Persistent Molecular Remission in Patients Treated with Imatinib-IFNa Combination or Imatinib Monotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4784-4784
Author(s):  
Monica Schippa ◽  
Enrico Gottardi ◽  
Debora Luzi ◽  
Lorenzo Falchi ◽  
Rita Emili ◽  
...  
Keyword(s):  
Real Time ◽  
Small Sample Size ◽  
Philadelphia Chromosome ◽  
Small Sample ◽  
Molecular Response ◽  
Second Line ◽  
Molecular Remission ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Line Of Therapy

Abstract INTRODUCTION. Continously improving results have been obtained during the last two decades in the control of Philadelphia chromosome (Ph’) positive chronic myeloid leukemia (CML). However, the final goal of molecular remission remains difficult to be obtained, even in the imatinib era. AIMS: Evaluation of the rate of long lasting molecular remission (undetectable p210 transcript at RQ-PCR confirmed by NESTED/RT-PCR in at least two subsequent tests performed over a period of 12 months or more) in response to imatinib or to imatinib-IFNa combination employed as first, second or subsequent line of therapy. PATIENTS. Imatinib alone or in combination with IFNa was given as first, second or subsequent line of therapy to a total of 47 patients. In particular, twenty-one patients were treated at the time of diagnosis with imatinib alone (18,G1) or imatinib-pegilated IFN combination (3,G2). Twenty-three additional patients (G3) received imatinib as second line therapy. Finally, 11 patients were treated with the imatinib-IFNa combination as second (5,G4) or third (6,G5) line therapy. In details, G4 consisted of three patients in cytogenetic relapse (3) or no response (2) after first line imatinib (1)or IFNa-ARA-C(1)therapy. All six patients included in G5 were complete kariotypic, but not molecular responder to imatinib given as second line treatment. METHODS. Molecular response was evaluated by NESTED/real-time-PCR (Guo JQ et al.; Leukemia : 2002; 15:2447–53) and real-time quantitative-PCR (Gabert J et al. Leukemia : 2003; 17: 2318–57) time intervals of 3–6 months from the beginning of therapy. RESULTS. A complete molecular remission lasting 12 months or more was obtained in 11 of 42 evaluable patients(therapy duration ≥ 18 mths).The response rate was higher in patients receiving the imatinib-IFNa combination(6/14) than in those given imatinib in monotherapy (5/36).In details, 4/14 and 1/3 patients respectively receiving early imatinib or imatinib-IFNa combination achieved a stable molecular remission. Two to four consecutive negative tests were documented in all five cases over a period ranging from 12 to 19 mths with 4 patients still in continous remission. Furthermore, 1/22 and 5/11 patients obtained a complete molecular response to imatinib given as second line therapy or imatinib-IFNa combination employed as second (4) or third (1) line therapy. Five negative tests were documented over a period of 12 mths in the patient responsive to imatinib monotherapy. Three to 7 negative consecutive tests were obtained during a period of 12 to 36 mths in the remaining five cases while receiving the imatinib-IFN-a combination. At the present time, 5 of these 6 patients are in continous molecular remission. In all molecularly responsive patients, stable molecular remission was usually preceded by a period of fluctuating negative-positive results of NESTED-PCR tests. CONCLUSIONS. It is not possible to achieve any firm conclusion regarding the effect of the imatinib-INFa combination on molecular response because of the small sample size of treated patients. However, our findings suggest an additive effect of imatinib and IFNa in Ph’ clone control as indicated by the improvement of the quality of remission in long lasting kariotypically, but not molecularly responsive patients when this combination therapy was utilized.

