Response to Comment on: “Is it time to reduce the doxorubicin dosage in Hodgkin lymphoma therapy?”

I would like to thank Drs. Picardi and Vincenzi for their interest in the recent editorial entitled “Is it time to reduce the doxorubicin dosage in Hodgkin lymphoma therapy?”, published in Haematologica.¹ In their comment, the authors are asking a different question: “Is it time to increase the liposomal doxorubicin dosage for the frontline therapy in young adults and adults with classic Hodgkin lymphoma?”.² Picardi and Vincenzi suggest using non-pegylated liposomal doxorubicin (Myocet^TM) in a protocol where patients receive Myocet+BVD, with a cumulative doxorubicin dose of 340 mg/m². According to the current guidelines, a doxorubicin dose of ≥250 mg/m² is considered high. With this dose, a subclinical cardiac effect is documented in up to 30% of patients and cardiac dysfunction in approximately 5-9% of patients, increasing to 18% at a doxorubicin dose of 350 mg/m².^3-6 The authors assume that the application of this modified formula (Myocet+BVD), reported to carry reduced acute toxicity, allows for a safe increase in the doxorubicin dose without causing late cardiomyopathy. In their study, 27/28 patients have achieved interim PET negativity and 6 patients have undergone additional radiation therapy, including the mediastinal field in one patient. While there has been no evidence of reduced cardiac function at a 60-month follow-up either in the global longitudinal strain or left ventricular ejection fraction, this follow-up is rather short and cannot be predictive of longer-term toxicity. Since the delayed onset of progressive irreversible heart failure can present even more than 20 years after completing doxorubicin therapy, the safety of the proposed therapeutic approach needs to be further evaluated.

Of note, Myocet^TM is approved only in Europe and for metastatic breast cancer therapy. This drug might be considered for use at a regular dosage at baseline in patients with reduced cardiac function, who cannot tolerate conventional doxorubicin dosage. This issue could be addressed in a phase II study.

Footnotes

• Received March 12, 2026
• Accepted March 15, 2026

Correspondence

E.J. DANN - e_dann@rambam.health.gov.il

Disclosures

No conflicts of interest to disclose.