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Association between Proteomic Profile and Molecular Response (MR) in Chronic Myeloid Leukemia (CML) Patients
Abstracts Table Estimated OS in CP-CML patients receiving 3L treatment other than ponatinib OS Time (Years)
Patients
Probability (95% CI)
Arms
0
268
5
100% (– , –)
1 2
229 179
5 5
89% (86%, 93%) 76% (71%, 82%)
3 4
104 15
3 1
64% (58%, 71%) 64% (56%, 71%)
Outcomes Measures: Landmark and median survival were extracted from study reports. Pseudo-individual patient data (IPD) for survival outcomes were derived from digitized Kaplan-Meier (KM) survival curves then pooled and analyzed using KM methods. Pooled results were compared with results for patients receiving ponatinib as 3L treatment in PACE. Results: Thirteen studies (549 patients) were identified that reported median, landmark, or KM curves for survival outcomes for CP-CML patients receiving 3L treatment other than ponatinib. KM curves for OS were obtained for 5 arms (3 nilotinib and/or dasatinib; 2 other TKIs). One study was excluded because the number of patients receiving 3L treatment was small (<10%). OS at 1, 2, 3, and 4 years based on the pooled IPD of non-ponatinib studies is reported in the Table. Conclusions: Estimated OS in patients with CP-CML receiving 3L treatment other than ponatinib appears to be shorter than that observed among patients receiving ponatinib as 3L treatment in PACE: 4-year survival probability among patients receiving 3L ponatinib in PACE is higher than estimated 2-year survival probability in trials of other therapies. Funded by ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
evaluate a possible correlation between depth of MR and proteomicprofile of CML patients, and if possible, to find novel biomarkers complementary to currently existing proven tools to monitor therapy response. Design: 30 serum samples from peripheral blood, were obtained from 30 CML patients observed, between January and December 2014 at the Hematology Unit of “Istituto Tumori Giovanni Paolo II” in Bari, Italy. The proteomic profile was investigated by SELDI ToF Mass Spectrometry platform. Patients or Other Participants: 30 patients (M/F: 12/18) with a median age of 61.5 years (range 27-85) were enrolled in the study. All patients, except one at diagnosis, were in CHR and under treatment with TKIs (9 imatinib, 11 dasatinib, 8 nilotinib, 1 ponatinib) at sample’s collection. 30 samples were obtained from 30 healthy subjects (HS). Results: Comparing sera from patients with different MR [MR1 (including the patient at diagnosis)-MR2-MR3-MR4], statistical analysis found 2 features at 11092Da and 5075Da as differentially expressed and statistically significant (P-value¼0.0034 and 0.0084 respectively) between MR1 and MR4. In particular the peptide at 11092Da was over expressed in MR4 patients. Also the peak at 5075Da was highlighted as statistically significant, but its significance was less important than that of 11092Da due to a slightly worse sensitivity (80%). HS group did not exhibit the over expression of such peptides. Finally, with the aim to give a preliminary identity to the most differentially expressed peak (11092Da), we matched our data with Mascot library available at www.matrixscience.com. The bioinformatic tool identified the peptide with a high probability score, as a part of a nuclear protein ZMIZ2. It would interact with the Wnt/b-catenin pathway participating in its activation. Conclusions: We can try to hypothesize that, in the serum of responsive patients, a part of ZMIZ2 is present, as a consequence of the degradation of the entire protein; this finding results in an under-regulation of the Wnt/b-catenin pathway with consequently a better response.
CML-127
CML-138
Association between Proteomic Profile and Molecular Response (MR) in Chronic Myeloid Leukemia (CML) Patients
Five-Year Efficacy and Safety of Dasatinib and Imatinib by Baseline Comorbidity and Age in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) from DASISION
Nicola Sgherza ,1 Vito Michele Garrisi,2 Massimo Breccia,3 Angela Iacobazzi,4 Nicola Cascavilla,1 Ines Abbate,2 Attilio Guarini4 “Casa Sollievo della Sofferenza” Hospital, Hematology and Stem Cell
1
Transplantation Unit, San Giovanni Rotondo, Italy; 2National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Clinical and 3
Michael J. Mauro ,1 Jorge E. Cortes,2 Andreas Hochhaus,3 Neil P. Shah,4 Ehab L. Atallah,5 Mena Abaskharoun,6 Oumar Sy,6 Giuseppe Saglio7 1
Memorial Sloan Kettering Cancer Center, New York, United States;
2
Experimental Pathology Laboratory, Bari, Italy; Department of Cellular Biotechnologies and Hematology, Sapienza University, Roma,
University of Texas MD Anderson Cancer Center, Houston, United States; 3Universitätsklinikum Jena, Jena, Germany; 4University of
Italy; 4National Cancer Research Centre Istituto Tumori “Giovanni
California San Francisco School of Medicine, San Francisco, United
Paolo II”, Hematology Unit, Bari, Italy
States; 5Froedtert & the Medical College of Wisconsin, Milwaukee, United States; 6Bristol-Myers Squibb, Princeton, United States;
Context: Recent advances in mass spectrometry have allowed the investigation of proteomic modifications associated with solid tumors, hematological neoplasms and identification of therapyerelated proteomes. Objective: The aims of our pilot study were to
S312
-
Clinical Lymphoma, Myeloma & Leukemia September 2017
7
University of Turin, Turin, Italy
Context: Comorbidities in patients with CML may influence treatment-related decisions and impact response and survival.
