Carraway Explores Use of Tagraxofusp and Allogeneic SCT for BPDCN

Peers & Perspectives in OncologyOctober II 2023
Volume 1
Issue 7
Pages: 30

Hetty Carraway, MD, MBA, discusses treatment with tagraxofusp and allogeneic stem cell transplant for patients with blastic plasmacytoid dendritic cell neoplasm.

Case Summary:

  • A man aged 67 years was referred from a dermatologist.
    • The patient was referred initially to the dermatologist for progressive, persistent, cutaneous nodules that he first noticed 3 weeks prior.
  • Fatigue, 5-kg weight loss over 3 months
  • Medical history: sinusitis, no major comorbidities
  • Physical examination notable for multiple purpuric nodules (measuring ≤ 5 cm on arms, legs, and torso), with no palpable adenopathy or hepatosplenomegaly
  • ECOG performance status: 1
  • Laboratory results: white blood cell count, 14.1 × 103/μL; hemoglobin level, 8.9 g/dL; platelet count, 54 × 103/μL
  • Differential blood count revealing 12% blasts, 32% neutrophils, 16% monocytes, 40% lymphocytes
  • Skin: purpuric nodule • Peripheral blood smear: blastic cells with large and round or slightly irregular nuclei, blast cytoplasm stained grayish blue without granules or Auer rods
  • Bone marrow biopsy result showing 40% blasts by morphology and 80% cellular marrow with interstitial infiltrate
  • Immunohistochemistry of neoplastic cells: CD4, CD56, CD123, and TCL1 positive
  • Flow cytometry: CD4, CD56, CD123; negative for CD34 and T- and B-cell lineage-specific markers
  • Cytogenetics: 46, XY
  • Lumbar puncture not indicative of central nervous system involvement
  • The patient received an ultimate diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) based on clinical and histopathologic findings.
  • The patient received tagraxofusp-erzs (Elzonris) 12 μg/kg per package label for frontline therapy and achieved a complete response (CR) after 1 cycle of therapy.

Q: What were the baseline characteristics of patients treated with 12 μg/kg, once-daily tagraxofusp for BPDCN?

CARRAWAY: The phase 1/2 study [NCT02113982] of [tagraxofusp] enrolled 65 first-line [patients] and 19 patients with relapsed/refractory BPDCN. [Approximately] 80% of the patients were male, and 20% were female. We would have expected a 3:1 ratio, but not surprisingly, there was a difference in the male to female ratio. Predominantly White patients were enrolled. The median age at diagnosis is consistent with what we know, 68 years, and per the protocol criteria, many patients had an ECOG performance status of less than or equal to 1.

Most patients, whether they were in the first line or relapsed/refractory setting, had skin involvement, and 49% [in the first line] and 63% [with prior treatment] had bone marrow involvement. Visceral involvement was 14% in the first line and 21% in [the] relapsed/refractory setting. In the relapsed/ refractory setting, patients had received at least 1 therapy 58% of the time and 2 or 3 therapies 16% and 11% of the time, respectively.1,2

 Duration of Complete Response With Tagraxofusp in Phase 1/2 Trial2

Q: What were the efficacy and safety shown in findings from this trial? The overall response rate for BPDCN [in the trial’s] stages 1 to 3, stage 4, or combined were 90%, 64%, and 75%, respectively. The overall CR plus CRc, [which was CR with residual skin abnormality not indicative of disease], rate was 57%. Thirty-two percent of patients bridged to [allogeneic or autologous stem cell transplant (SCT)], and 51% of patients were bridged to SCT after CR plus CRc. The overall median duration of CR plus CRc was 24.9 months, but it was not reached for patients with stage I to III disease. The duration of response seems to be very promising, particularly in comparison with the outcomes of patients with BPDCN [Table2]. This was exciting, and it led to the FDA approval of tagraxofusp for patients with BPDCN. The median overall survival [OS] was 8.2 months, with a median follow-up of 33.5 months.2,3

For the adverse events [AEs], some patients had elevations in their liver function test [LFT] results, such as AST [aspartate aminotransferase] and ALT [alanine transaminase] 60% to 64% of the time. Patients had issues with peripheral edema [at a rate of] 42%, fatigue at 44%, and fever at 44%. AEs leading to discontinuation or dose interruption were predominantly related to LFT issues, peripheral edema, weight increase, and hypoalbuminemia, which is a concern for capillary leak syndrome [CLS]. For grade 3 or greater treatment-related AEs, thrombocytopenia was in 33% of patients and ALT or AST increase was in 32% and 30% of patients, respectively.2

Q: What is the risk of CLS following tagraxofusp use?