Molecular remission to imatinib-IFN-alpha combination or imatinib monotherapy in chronic myeloid leukemia (CML) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17512-17512
Author(s):  
A. Liberati ◽  
M. Schippa ◽  
D. Luzi ◽  
L. Falchi ◽  
R. Emili ◽  
...  
Keyword(s):  
Philadelphia Chromosome ◽  
Small Sample ◽  
Molecular Response ◽  
Second Line ◽  
Rt Pcr ◽  
Molecular Remission ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Remission Duration ◽  
Line Of Therapy

17512 Background: Continously improving results have been obtained in the control of Philadelphia chromosome (Ph’) positive CML. However, the final goal of molecular remission remains difficult to be obtained, even in the imatinib era. Evaluation of the rate of complete molecular remission (undetectable p210 transcript at RQ-PCR confirmed by NESTED/RT-PCR in at least two subsequent tests over a period of 3 mths or more) to imatinib or to imatinib-IFNa combination as first, second or subsequent line of therapy. Imatinib alone or in combination with IFNa was given as first, second or subsequent line of therapy to a total of 47 patients. In particular, 21 patients were treated at the time of diagnosis with imatinib alone (18,G1) or imatinib-pegilated IFN combination (3,G2). Twenty-three additional patients (G3) received imatinib as second line therapy. Finally, 13 patients were treated with the imatinib-IFNa combination as second (7,G4) or third (6,G5) line therapy, but in two cases IFNa was discontinuated after one month because of intolerance to treatment. Methods: Molecular response was evaluated by NESTED/RT-PCR (Guo JQ et al.; Leukemia:2002;15:2447–53) and RQ-PCR (Gabert J et al. Leukemia:2003;17:2318–57) at time intervals of 3–6 months from the beginning of therapy. Results: Complete molecular remission lasting 3 months or more (range 3–34) was obtained in 15 of 44 evaluable patients (therapy duration = 11 mths, range 11–73).The response rate was higher in patients receiving imatinib- IFNa combination given as first or second line therapy (5/13) than in those given imatinib monotherapy (9/37). In 7 of the 15 complete responders, remission duration lasted more than 12 mths (range 12–34) with 6/7 pts still continuous remission. In further 6 cases continuous remission duration ranged from 3–8 mths while in one case fluctuating negative-positive NESTED/RT-PCR tests have been observed over a period of 65 months. Conclusions: It is not possible to draw any firm conclusion regarding the effect of the imatinib-INFa combination on molecular response because of the small sample size of treated patients. However, our findings suggest an additive effect of imatinib and IFNa in Ph’positive clone control. No significant financial relationships to disclose.

Philadelphia Chromosome (Ph’) Secondary Clones in Chronic Myeloid Leukemia (CML) Are Not Indicative of Resistance to IFNa- or Imatinib-Based Treatment Regimens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4806-4806
Author(s):  
Lorenzo Falchi ◽  
Paolo Prontera ◽  
Debora Luzi ◽  
Viola Festuccia ◽  
Rita Emili ◽  
...  
Keyword(s):  
Real Time ◽  
Small Sample Size ◽  
Clonal Evolution ◽  
Philadelphia Chromosome ◽  
Small Sample ◽  
Molecular Response ◽  
Molecular Remission ◽  
Trisomy 8 ◽  
Real Time Quantitative Pcr ◽  
Treatment Regimens

Abstract The rate of complete karyotypic remission (CKR) and complete molecular remission (undetectable BCR/ABL specific transcript by real-time quantitative-PCR (Gabert J et al. Leukemia: 2003; 17: 2318–57) and NESTED/real-time-PCR (Guo JQ et al.; Leukemia: 2002; 15:2447–53)) to various therapies was analysed in 35, of the 114 CML patients observed in our institution, who showed cytogenetic clonal evolution. Overall, 52 karyotypic abnormalities additional to Ph’ were documented at the time of diagnosis (early clonal evolution) or late in the course of the disease (late clonal evolution). Seven of 12 patients with early clonal evolution achieved one (5 pts) or more (2 pts) CKRs, for a total number of 9, in response to IFNα (2 CKRs), IFNα plus ARA-C (1 CKR), imatinib (5 CKRs) or imatinib-IFNα combination (1 CKRs). Six of the 23 patients with late clonal evolution achieved one or more CKRs during the course of their disease after treatment with IFNα (2), IFNa plus ARA-C (1) or imatinib (5). In addition, 7 of the 13 CK responders reached a complete molecular remission in response to IFNa (1), IFNa plus ARA-C (1) imatinib (1), or imatinib plus IFNa (4). The 5 complete molecular remissions documented in patients with early clonal evolution, were observed following treatment with IFNα plus ARA-C (1), imatinib (1), or imatinib plus IFNα (3). Two patients with late clonal evolution obtained complete molecular remission in response to IFNα and imatinib plus IFN therapy, respectively. Cytogenetic and molecular response rates were higher in patients with early (58%, 57%) than in patients with late secondary clones (26%, 33%), while there were no significant differences in time to achieve cytogenetic (2–20 months vs 1–25 months) or molecular (3–26 months vs 13–52 months) remission and the duration of response (11 months, range 4–42 vs 10 months, range 7–46 and 2–19 vs 3–13+ months, respectively) between the two groups. Finally, no relationship was evident between the type of additional karyotypic anomalies and sensitivity to treatment. In fact, clones bearing complex translocations (2), isoPh’ (2), trisomy 8 (2), translocations other than Ph’ (2), partial chromosome monosomy (11-q, 1) or loss of chromosome Y alone (1) or associated with other anomalies (−6 and −14 or −21 or isoPh’) (3) all responded to therapy. In conclusion, although the small sample size, these findings suggest that the presence of karyotypic abnormalities additional to Ph’ in CML is not associated to disease resistance to therapy.

