Contributions
Abstract: PB1778
Type: Publication Only
Background
Anthracyclines are essential in the treatment of aggressive B cell Non Hodgkin Lymphoma (NHL). Nevertheless, in clinical practice the substantial risk of developing drug induced cardiotoxicity, in particular congestive heart failure (CHF), results often in ommission of anthracyclines in first line treatment of this otherwise curable malignant lymphomas in patients at risk. Known cofactors for developing anthracycline induced CHF are cumulative anthracycline dose, female sex, age > 65, diabetes, impaired cardiac function, and hypertension. No standard treatment for patients with aggressive B cell NHL having one of this cofactors exist. Pixantrone is an aza-anthracenedione showing reduced cardiotoxicity in vitro compared to standard anthracyclines. Recent data by Herbrecht et al. (Ann Oncol, 2013, 24:2618) showed that first line combined rituximab based immunochemotherapy treatment for DLBCL with the R-CPOP protocol (derived from R-CHOP in which doxorubicin is substituted with pixantrone 88 mg/m2) resulted in similar PFS when compared with R-CHOP, while reduced grade 3 CHF rates could be observed.
Aims
We wanted to explore the feasibility of R-CPOP treatment in aggressive B cell NHL patients with cofactors for developing anthracycline induced CHF.
Methods
In an unicenter setting we started in 2015 to use this protocol (6 cycles CPOP, 8x rituximab, every three weeks) in ten patients. Diagnoses included DLBCL (8 pat.), Richter transformation and high grade B cell lymphoma (1 pat. each). Median age was 72,4 years (range: 61-84) with an IPI 3-5 in 70% of patients. The main cardiac risk factor in all patients was known clinical CHF with a median left ventricular ejection fraction (LVEF) of 37% (range: 25-55). Known causes were ischemic heart disease in 5 patients. Three patients had exposure to anthracyclines in prior cancer treatment.
Results
Eight patients received four to six cycles of R-CPOP. Among those, treatment was well tolerated with hematological toxocities as expected in this patient cohort and no deaths due to neutropenic complications. No one experienced higher grade acute cardiac toxicity during treatment. Two patients did not complete the treatment, one with an initial LVEF of 25% experienced a deterioration of the CHF after the first cycle, the other with Richter transformation showed an early disease progress. While treatment is still ongoing, all of the remaining patients responded to R-CPOP with confirmed complete remission in 5 (62%) patients. This results in a median overall survival of 10 months (range: 2-31 months) so far.
Conclusion
In conclusion, using pixantrone in a first line combined R-CPOP treatment protocol for aggressive B cell NHL is feasible. An ongoing study (DRKS-ID: DRKS00000718) is active in recruiting patients and will further explore duration of response and incidence of longterm toxicity of this approach.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): Anthracycline, DLBCL, Pixantrone
Abstract: PB1778
Type: Publication Only
Background
Anthracyclines are essential in the treatment of aggressive B cell Non Hodgkin Lymphoma (NHL). Nevertheless, in clinical practice the substantial risk of developing drug induced cardiotoxicity, in particular congestive heart failure (CHF), results often in ommission of anthracyclines in first line treatment of this otherwise curable malignant lymphomas in patients at risk. Known cofactors for developing anthracycline induced CHF are cumulative anthracycline dose, female sex, age > 65, diabetes, impaired cardiac function, and hypertension. No standard treatment for patients with aggressive B cell NHL having one of this cofactors exist. Pixantrone is an aza-anthracenedione showing reduced cardiotoxicity in vitro compared to standard anthracyclines. Recent data by Herbrecht et al. (Ann Oncol, 2013, 24:2618) showed that first line combined rituximab based immunochemotherapy treatment for DLBCL with the R-CPOP protocol (derived from R-CHOP in which doxorubicin is substituted with pixantrone 88 mg/m2) resulted in similar PFS when compared with R-CHOP, while reduced grade 3 CHF rates could be observed.
Aims
We wanted to explore the feasibility of R-CPOP treatment in aggressive B cell NHL patients with cofactors for developing anthracycline induced CHF.
Methods
In an unicenter setting we started in 2015 to use this protocol (6 cycles CPOP, 8x rituximab, every three weeks) in ten patients. Diagnoses included DLBCL (8 pat.), Richter transformation and high grade B cell lymphoma (1 pat. each). Median age was 72,4 years (range: 61-84) with an IPI 3-5 in 70% of patients. The main cardiac risk factor in all patients was known clinical CHF with a median left ventricular ejection fraction (LVEF) of 37% (range: 25-55). Known causes were ischemic heart disease in 5 patients. Three patients had exposure to anthracyclines in prior cancer treatment.
Results
Eight patients received four to six cycles of R-CPOP. Among those, treatment was well tolerated with hematological toxocities as expected in this patient cohort and no deaths due to neutropenic complications. No one experienced higher grade acute cardiac toxicity during treatment. Two patients did not complete the treatment, one with an initial LVEF of 25% experienced a deterioration of the CHF after the first cycle, the other with Richter transformation showed an early disease progress. While treatment is still ongoing, all of the remaining patients responded to R-CPOP with confirmed complete remission in 5 (62%) patients. This results in a median overall survival of 10 months (range: 2-31 months) so far.
Conclusion
In conclusion, using pixantrone in a first line combined R-CPOP treatment protocol for aggressive B cell NHL is feasible. An ongoing study (DRKS-ID: DRKS00000718) is active in recruiting patients and will further explore duration of response and incidence of longterm toxicity of this approach.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): Anthracycline, DLBCL, Pixantrone