The overall incidence of CLS in clinical trials of tagraxofusp was approximately 55%, and most of it resolved and was at the grade 1 to 2 level. About 6% of patients had grade 3 CLS, and 1% of patients had grade 4 CLS. Two fatal events followed CLS. The common signs and symptoms associated with CLS include hypoalbuminemia, edema, weight gain, and hypotension.4

Q: How do you prevent and manage CLS?

All patients must have a baseline serum albumin [level] of 3.2 g/dL or higher before starting tagraxofusp. During treatment, it is recommended to replace the serum albumin if [the level] is less than 3.5 g/dL or if there is a reduction of 0.5 g/dL or more from baseline. Before each dose of tagraxofusp, check the serum albumin levels.

Patients may need administration of albumin, and they may not be getting it perfectly at day 1, day 2, day 3, day 4, day 5. It can be that you need to interrupt [treatment] to fix the albumin [level] or have some of the toxicities resolve for patients. This is important because CLS can be life threatening and fatal, so it is important to pay attention. The first cycle of this agent should be administered in the inpatient setting, and you want to monitor toxicity during and after the drug administration.4

Typically, after the fifth day…[if] you administered all 5 doses, you want to keep that patient until day 6 and monitor them for at least 24 hours after the completion of the first cycle. For many patients, we premedicate them with a histamine antagonist as well as acetaminophen and steroids prior to each infusion.4

We follow LFTs, kidney function, albumin [level], and vital signs for all patients. Working together with the nursing team is essential. CLS prevention and supportive management focus on making sure before you administer the agent that the patient has adequate cardiac function and adequate serum albumin [level]. Monitor serum albumin levels during treatment and do dose modifications [if necessary].4


• The patient continued tagraxofusp with maintenance of CR for 12 months, with an ECOG performance status score of 1.

• His family inquired about additional options for maintaining remission in the long term.

Q: What is the role of SCT for a patient such as this who is in remission?

[Findings from] studies suggest that being in first remission during receipt of the allogeneic SCT significantly enhances the median OS. Reduced intensity conditioning may be considered in patients who achieve CR but cannot tolerate myeloablative transplant. BPDCN is a rare entity, so we are not going to have huge numbers of patients. For the long-term results and outcomes of patients with CR plus CRc plus or minus SCT with a median follow-up of 34 months, the median OS was 38.4 months, the 24-month OS rate was 66%, and the remission of 12 or more months post-transplant was 72%. [These are] good data…unmatched to anything we know. Even with multiagent chemotherapy, we are still not in a place where we have consistent data [such as] these. In the CR plus CRc group, 4 of 18 patients had prolonged duration of remission and in 2 of the 4 responses, one lasted 27 months and the other lasted 52 months.5

[There were] small numbers of patients after allogeneic SCT; 17 patients were reported. The median age was 39, so [this was] a younger population in general. Again, 80% of this group of 17 patients were male. Some of these patients received therapy other than tagraxofusp. So 11 patients received a hyper-CVAD [cyclophosphamide (Cytoxan), vincristine (Oncovin), doxorubicin (Adriamycin), dexamethasone]–based approach, 6 received tagraxofusp, and 2 received a prior autologous SCT. Four patients ended up moving toward SCT, and only 10 patients were in complete remission.6 So [we have] limited data, but [they are] the best that we can do in terms of generating some of these data points because it is a rare disease entity. Collating these data can be quite important.


• After consultation with the transplant team, the patient declined allogeneic hematopoietic SCT.