Comparasion Between Nilotinib and Dasatinib as Second-Line Therapy for Patients with Chronic Myeloid Leukemia: A Single Center Retrospective Study.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3440-3440
Author(s):  
Clarisse Lobo ◽  
Carla Boquimpani ◽  
Tania Silva Madeira ◽  
Patricia Wendling ◽  
Claudia Maximo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Randomized Clinical Trials ◽  
Molecular Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Abstract Abstract 3440 Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors (TKI) used in patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. There are no randomized clinical trials comparing these drugs in this context. The aim of this study was to compare, retrospectively, the hematological, cytogenetic and molecular response in patients submitted to these second-generation TKI at Hemorio, a public brazilian institution. A total of 114 patients were analyzed, 63 received nilotinib and 51 dasatinib as second-line therapy (55.3% and 44.7%, respectively). The following variables were equally distributed between these two groups (nilotinib vs. dasatinib, respectively): male sex (54% vs. 60.8%, p=0.46), median age at diagnosis (46 vs. 45 years, p=0.76), median time in months using imatinib before the switch (45.2 vs. 44.1, p=0.96), resistance to imatinib (98.4% vs. 98%, p=0.88), presence of the mutation T315I (3.2% vs. 3.9%, p=0.09), patients in chronic phase before the switch (85.7% vs. 86.3%, p=0.93). Use of another second generation TKI, as a third-line therapy, was necessary in 30 out of the 114 patients analyzed (26.1%) because of lack of response. This modification was slightly more frequent in the group initially submitted to nilotinib (31.7% vs. 19.6%, p=0.21). Patients who used a third-line therapy were excluded from response and survival analyzes. Response rates after the second-generation TKI were similar between these two groups (nilotinib vs. dasatinib): complete hematological response until three months (77.8% vs. 87.3%, p=0.24), complete cytogenetic response until six months (21.6% vs. 22.2%, p=0.95) and 12 months (32.4% vs. 33.3%, p=0.94) and major molecular response reached before 12 months (32.7% vs. 21.6%, p=0.25). Two-year overall survival (OS) and progression free-survival (PFS) were similar between these two groups (nilotinib vs. dasatinib, respectively): 92.2% vs. 87.8% (p=0.38) for OS and 87.8% vs. 83.7% (p=0.14) for PFS. Although not statistically significant, two-year OS was inferior in the group of patients who needed a third-line therapy (70.5% vs. 95.6%, p=0.70). Our results suggest that the response and survival rates are similar between nilotinib and dasatinib as second-line therapy for patients with imatinib resistant or intolerant CML. Also, they suggest an inferior prognosis for patients who need a third-line therapy. In this way, the choice between these two TKI for second-line therapy should be guided by the clinical characteristics and the mutation status of the patient. Disclosures: Lobo: NOVARTIS: Research Funding.

