Adi Shacham-Abulafia1, Pia Raanani1, David Lavie2, Yulia Volchek3, Ron Ram4, Ilana Helman5, Liat Shargian6, Anna Gourevitch7, Evgeni Chubar8, Roy Ratzon9, Uri Rozovski10. 1. Institute of Hematology, Davidoff Cancer Centre, Beilinson Hospital, Rabin Medical Centre, Petah-Tiqva, Israel; Sackler School of Medicine, Tel Aviv University, Ramat-Aviv, Israel. 2. Department of Hematology, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel. 3. Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 4. Sackler School of Medicine, Tel Aviv University, Ramat-Aviv, Israel; Bone Marrow Transplantation Unit, Sourasky Medical Center, Tel Aviv, Israel. 5. Department of Hematology, Meir Medical Center, Kfar Saba, Israel. 6. Institute of Hematology, Davidoff Cancer Centre, Beilinson Hospital, Rabin Medical Centre, Petah-Tiqva, Israel. 7. Hematology Institute, Soroka University Medical Center, Beer-Sheva, Israel. 8. Hematology unit, HaEmek Medical Center, Afula, Israel. 9. Sackler School of Medicine, Tel Aviv University, Ramat-Aviv, Israel; Geha Mental Health Center, Psychiatric Hospital, Petah-Tiqva, Israel. 10. Institute of Hematology, Davidoff Cancer Centre, Beilinson Hospital, Rabin Medical Centre, Petah-Tiqva, Israel; Sackler School of Medicine, Tel Aviv University, Ramat-Aviv, Israel. Electronic address: rozovski.uri@gmail.com.
Abstract
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase. Only 9 patients (26%) harbored the T315I (threonine to isoleucine mutation at position 315) mutation. All patients had received ≥ 1 previous tyrosine kinase inhibitor. The median age in our cohort was 43 years (range, 9-82 years), significantly younger than expected for patients with relapsed or refractory CML and 20 years younger than the median age of patients who participated in the PACE (ponatinib Philadelphia-positive acute lymphoblastic leukemia and CML evaluation) trial. During a median follow-up of 14 months (range, 1-51 months), the overall response rate was 85%. Of 34 patients, 16 (47%) experienced at least a major molecular response. Of the 37 total patients, another 16 patients (43%) discontinued treatment because of disease progression (n = 6), vascular complications (n = 1), severe cytopenia (n = 2), or for other reasons (n = 7). CONCLUSION: In real life, ponatinib is a "niche-drug" reserved for a unique population of exceptionally young patients with CML with or without the T315I mutation. In this highly selected group, very different from the PACE cohort, ponatinib achieved high overall response rates.
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase. Only 9 patients (26%) harbored the T315I (threonine to isoleucine mutation at position 315) mutation. All patients had received ≥ 1 previous tyrosine kinase inhibitor. The median age in our cohort was 43 years (range, 9-82 years), significantly younger than expected for patients with relapsed or refractory CML and 20 years younger than the median age of patients who participated in the PACE (ponatinibPhiladelphia-positive acute lymphoblastic leukemia and CML evaluation) trial. During a median follow-up of 14 months (range, 1-51 months), the overall response rate was 85%. Of 34 patients, 16 (47%) experienced at least a major molecular response. Of the 37 total patients, another 16 patients (43%) discontinued treatment because of disease progression (n = 6), vascular complications (n = 1), severe cytopenia (n = 2), or for other reasons (n = 7). CONCLUSION: In real life, ponatinib is a "niche-drug" reserved for a unique population of exceptionally young patients with CML with or without the T315I mutation. In this highly selected group, very different from the PACE cohort, ponatinib achieved high overall response rates.