Patients
Probability (95% CI)
Arms
0
268
5
100% (– , –)
1 2
229 179
5 5
89% (86%, 93%) 76% (71%, 82%)
3 4
104 15
3 1
64% (58%, 71%) 64% (56%, 71%)
Outcomes Measures: Landmark and median survival were extracted from study reports. Pseudo-individual patient data (IPD) for survival outcomes were derived from digitized Kaplan-Meier (KM) survival curves then pooled and analyzed using KM methods. Pooled results were compared with results for patients receiving ponatinib as 3L treatment in PACE. Results: Thirteen studies (549 patients) were identified that reported median, landmark, or KM curves for survival outcomes for CP-CML patients receiving 3L treatment other than ponatinib. KM curves for OS were obtained for 5 arms (3 nilotinib and/or dasatinib; 2 other TKIs). One study was excluded because the number of patients receiving 3L treatment was small (<10%). OS at 1, 2, 3, and 4 years based on the pooled IPD of non-ponatinib studies is reported in the Table. Conclusions: Estimated OS in patients with CP-CML receiving 3L treatment other than ponatinib appears to be shorter than that observed among patients receiving ponatinib as 3L treatment in PACE: 4-year survival probability among patients receiving 3L ponatinib in PACE is higher than estimated 2-year survival probability in trials of other therapies. Funded by ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
evaluate a possible correlation between depth of MR and proteomicprofile of CML patients, and if possible, to find novel biomarkers complementary to currently existing proven tools to monitor therapy response. Design: 30 serum samples from peripheral blood, were obtained from 30 CML patients observed, between January and December 2014 at the Hematology Unit of “Istituto Tumori Giovanni Paolo II” in Bari, Italy. The proteomic profile was investigated by SELDI ToF Mass Spectrometry platform. Patients or Other Participants: 30 patients (M/F: 12/18) with a median age of 61.5 years (range 27-85) were enrolled in the study. All patients, except one at diagnosis, were in CHR and under treatment with TKIs (9 imatinib, 11 dasatinib, 8 nilotinib, 1 ponatinib) at sample’s collection. 30 samples were obtained from 30 healthy subjects (HS). Results: Comparing sera from patients with different MR [MR1 (including the patient at diagnosis)-MR2-MR3-MR4], statistical analysis found 2 features at 11092Da and 5075Da as differentially expressed and statistically significant (P-value¼0.0034 and 0.0084 respectively) between MR1 and MR4. In particular the peptide at 11092Da was over expressed in MR4 patients. Also the peak at 5075Da was highlighted as statistically significant, but its significance was less important than that of 11092Da due to a slightly worse sensitivity (80%). HS group did not exhibit the over expression of such peptides. Finally, with the aim to give a preliminary identity to the most differentially expressed peak (11092Da), we matched our data with Mascot library available at www.matrixscience.com. The bioinformatic tool identified the peptide with a high probability score, as a part of a nuclear protein ZMIZ2. It would interact with the Wnt/b-catenin pathway participating in its activation. Conclusions: We can try to hypothesize that, in the serum of responsive patients, a part of ZMIZ2 is present, as a consequence of the degradation of the entire protein; this finding results in an under-regulation of the Wnt/b-catenin pathway with consequently a better response.
CML-127
CML-138
Association between Proteomic Profile and Molecular Response (MR) in Chronic Myeloid Leukemia (CML) Patients
Five-Year Efficacy and Safety of Dasatinib and Imatinib by Baseline Comorbidity and Age in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) from DASISION
Nicola Sgherza ,1 Vito Michele Garrisi,2 Massimo Breccia,3 Angela Iacobazzi,4 Nicola Cascavilla,1 Ines Abbate,2 Attilio Guarini4 “Casa Sollievo della Sofferenza” Hospital, Hematology and Stem Cell
1
Transplantation Unit, San Giovanni Rotondo, Italy; 2National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Clinical and 3
Michael J. Mauro ,1 Jorge E. Cortes,2 Andreas Hochhaus,3 Neil P. Shah,4 Ehab L. Atallah,5 Mena Abaskharoun,6 Oumar Sy,6 Giuseppe Saglio7 1
Memorial Sloan Kettering Cancer Center, New York, United States;
2
Experimental Pathology Laboratory, Bari, Italy; Department of Cellular Biotechnologies and Hematology, Sapienza University, Roma,
University of Texas MD Anderson Cancer Center, Houston, United States; 3Universitätsklinikum Jena, Jena, Germany; 4University of
Italy; 4National Cancer Research Centre Istituto Tumori “Giovanni
California San Francisco School of Medicine, San Francisco, United
Paolo II”, Hematology Unit, Bari, Italy
States; 5Froedtert & the Medical College of Wisconsin, Milwaukee, United States; 6Bristol-Myers Squibb, Princeton, United States;
Context: Recent advances in mass spectrometry have allowed the investigation of proteomic modifications associated with solid tumors, hematological neoplasms and identification of therapyerelated proteomes. Objective: The aims of our pilot study were to
S312
-
Clinical Lymphoma, Myeloma & Leukemia September 2017
7
University of Turin, Turin, Italy
Context: Comorbidities in patients with CML may influence treatment-related decisions and impact response and survival.