Bortezomib-Dexamethasone Alone or Plus Cyclophosphamide or Lenalidomide As Second-Line Treatment for Patients with Multiple Myeloma: Final Results From a Phase 2 Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1861-1861
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Meral Beksac ◽  
Lotfi Benboubker ◽  
Huw Roddie ◽  
Nathalie Allietta ◽  
...  
Keyword(s):  
Response Rate ◽  
Stage Migration ◽  
Second Line ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Line Of Therapy

Abstract Abstract 1861 Background: Bortezomib plus dexamethasone (VD) has been shown to be effective and well tolerated in patients (pts) with multiple myeloma (MM) as frontline induction therapy and in relapsed pts; however, no studies have prospectively assessed VD as second-line therapy. The addition to VD of cyclophosphamide (VDC) or lenalidomide (VDR) may improve efficacy, but with increased toxicities. This phase 2 study evaluated the efficacy and safety of VD, with the addition of C or R for pts with stable disease (SD) after 4 cycles, in pts with relapsed or refractory MM following 1 prior line of therapy. This is the first prospective study of VD as second-line therapy for MM. Methods: Bortezomib-naïve pts aged ≥18 years with measurable MM and no grade ≥2 peripheral neuropathy (PN) who had relapsed/progressed after 1 previous line of therapy received four 21-day cycles of VD (bortezomib 1.3 mg/m2, days 1, 4, 8, 11; Dex 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12). Pts achieving at least partial response (PR) then received a further 4 cycles of VD. Pts with SD were randomized to a further 4 cycles of VD, or 4 cycles of VDC (VD + C 500 mg, days 1, 8, 15), or VDR (VD + R 10 mg, days 1–14) for Cycles 5–8. Pts with progressive disease (PD) discontinued treatment. The primary end point was response rate; secondary end points included time to response, duration of response (DOR), safety, and improvement in renal function (defined by the Cockcroft-Gault glomerular function rate [GFR], assessed prior to treatment on day 1, Cycles 1–5). Results: A total of 189 pts were enrolled; 26 did not receive therapy and were excluded from the safety/ITT population (N=163). Median age was 63 years (range 34–86), 53% were male, 20% had KPS ≤70; median time from prior therapy was 13.9 months. In the ITT population, 52% of pts (84/163) experienced an OR by Cycle 4 as validated by IDMC. Discontinuations were due to toxicity (N=10), death, PD, and other reasons (6 each). Of 135 remaining pts who started Cycle 4 treatment, 120 pts had a response assessment at Cycle 4; according to investigators, 82% of these pts experienced an overall response (OR) and 2.5% had PD; median time to first and best response was 49 and 85 days, respectively. Nineteen pts had SD and were randomized: 7 to VD, 8 to VDC (1 did not continue treatment), 4 to VDR. Only 11 pts received a third drug, C or R, in addition to VD. Due to the high response rate for the first four cycles, the second randomization arm was not completed. 47% (77/163) had continued treatment up to Cycle 8. Based on IDMC response validation as of June 2011, 122 patients had a Best Confirmed Response: 75% OR, 20% SD, and 4% PD. GFR results at Cycle 8 are shown in the Table. In pts who had baseline and on-study assessments, median GFR was 62.2 mL/min at baseline and increased after Cycles 1, 2, 3, 4, 5, 6, 7, and up to Cycle 8 by 4.5, 5.7, 9.4, 8.7, 6.0, 9.6, 8.9, and 5.5 mL/min, respectively. Of the 26 pts with stage migration from baseline GFR to best GFR at Cycle 4, 12 had a renal response (MR renal). Of the 24 pts with baseline GFR <50 ml/min and renal response with stage migration from baseline GFR to best GFR at Cycle 8, 13 had CR renal, 11 had MR renal. Grade 3/4 adverse events (AEs) occurred in 64% of pts; the most common were thrombocytopenia (17%), anemia (10%), and constipation (6%). 40% of pts had serious AEs, and 46%/29%/12% had AEs resulting in dose reductions/discontinuation/death. Overall rates of sensory PN, polyneuropathy, PN (neuropathy peripheral), and motor PN in Cycles 1–8 were 20%, 18%, 13%,and 1% respectively, including 5%, 5%, 4%, and 1% grade 3/4, respectively; 55% of PN events were reversible, with resolution in 43%. Conclusions: This is the first prospective trial which assessed VD as second-line treatment in MM. VD is effective and well tolerated with less than 10% of pts receiving subsequent C or R added to VD. Overall renal function was shown to improve with treatment. PN was manageable with good reversal rates. VD represents a feasible, active treatment option for pts with relapsed MM. Final efficacy and safety data will be presented. Disclosures: Dimopoulos: Ortho Biotech: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc: Consultancy, Honoraria. Beksac:Celgene: Honoraria, Speakers Bureau; Janssen-Cilag: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Allietta:Covance for Janssen-Cilag: Employment. Broer:Janssen-Cilag: Employment. Couturier:Janssen-Cilag: Employment. Angermund:Janssen-Cilag: Employment. Facon:Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals REFRACTORINESS TO DONOR PLATELETS TRANSFUSION IN PATIENTS WITH APLASTIC ANEMIA AND HEMOBLASTOSIS

