protocol patients, respectively. There was also no significant difference in 5-year TFS (96% vs 94%) and OS (90% vs 96%). Conclusion: These results suggest that pts with CML treated outside of a clinical trial may have the same excellent outcome as those treated on a clinical trial provided they are followed with the same rigor. Disclosures: Ravandi: BMS: Research Funding. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.

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