Cardiotoxicity and Treatment Efficacy of Not Pegilated Liposomal Doxorubicin in Haematological Malignancies: Our Experience.

Backgrounds. Not pegilated liposomal doxorubicin (Myocet®) has a better pharmacokinetic profile with less myelosuppression, much lower gastroenterological and cardiological toxicity than conventional doxorubicin. In order to reduce toxicity of conventional doxorubicin, in our department from 2002 to 2007 we have treated patients with Multiple Myeloma (MM) and Non-Hodgkin’s Lymphoma (NHL) with therapeutical regimens replacing conventional anthracyclines with not pegilated liposomal doxorubicin.

Methods. In our department, from 2002 to 2007, 35 patients (17M,18F) with a median age of 68.8±9.6(range 82–33) affected by Multiple Myeloma (MM) received one or more cycles according to chemiotherapic scheme: VCR 1mg iv at day 1 + Myocet® 25mg/sm iv at day 2 + CTX 100mg/sm os days 1–4 + PDN 60mg/sm os days 1–4. Diagnosis concerned patients with IgG Myeloma (n=26), IgA Myeloma (n=7), micromolecular Myeloma (n=1) and PL (n=1). 22 patients (16M,6F) with a median age of 63.6±9.6 (range 45–79) affected by NHL received chemoimmunotherapy COMP21-R (CTX, Myocet®, VCR and PDN plus Rituximab). Four patients were stage I, 7 stage II, 6 stage III and 5 stage IV. According to IPI score: 2 patients were low risk, 6 low-intermediate, 8 intermediate-high and 6 high risk. In all patients, chemoimmunotherapy induced cardiologic evaluation was made considering Left Ventricular Ejection Fraction (LVEF): cardiotoxicity was evaluated testing the null hypothesis that the LVEF delta is more negative than −4% of the baseline value before chemotherapy (which was felt to be a reasonable clinical threshold separating non-clinically-significant cardiac toxicity from clinically significant damage due to chemotherapy).

Results. In MM patients evaluation of treatment was made for 31 patients: mean Monoclonal Component (MC) has been reduced from 3048.2±2296.9 to 2353,7±1912.4 and the one sided t-test on the variable delta resulted statistically significant (P = 0.038). Response of treatment was CR 43,3%, PR 23,3%, DP 16,7%, NR 16,7% but no statistically significant correlations were present with both the line of treatment and the diagnosis. For NHL evaluation was made in 20 patients: 17 (77.3%) obtained a Complete Remission (CR), 1 (4.5%) a Partial Remission (PR) and 2 (9.1%) Not Respond (NR) to therapy: no statistically significant correlations were present with both the line of treatment and the diagnosis. In all patients (21 NHL and 30MM, totally 51 subjects), Myocet® cardiotoxicity has been evaluated by LVEF assessment at baseline and monitored along the course of the treatment: baseline mean was 57.8±5.4% and slightly lowered to 55.6±5.2% at the end of treatment. For each sub-population and for the entire population a one-sided t-test was performed in order to determine whether therapy with not pegilated liposomal doxorubicin determines relatively low cardiotoxicity: the tests resulted significant (NHL: P = 0.022, MM: P = 0.0021, All: P = 0.00020), leading to reject the null hypothesis in favour of the alternative hypothesis that cardiotoxicity is actually less severe and that the decrement of LVEF is not as negative as −4%.

Conclusion. Myocet® reduce cardiotoxicity and is effective in the treatment of MM and NHL patients.