2018 ◽  
Vol 13 (2) ◽  
pp. 62-72
Author(s):  
A. F. Rakhmani ◽  
E. A. Mikhaylova ◽  
I. V. Dubinkin ◽  
O. S. Kalmikova ◽  
V. S. Galuzyak ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Solid Phase ◽  
Lymphoblastic Leukemia ◽  
Individual Selection ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Line Of Therapy ◽  
High Degree ◽  
Selection Of

Refractoriness to transfusions of platelet concentrates (PC) adversely affects the conduct of complex therapy in hematological patients. Individual selection of platelets is recommended for such patients. In cases of high degree of alloimmunization with the formation of polyspecific antibodies, when individual selection is difficult, procedures plasmapheresis (PPs) is included in the treatment program.Aims: to evaluate the effectiveness of PC transfusions by individual selection in patients refractory to transfusions and the use of PPs as a second line therapy in combination with individual platelet selection.Materials and methods: from September 2015 to December 2017, 91 patients with refractory to PC transfusions from 1263 patients who received PC transfusion were observed in the center’s clinics. The median age was 43 (18–71) years. M/F – 38/53. Patients: 20 – aplastic anemia (AA), 17 – myelodysplastic syndrome (MDS), 45 – acute myeloid leukemia (AML), 9 – acute lymphoblastic leukemia (ALL). All patients underwent PC transfusion by individual selection (HLA/HPA) Immucor’s Capture-P solid phase technology. In 28 (30 %) of 91 patients, due to the inability to select, there was a need for PP as a second line therapy. Patients: AA – 4 (20 %); MDS – 8 (47 %); AML – 12 (26 %); ALL– 4 (44 %). The median age was 48 (23–71) years. M/F – 8/20. From 2 to 15 procedures were performed (on average – 6) for each patient. All patients received PC transfusions by individual selection by cross-matching immediately after the PP procedure. The efficacy of PC transfusions was assessed by Absolute Platelet Increment (API) and Corrected Count Increment (CCI), relief of hemorrhagic syndrome.Results: in 26 of 28 refractory to PC transfusions patients, in the absence of compatible donor platelets, carrying out PPs in combination with subsequent individual platelet selection promoted relief of hemorrhagic syndrome, increase in API from 3.3 × 109/L at 29.5 × 109/L and CCI from 1.3 to 10.7. Against the background of PPs, combined with individual selection, the degree of alloimmunization (the percentage of incompatible pairs) decreased on average: AA (n = 4) – from 91.7 to 50.2 %; MDS (n = 8) – from 89.6 to 31.6 %; AML (n = 12) – 86.0 to 40.5 % and ALL (n = 4) – from 91.7 to 37.7 %. In 2 patients with a high degree of alloimmunization and after carrying out PPs, it was not possible to select compatible platelets, PC transfusions were ineffective (API = 5 × 109/L, CCI = 1), and hemorrhagic syndrome was not completely managed, but its severity was reduced.Conclusions. With the development of refractoriness to PC transfusions and the ineffectiveness of individual platelet selection, PPs should be used as the second line of therapy, which, combined with individual selection, increases the likelihood of compatible donor-recipient pairs and increases the clinical efficacy of PC transfusions. When PPs is ineffective in combination with individual selection, it is necessary to exclude the syndrome of increased consumption and other mechanisms of refractoriness.

