Orphan cancers, a new drug available

Good news on the front of orphan neoplasms. Aifa has in fact approved the refundability Of tagraxofusbthe first therapy for blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare blood cancer with a severe prognosis, for which specific drugs were lacking until now. The measure of the drug agency follows the approval of tagraxofusb by the EMA, which took place in 2021, and makes our country the second nation to make the drug available in Europe, after Germany.

The orphan disease

Blastic plasmacytoid dendritic cell neoplasm is a blood cancer characterized by overexpression of the CD123 antigen. The disease usually begins with multiple, infiltrating, dark-coloured skin lesions, and in its course it can affect the bone marrow, central nervous system and lymph nodes, thus becoming a systemic pathology. It has a very low incidence, there are less than one hundred new cases every year in Italy, and it has only recently found an adequate definition, being classified within aggressive myeloid neoplasms.

The clinical management of patients with blast plasmacytoid dendritic cell neoplasm is complicated by the fact that the tumor often reveals a resistence intrinsic to standard chemotherapy, with transient drug responses that do not translate into survival benefits. For this reason, the arrival of a specific drug is hailed by experts as a small revolution, which will allow patients to avoid the serious toxicities that characterize previously used chemotherapy regimens.

“Before tagraxofusp, there were no authorized drugs for this neoplasm and, in clinical practice, intensive chemotherapy regimens were normally used for the treatment of leukemia or lymphoma”, explains Pier Luigi Zinzani, Full Professor of Hematology at the University of Bologna. “Tagraxofusp is a first-in-class, targeted therapy that acts selectively against the CD123 antigen. In the pivotal study involving 89 patients, the drug resulted in an overall response of 75% and remission, complete or with a skin abnormality not indicative of active disease, was 57%. And 51% of patients in remission underwent successful hematopoietic stem cell transplantation, predominantly of the allogeneic type”.

The new drug

Tagraxofuspapproved as first-line monotherapy for patients affected by BPDCN, is therefore able to bring the tumor into remission, allowing in many cases to then resort to a hematopoietic stem cell transplant which gets better further the chances of recovery. “Tagraxofusp can increase the number of patients who achieve remission without experiencing the toxicity of intensive chemotherapy and who, therefore, are candidates for transplantation”, confirms Emanuele Angelucci, Director of the Complex Structure of Hematology and Cellular Therapies of the San Martino Polyclinic Hospital in Genoa . “The drug also showed a favorable risk-benefit profile in ‘real life’, with an efficacy that appears to be even higher than that reported in the pivotal trial”.

The preliminary results of the ‘Expanded Access Program (EAP)’ retrospective study, relating to 22 patients treated with tagraxofusp, 15 of whom on the first line, presented last December at the American Society of Hematology congress, in fact revealed an overall response of 87 % and a complete remission rate of 67%, with 50% of patients then undergoing stem cell transplantation. Data that Angelucci does not hesitate to define as extremely satisfactory, given the aggressiveness of the pathology.