Justin W. Taylor, MD, assistant professor, lab head/PI, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the evolution of frontline treatment options for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), including the integration of tagraxofusp-erzs (SL-401; Elzonris) into the treatment armamentarium in this disease space.

On December 21, 2018, the first-in-class CD123-targeted therapy tagraxofusp gained FDA approval for the treatment of adult and pediatric patients 2 years of age and older with BPDCN.

Prior to this approval, there were no agents specifically approved for the treatment of patients with BPDCN, Taylor begins. Instead, therapeutic approaches utilized in other hematologic malignancies were often applied to BPDCN treatment, he says. This included induction chemotherapy, which is administered in acute myeloid leukemia, or more intensive chemotherapy regimens administered for acute lymphoblastic leukemia, Taylor elaborates. Elderly patients or those who could not tolerate these intensive regimens were treated with a steroid and the antineoplastic agent vincristine, he adds. This regimen is commonly used for treatment in lymphoma.

Several retrospective studies demonstrated that these regimens all provide a median overall survival between 1 and 2 years, indicating the need for better therapeutic options in this disease setting, Taylor notes. The approval of tagraxofusp addressed this unmet need, and provided patients with a unique, targeted approach for BPDCN, he states.

Tagraxofusp consists of the naturally occurring cytokine IL-3, which is linked to a partial diphtheria toxin , Taylor explains. The resulting immunotoxin binds to the IL-3 receptor on CD123-expressing cells with high affinity, and is subsequently brought into the cell through receptor-mediated endocytosis.

The agent’s initial approval was based on efficacy data from the single-arm STML-401-0114 trial (NCT02113982) of patients with BPDCN, Taylor continues. In the pivotal cohort of this trial, patients with treatment-naïve BPDCN receiving tagraxofusp monotherapy had a complete response rate of 53.8%, and median duration of response was not reached at a median follow-up of 11.5 months. An exploratory analysis of the second cohort showed similar response rates for patients with relapsed or refractory BPDCN, supporting the agent’s approval for both patient subsets, Taylor concludes.

Videos

Justin W. Taylor, MD, discusses the evolution of frontline treatment options for patients with blastic plasmacytoid dendritic cell neoplasm, including the integration of tagraxofusp-erzs into the treatment armamentarium in this disease space.

Dr Taylor on the Integration of Tagraxofusp Into the Frontline Treatment Armamentarium for BPDCN

Justin W. Taylor, MD, assistant professor, lab head/ PI, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses findings from a genomic analysis on BTK inhibitors in chronic lymphocytic leukemia (CLL).

This analysis examined a cohort of 55 patients from the phase 1/2 BRUIN study (NCT03740529) treated with pirtobrutinib (LOXO-305), Taylor says. The analysis identified 9 patients in the cohort who had resistance to the therapy, meaning most patients were still responding to pirtobrutinib, Taylor explains. However, further studies will need to be conducted to identify what the resistance in 9 patients might signal, Taylor adds.

Among the 9 patients who developed resistance, 7 of them had them had 

, Taylor continues. The most common mutations were 

, which clustered within the drug binding pocket and prevented pirtobrutinib from binding, Taylor concludes

Justin W. Taylor, MD, discusses findings from a genomic analysis on BTK inhibitors in chronic lymphocytic leukemia. 


Dr. Taylor on Findings from a Genomic Analysis on BTK Inhibitors in CLL

Justin Taylor, MD, attending physician at Memorial Sloan Kettering Cancer Center, discusses the design of an ongoing phase II clinical trial evaluating the combination of frontline vemurafenib (Zelboraf) plus obinutuzumab (Gazyva) in patients with hairy cell leukemia, in an interview during the 

2019 Hairy Cell Leukemia Foundation Annual Conference

The phase II trial had a 2-fold design. Nine patients were treated in the first stage with the vemurafenib combination. Taylor explains they would cut off treatment and end the trial if the responses were not as high as researchers expected, but that didn’t happen. More patients are being enrolled currently to fulfill the second stage of the trial, which has expanded to include 24 patients.

Vemurafenib is administered for a limited duration. Patients received the oral pill twice daily for 4 cycles, which is approximately 4 months of treatment. Obinutuzumab is given as an injection starting in the second cycle. Patients receive obinutuzumab once monthly.

View more from the 2019 Hairy Cell Leukemia Foundation Annual Conference

Justin Taylor, MD, discusses the design of an ongoing phase II clinical trial evaluating the combination of frontline vemurafenib plus obinutuzumab in patients with hairy cell leukemia.

Justin Taylor, MD

Articles

Dr Taylor on the Integration of Tagraxofusp Into the Frontline Treatment Armamentarium for BPDCN

Dr. Taylor on Findings from a Genomic Analysis on BTK Inhibitors in CLL

Dr. Taylor on Ongoing Phase II Trial of Frontline Vemurafenib Combo in Hairy Cell Leukemia