Switch to Subsequent Line of Treatment in Children and Adolescents with Chronic Myeloid Leukemia (CML) Treated with Imatinib: Experience of the International Registry for Chronic Myeloid Leukemia in Children and Adolescents (I-CML-Ped Study)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1576-1576
Author(s):  
Frédéric Millot ◽  
Joelle Guilhot ◽  
Meinolf Suttorp ◽  
Anne Sophie Meunier ◽  
Gunes Adalet Meral ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Children And Adolescents ◽  
Myeloid Leukemia ◽  
Molecular Response ◽  
Second Line ◽  
Front Line ◽  
Second Line Therapy ◽  
Hematologic Response ◽  
International Registry ◽  
Line Therapy

Abstract Aims: To determine in children and adolescents with chronic myeloid leukemia (CML) in chronic phase (CP) treated with imatinib front line, (i) the probability of switch to a second line therapy, (ii) to characterize the reasons and the type of switch and (iii) to determine the impact of the switch on outcome. Methods: Children and adolescents (<18 years) with CML diagnosed later than the year 2000 and enrolled in the international registry for childhood CML (I-CML-Ped Study) were the subjects of the study. Results: The I-CML-Ped study enrolled 301 children and adolescents with CML in CP treated with imatinib front line. Among them 112 patients subsequently switched to a second line therapy (median duration of imatinib treatment before the switch: 16 months [range: 1-111]).The probability of switch at 38 months was 50% (95% CI: 29-60). Primary resistance was the cause of switch in 47% of the patients: failure to achieve complete hematologic response (CHR, 1%), complete cytogenetic response (CCR, 20%) or major molecular response (MMR, 24%); not detailed (2%). A loss of response (CHR loss [2%] or CCR loss [4%] or MMR loss [13%]) or progression were the cause of switch in 19% and 4% of the patients, respectively. Occurrence of non hematologic toxicity (mainly muscle-skeleton pain) was the cause of switch in 10% of the patients. The reason of switch was the physician's choice in 20% of the patients (switch to hematopoietic stem cell transplantation [HSCT] while the patients were in MMR or deeper molecular response). The second line therapy consisted of second generation tyrosine kinase inhibitors (63%), chemotherapy (4%) or HSCT (33%). With a median follow up of 38 months (range: 2-150), overall, 8 deaths were recorded among switching patients: all were patients transplanted for acute phase (4 patients), hematologic resistance (1 patient), loss of hematologic response (1 patient) or physician's choice (2 patients). The causes of death were treatment related mortality (7 patients) and relapse (1 patient). One death only was recorded among the non switching patients. The probability of overall survival at 48 months was 90% (95% CI: 81% - 95%) for switching patients and 98% (95% CI: 89% - 100%) (p=0.005) for the non switching patients. Conclusion: Treatment failure is the main reason for a switch to a second line therapy in children and adolescents treated with imatinib front line. Efficacy of second line therapy still needs improvement. Disclosures No relevant conflicts of interest to declare.

Drug Toxicities in Second-Line Treatment of Chronic Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5173-5173
Author(s):  
Tarcila S Datoguia ◽  
Hugo R C Silva ◽  
Amauri M C R Junior ◽  
José Salvador Oliveira ◽  
Monika Conchon
Keyword(s):  
Side Effects ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Hematological Toxicity ◽  
Molecular Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Cutaneous Rash

