Neil E Kay1, Betsy R LaPlant2, Adam M Pettinger2, Timothy G Call1, Jose F Leis3, Wei Ding1, Sameer A Parikh1, Michael J Conte1, Deborah A Bowen1, Tait D Shanafelt4. 1. a Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA. 2. b Division of Biomedical Statistics and Informatics, Department of Health Sciences Research , Mayo Clinic , Rochester , MN , USA. 3. c Department of Hematology and Oncology , Mayo Clinic , Phoenix , AZ , USA. 4. d Division of Hematology , Stanford University School of Medicine , Stanford , CA , USA.
Abstract
BACKGROUND: 7 regimens of pentostatin based chemoimmunotherapy (CIT) for progressive previously untreated CLL primarily with long term follow-up to update both efficacy and toxicity. RESEARCH DESIGN AND METHODS: Prognostic markers including assessment of IGVH and FISH status were done on all. Response rates and 95% binomial confidence intervals were calculated for each regimen and in the combined cohort. Overall survival and treatment-free survival were evaluated using Kaplan-Meier methods. RESULTS: The initial CIT trial was pentostatin (2 mgs/m2), cyclophosphamide (600 mg/m2) and rituximab (PCR) but subsequent P based CIT trials with modifications in subsequent trials. The cohort (n = 288) included 52% with unmutated IGVH status and del17p (4.5%) and del11q (14.9%). Toxicity profiles were primarily hematologic and no patient has developed MDS or AML after a median follow-up of 6.4 years. The overall response rate across all trials was found to be over 90% with a 41% complete response rate. We validated that the CLL IPI model segregates progressive CLL patients into 4 risk groups associated with OS and TFS. CONCLUSIONS: The high overall and complete response levels in favorable genetic risk CLL along with favorable toxicity profiles provide rationale for consideration of a PC based strategy for previously untreated progressive CLL.
BACKGROUND: 7 regimens of pentostatin based chemoimmunotherapy (CIT) for progressive previously untreated CLL primarily with long term follow-up to update both efficacy and toxicity. RESEARCH DESIGN AND METHODS: Prognostic markers including assessment of IGVH and FISH status were done on all. Response rates and 95% binomial confidence intervals were calculated for each regimen and in the combined cohort. Overall survival and treatment-free survival were evaluated using Kaplan-Meier methods. RESULTS: The initial CIT trial was pentostatin (2 mgs/m2), cyclophosphamide (600 mg/m2) and rituximab (PCR) but subsequent P based CIT trials with modifications in subsequent trials. The cohort (n = 288) included 52% with unmutated IGVH status and del17p (4.5%) and del11q (14.9%). Toxicity profiles were primarily hematologic and no patient has developed MDS or AML after a median follow-up of 6.4 years. The overall response rate across all trials was found to be over 90% with a 41% complete response rate. We validated that the CLL IPI model segregates progressive CLL patients into 4 risk groups associated with OS and TFS. CONCLUSIONS: The high overall and complete response levels in favorable genetic risk CLL along with favorable toxicity profiles provide rationale for consideration of a PC based strategy for previously untreated progressive CLL.
Authors: Sanford Kempin; Zhuoxin Sun; Neil E Kay; Elisabeth M Paietta; Joseph J Mazza; Rhett P Ketterling; Olga Frankfurt; David F Claxton; Joel N Saltzman; Gordan Srkalovic; Natalie S Callander; Gerald Gross; Martin S Tallman Journal: Acta Haematol Date: 2019-07-23 Impact factor: 2.195
Authors: Nina Kreuzberger; Johanna Aag Damen; Marialena Trivella; Lise J Estcourt; Angela Aldin; Lisa Umlauff; Maria Dla Vazquez-Montes; Robert Wolff; Karel Gm Moons; Ina Monsef; Farid Foroutan; Karl-Anton Kreuzer; Nicole Skoetz Journal: Cochrane Database Syst Rev Date: 2020-07-31