Poor efficacy and tolerability of R-CHOP in relapsed/refractory chronic lymphocytic leukemia and Richter transformation

Petra Langerbeins; Raymonde Busch; Nadine Anheier; Jan Dürig; Manuela Bergmann; Maria-Elisabeth Goebeler; Hans-Jürgen Hurtz; Martina B Stauch; Stephan Stilgenbauer; Hartmut Döhner; Anna-Maria Fink; Paula Cramer; Kirsten Fischer; Clemens-Martin Wendtner; Michael Hallek; Barbara Eichhorst

doi:10.1002/ajh.23841

Poor efficacy and tolerability of R-CHOP in relapsed/refractory chronic lymphocytic leukemia and Richter transformation

Am J Hematol. 2014 Dec;89(12):E239-43. doi: 10.1002/ajh.23841. Epub 2014 Sep 26.

Authors

Petra Langerbeins¹, Raymonde Busch, Nadine Anheier, Jan Dürig, Manuela Bergmann, Maria-Elisabeth Goebeler, Hans-Jürgen Hurtz, Martina B Stauch, Stephan Stilgenbauer, Hartmut Döhner, Anna-Maria Fink, Paula Cramer, Kirsten Fischer, Clemens-Martin Wendtner, Michael Hallek, Barbara Eichhorst

Affiliation

¹ Department I of Internal Medicine, Center of Integrated Oncology (CIO), and CECAD-Cluster of Excellence "Cellular Stress Responses in Aging-Associated Diseases," University of Cologne, Germany.

PMID: 25196783
DOI: 10.1002/ajh.23841

Abstract

This phase II trial evaluated efficacy and tolerability of R-CHOP for up to 8 courses in Richter transformation (RT) and up to 6 courses in CLL plus autoimmune cytopenia (AIC) or high-risk (HR) features. HR was defined as fludarabine-refractoriness or early relapse (<36 months) after fludarabine-based treatment; 26 patients were included as HR, 19 patients had AIC, and 15 patients had RT. In the HR cohort, overall response rate was 54%, progression-free and overall survival were 9 and 21 months. In AIC patients overall response rate was 74%, progression-free and overall-survival were 10 and 41 months, respectively, and median increase in hemoglobin was 3.4 g/L. RT patients responded in 67%, progression-free was 10 and overall survival 21 months. The most common adverse events were hematologic toxicities in 92%. Severe infections occurred in 28%. Treatment was discontinued early in 45% of all patients mainly as a result of toxicity. This trial shows that R-CHOP has no role in treating complicated CLL. R-CHOP is associated with significant toxicities and fairly low efficacy compared with almost every other CLL-regimen. In RT, it might still be used as an induction therapy before allogeneic stem cell transplantation.

Trial registration: ClinicalTrials.gov NCT00309881.

Publication types

Clinical Trial, Phase II

MeSH terms

Adult
Aged
Antibodies, Monoclonal, Murine-Derived / administration & dosage
Antibodies, Monoclonal, Murine-Derived / adverse effects
Antineoplastic Combined Chemotherapy Protocols / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / adverse effects*
Cyclophosphamide / administration & dosage
Cyclophosphamide / adverse effects
Doxorubicin / administration & dosage
Doxorubicin / adverse effects
Drug Administration Schedule
Drug Resistance, Neoplasm
Female
Hemoglobins / metabolism
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / complications
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
Leukemia, Lymphocytic, Chronic, B-Cell / mortality
Leukemia, Lymphocytic, Chronic, B-Cell / pathology
Male
Middle Aged
Prednisone / administration & dosage
Prednisone / adverse effects
Purpura, Thrombocytopenic, Idiopathic / complications
Purpura, Thrombocytopenic, Idiopathic / drug therapy*
Purpura, Thrombocytopenic, Idiopathic / mortality
Purpura, Thrombocytopenic, Idiopathic / pathology
Recurrence
Rituximab
Survival Analysis
Treatment Failure
Vidarabine / analogs & derivatives
Vidarabine / therapeutic use
Vincristine / administration & dosage
Vincristine / adverse effects

Substances

Antibodies, Monoclonal, Murine-Derived
Hemoglobins
R-CHOP protocol
Rituximab
Vincristine
Doxorubicin
Cyclophosphamide
Vidarabine
fludarabine
Prednisone

Associated data

ClinicalTrials.gov/NCT00309881