Abstract Introduction Chronic myeloid leukemia (CML) is known to be a myeloproliferative neoplasm that involves a genetic abnormality defined as Philadelphia chromosome. Part of chromosome 9 becomes attached to chromosome 22, forming the BCR-ABL fusion gene, which is an oncogenic tyrosine kinase. The rise of the tyrosine kinase inhibitors (TKIs) has transformed the outcome of CML. Imatinib was the first TKI approved for treating patients diagnosed with CML in 2001. Dasatinib and Nilotinib were accredited as second-line therapy in 2006 and 2007, respectively, for patients who had failed previous therapy. Although these new drugs improved response compared with imatinib, they also have important side effects that can lead to non-adherence to treatment. Given the importance to maintain regular treatment to avoid disease progression, this paper aims to discuss the drug toxicities in patients undergoing second-line therapy. Patients and methods This study was an observational analysis using medical records in Santa Marcelina Hospital, a public service located in São Paulo, Brazil. Results A total of 58 CML patients taking second-line therapy were included, 28 with dasatinib and 30 with nilotinib. In dasatinib group, only 3 patients were diagnosed accelerated phase and each one had different side effects, as hematological toxicity, pleural effusion and ulcerative colitis. Of 25 chronic phase patients taking dasatinib, 12 (48%) presented with clinical and laboratorial abnormalities: 3.5% had hematological toxicity (2% with severe bleeding), 4% had cutaneous rash, 10.7% with ulcerative colitis (confirmed in bowel biopsy) and 18% developed pleural effusion. 25% of all dasatinib patient with side effects lost molecular response and started a third TKI. In nilotinib cohort, 7 patients were diagnosed with CML accelerated phase and only two developed liver toxicity. 23 patients were chronic phase and 60% presented with several side effects: 3% hypertriglyceridemia, 6% had hematological toxicity, 6% with dyspepsia, 10% had cutaneous rash and 27% presented with higher liver transaminase. 7% of all nilotinib patients who developed side effects lost molecular response and had to discontinue therapy. Discussion Several examples of side effects can be described with all TKI including cytopenias, fatigue, pain, fluid retention, GI disorders, skin complains, cardiac and liver toxicities but grade 3-4 occurs in less than 2-3% of patients as Jabour et al reported. Despite of important adverse effects, dasatinib and nilotinib induce rapid and durable hematologic and cytogenetic response. In general, the most related toxicities are self-limited and manageable as Kantarjian related. Comparisons between these two second-line therapy using intolerance criteria can be difficult to represent because studies published until now have two different types of population in terms of cytogenetic response achieved previously with imatinib, for example. So, to have a successful treatment, it is important to consider other variables as comorbidities and mutational status as referred Mathisen et al. Individualized risk assessment, between CML and patients characteristics, should influence treatment choices and clinical management. In conclusion, the efficacy and safety of dasatinib and nilotinib have been confirmed by long-term outcome. Clearly these drugs have unique pharmacologic profiles and response patterns in every single patient, but the goal of treating these patients is the correct management of adverse events without losing molecular response. Disclosures No relevant conflicts of interest to declare.

Retreatment Patterns and Outcomes Among Patients with Relapsed Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5935-5935
Author(s):  
Lincy S Lal ◽  
Benjamin J Chastek ◽  
Cori Blauer-Peterson ◽  
Eric M Maiese
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Index Date ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Risk Of Death ◽  
Line Therapy ◽  
Line Of Therapy