• Twenty-two months after starting tagraxofusp, relapse was documented, with recurrence of skin lesions and evolving pancytopenia.

• ECOG performance status: 1

Q: What data provide a guide on what to do after patients have experienced progression?

The North American BPDCN Consortium has put together an overview of the outcomes with different therapies for BPDCN, with a focus on posttransplant outcomes. Most of the studies are retrospective studies given the rare disease population. Acute myeloid leukemia [AML]- or acute lymphoblastic leukemia [ALL]-type multiagent chemotherapy or a lymphoma-based regimen [such as] CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] were used.

Response rates, OS, and transplant-specific outcomes for these patients were recorded. The response rates for patients were quite high. Median OS…was 18 months, median OS in the Pagano et al study was 8.7 months, and it was 7.1 months with the AML-type therapy and 12.3 months with the ALL-type therapy. The 4-year OS in the Aoki et al study was between 67% to 70%, depending on whether it was post AML-type or post ALL-type therapy. Patients in remission had an OS benefit if they got transplant.7 One study…was a prospective clinical trial looking at tagraxofusp. Patients had a response rate of 75%, 2-year OS of 40%, 2-year posttransplant OS of 66%, and 2-year OS without transplant of 30%.7 That highlights to us the outcomes for patients with and without transplant and how they are doing. Patients who get to transplant certainly benefit in terms of OS if the toxicities for transplant aren’t mitigating their QOL [quality of life].

Q: How do we manage patients with relapsed/refractory disease?

At the time of relapse, we do want to evaluate the CNS [central nervous system] for disease and need for prophylaxis if we haven’t done so. For any patient [with] relapsed or refractory [disease], a clinical trial is the preferred recommendation. For patients who haven’t received tagraxofusp, it would be an opportunity to use it. AML-, ALL-, or lymphoid-based chemotherapy can be considered if not used already. If it is an isolated lesion, you can consider local radiation, although if you are trying to do curative therapy, you might want to pause and think about what comprehensive therapy might be best suited for that patient. Systemic steroids and venetoclax [Venclexta]-based therapies might be incorporated in clinical trials.5 For many patients with BPDCN, at the time of their diagnosis, if they are a transplant candidate, we would be searching for a donor for possible transplant. I don’t know that we would be waiting until they [experienced relapse] to look for that donor.

Q: What data are there on retreatment with tagraxofusp after relapse?

I don’t know that literature perfectly. I had experience with a patient who was a Jehovah’s Witness and was [traveling] around quite a bit, and she did not complete her tagraxofusp therapy because of moving around. She had remission for some time, and because she had stopped her therapy early, we did reinitiate. And for a short time, she had a response, but then [she] ultimately lost response to tagraxofusp.

1. 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
2. Pemmaraju N, Sweet KL, Stein AS, et al. Long-term benefits of tagraxofusp for patients with blastic plasmacytoid dendritic cell neoplasm.
2022;40(26):3032-3036. doi:10.1200/JCO.22.00034 3. FDA approves tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm. FDA. December 26, 2018. Accessed August 14, 2023.
4. Elzonris. Prescribing information. Stemline Therapeutics Inc; 2018. Accessed August 14, 2023.
5. NCCN. Clinical Practice Guidelines in Oncology. Blastic plasmacytoid dendritic cell neoplasm, version 4.2023. July 11, 2023. Accessed August 14, 2023. https://tinyurl. com/2z7vn9kk
6. Bashir Q, Milton DR, Popat UR, et al. Allogeneic hematopoietic cell transplantation for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). Bone Marrow Transplant. 2022;57(1):51-56. doi:10.1038/s41409-021-01478-5
7. Pemmaraju N, Kantarjian H, Sweet K, et al. North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium: position on standards of care and areas of need. Blood. 2023;141(6):567-578. doi:10.1182/blood.2022017865
Related Videos
Expert on DLBCL
Expert on DLBCL
Expert on DLBCL
Expert on DLBCL
Expert on DLBCL
Expert on DLBCL
Expert on DLBCL
Expert on BPDCN
Expert on BPDCN
Related Content