Why Physicians Recommend Tagraxofusp in BPDCN

What would you recommend for patients with newly diagnosed blastic plasmacytoid dendritic cell neoplasm (BPDCN)?

Thomas W. LeBlanc, MD, MA, MHS

Associate Professor of Medicine

Hematologic Malignancies and Cellular Therapy

Associate Professor in Population Health Sciences

Duke University School of Medicine

Duke Cancer Institute​

Durham, NC

I think best standard of care therapy is tagraxofusp-exrs [Elzonris] upfront, with consolidative allogeneic transplant to follow. Some of these patients will be long-term survivors now, but effectively none of them will be on other therapies and without transplant. Since this is a very rare disease…there are all these different stages of treatment…. Ultimately, what it comes down to now is that the FDA approved [tagraxofusp] at 12 mg/kg given intravenously daily on days 1 through 5 on a 21 day cycle, and then you continue it indefinitely until progression or unacceptable toxicity.¹ [However, the patient] has to have an albumin of 3.2 g/dL or higher to start this drug and they’ll need a decent performance status. Now, we tend to think about it like an induction therapy, and while it's not nearly as toxic as...[other induction therapies], the patient has to have decent organ function and they can't be bed bound, or they probably won't do well with this therapy.

Please describe the baseline characteristics of patients on the phase 1/2 0014 study (NCT02113982).

There were more men than women [on this study], because that's who gets this disease more often.² [The patient population was split evenly] between those with an ECOG performance status of 0 and 1, with a little bit more ECOG scores of 1 for patients with relapsed/refractory disease. Almost everybody had skin involvement, but half to almost two thirds with narrow involvement. All these patients had prior therapies...and these patients who don't have other options that are going to work at all for them. We didn't even have venetoclax [Venclexta] when this study was going on, which has activity in BPDCN and it's a great additional option to have, it's just not usually first line.

What stood out to you from the trial initially?

When you look at the efficacy results for this trial, it's quite impressive. There was an overall response rate [ORR] of 90%, so 9 out of 10 patients getting a response, and the composite complete response [CR] rate is nearly 3 out of 4 patients at 72%.³ [So many patients that]...went on to stem cell transplants...had responses and many had them for quite a significant period of time.... There was near complete resolution of skin lesions [for many of these patients, but you may notice] a little bit of residual hyperpigmentation that I would think of as scarring honestly, it's probably not active disease...but it’s a highly effective therapy due to the ORR and the CR rate. This is why I like to use this as a bridge to transplant, because this is better than anything we've seen historically with conventional cytotoxic therapies.

How have these results held up?

This has been impressive to see these kinds of results.... In different stages of the study, there was a composite CR rate of 57% and ORR of 75% [from stages 1 through 4 of the study with a median follow-up of 34 months], while 32% bridged to transplant and about half bridged to transplant after they got to a CR.² The median duration of the CRs is pretty good, and was at about half of patients 24 months with a good duration of follow-up. The [overall survival probability] at 24 months is 40%,² which was not something we've seen previously with this disease.

^References:

^{1. FDA approves tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm. FDA. December 26, 2018. Accessed May 20, 2024. https://tinyurl.com/2c7rhz2y}

^{2. Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm. N Engl J Med. 2019;380(17):1628-1637. doi:10.1056/NEJMoa1815105}

^{3. Pemmaraju N, Sweet KL, Stein AS, et al. Long-term benefits of tagraxofusp for patients with blastic plasmacytoid dendritic cell neoplasm. J Clin Oncol. 2022;40(26):3032-3036. doi:10.1200/JCO.22.00034}