Abstract Introduction: Clinical trials have suggested that retreatment with multiple myeloma (MM) therapy provides clinical benefit (Mohty 2012), however, little is known about real-world utilization and outcomes of retreatment. Information from this analysis will help to better understand the real-world impact of retreatment for management of first MM relapse. Methods: A retrospective claims analysis of commercial and Medicare Advantage patients aged 18 years in the Optum Research Database. To be included, patients had to have ≥ 2 medical claims ≥ 30 days apart with an MM diagnoses (ICD-9 =203.00) between 01 Jan 2009 and 31 Dec 2013 (study period); ≥ 2 lines of therapy and no evidence of hematopoietic cell transplant during the study period and data available for 1 year prior to index date and ≥ 6 months post index date. The date of the first claim of an NCCN recommended MM treatment during the study period was considered the index date. All MM treatments identified < 30 days of the index date were considered part of first line of therapy. An algorithm was developed for identifying subsequent lines of therapy. A new line of therapy was identified when there was a switch to a new agent < 180 days of discontinuation of the prior line of therapy or retreatment with the same treatment ≥ 180 days of discontinuation with previously used agents. Additionally, patients had to be treated for relapse MM defined according to lines of therapy when 1) there was an active line of therapy ≥ 60 days long and there was a gap of ≥ 180 days from the end of the line of active therapy to the start of the next line of active therapy or 2) there was a line of therapy ≥ 180 days long and a different treatment was started, with or without a 180-day gap between discontinuation of the prior line and start of the subsequent line of therapy . The data evaluated in the analysis included baseline demographics, Quan-Charlson comorbidity scores, line of therapy, and clinical outcomes, including treatment duration and overall survival. Data were analyzed using chi-square and t-tests to compare patients with retreatment vs. treatment with a different regimen for first relapse MM (i.e. second-line therapy). Results: A total of 252 patients (mean age: 70 yrs; 48% male) were identified as having second-line treatment for relapse MM; 90 patients (35.7%) were retreated with the same regimen and 162 (64.3%) patients were treated with a different regimen. Mean Quan-Charlson comorbidity scores were equal between the two groups (p=0.585). Among the retreatment group, 48.2% were treated with monotherapy for first-line, compared to 25.2% of the different regimen group (p-value < 0.001). Dexamethasone (dex) monotherapy, bortezomib plus dex, and lenalidomide plus dex were common regimens used in retreatment, see Figure 1. Lenalidomide plus dex was also commonly used as a different regimen for second-line treatment. Additionally, dex monotherapy was significantly less likely to be used as a new therapy compared to being used as retreatment for second-line therapy (p<0.05). Conversely, bortezomib plus lenalidomide plus dex was significantly more likely to be used as a new therapy compared to being used as retreatment for second-line treatment (p<0.05). The mean length of relapse line was 161 days in the retreatment group versus 212 days in the different regimen group (p-value 0.067). The incidence rate of death was 13 events (1.43 events per 10,000 person-days of follow-up) in the retreatment group versus 22 events (1.51 events per 10,000) in the different regimen group (p=0.895). Figure 1: Second-line Treatment Regimens among Patients who Received the Same Regimen (Retreatment) vs. a Different Regimen for the Treatment of First-Relapse MM\s Conclusions: In this analysis, approximately one-third of patients were retreated with the same treatments in first-line and second-line of therapy. Patients who were retreated with the same regimen tended to have shorter duration of second-line therapy. However, risk of death did not appear to differ between the two groups. This real-world analysis suggests that retreatment in second-line may affect the time to next treatment, but may not negatively impact the overall risk of death. Reference: Mohty B, El-Cheikh J, Yakoub-Agha I, et al. Treatment strategies in relapsed and refractory multiple myeloma: a focus on drug sequencing and 'retreatment' approaches in the era of novel agents. Leukemia 2012; 26: 73-85. Figure 1 Figure 1. Disclosures Lal: Optum: Employment. Chastek:Optum: Employment. Blauer-Peterson:Optum: Employment. Maiese:Janssen Scientific Affairs, LLC: Employment.

Responses to Dasatinib as a Second- and Third-Line Tyrosine Kinase Inhibitor in Chronic Phase Chronic Myeloid Leukaemia Patients

2019 ◽  
Vol 142 (2) ◽  
pp. 79-86 ◽  
Author(s):  
Jiaqi Tan ◽  
Mengxing Xue ◽  
Jinlan Pan ◽  
Jiannong Cen ◽  
Xiaomei Qi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Chronic Phase ◽  
Molecular Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Dasatinib Treatment

We retrospectively evaluated the efficacy and safety of dasatinib among 48 Chinese patients with chronic phase chronic myeloid leukaemia. The proportions of patients achieving the optimal molecular responses at 3, 6, and 12 months, a major molecular response (MMR) rate and a complete cytogenetic response (CCyR) rate were 87.0, 87.0, 72.2, 45.8, and 72.7% for patients with dasatinib as second-line therapy, and 34.8, 34.8, 33.3, 20.8, and 46.2% as third-line therapy, respectively. A BCR-ABL1 transcript level on the International Scale (BCR-ABL1IS) of ≤10% at the initiation of ­dasatinib treatment was found to be associated with a higher probability of achieving MMR. Among patients with a ­BCR-ABL1IS higher than 10% at initiation of dasatinib treatment, dasatinib showed better performance as a second-line therapy than as a third-line therapy. The patients who achieved an optimal molecular response at 3 months had a superior cumulative incidence of MMR and CCyR compared with patients who failed to achieve such a response. Dasatinib induced considerable responses as a second-line treatment, especially in patients with a BCR-ABL1IS ≤10% at initiation of treatment, whereas the efficacy was limited in patients receiving third-line therapy with a BCR-ABL1IS >10% at the initiation of treatment.

Sign in / Sign up

Export Citation Format

Share Document