Summary

• DARZALEX for intravenous (IV) use and DARZALEX FASPRO for subcutaneous (SC) use are not approved by the regulatory agencies for use in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Janssen does not recommend the use of DARZALEX or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.

• Dima et al (2023)¹ reported a retrospective case series where DARZALEX or DARZALEX FASPRO was used as single-agent therapy for the treatment of 7 patients with relapsed POEMS syndrome. Overall responses to DARZALEX or DARZALEX FASPRO therapy are summarized in Table: Summary of Responses to DARZALEX in Patients With Relapsed POEMS Syndrome. Three patients who received DARZALEX had grade 2 infusion-related reactions during the first infusion. No deaths were reported.
• Vaxman et al (2023)^2,3 reported on the Mayo Clinic experience of treating 16 patients with relapsed POEMS syndrome using novel agents, including DARZALEX. Among 16 DARZALEX-based therapies, 12 (75%) achieved an overall response. Four hospitalization events occurred with DARZALEX-based therapies due to pneumonia, and 3 patients experienced infusion-related reactions with the first dose of DARZALEX. No deaths were reported during treatment.
• Other relevant literature has been identified in addition to the data summarized above describing the use of DARZALEX or DARZALEX FASPRO in patients with POEMS syndrome are included in the REFERENCES section.^4-13

PRODUCT LABELING

• DARZALEX (daratumumab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf

CliniCAL Data

Dima et al (2023)¹ reported results from a retrospective case series where DARZALEX or DARZALEX FASPRO was used as single-agent therapy for the treatment of patients with relapsed POEMS syndrome from January 2017 to January 2023 at the Cleveland Clinic (CCF).

Study Design/Methods

• Patients were administered either DARZALEX (n=4; 57%) or DARZALEX FASPRO (n=3; 43%) according to the standard dosing schedule, until disease progression.
  • One patient discontinued therapy after 6 months of initiation per personal preference; another patient discontinued therapy after 29 months due to sustained benefit, per physician's discretion.
• Hematologic responses evaluated were overall response rate (ORR_H), complete hematologic response (CR_H), very good partial response (VGPR_H), partial response (PR_H), and no hematologic response (NR_H).
• Vascular endothelial growth factor (VEGF) responses (baseline must be ≥200 pg/mL) evaluated were complete response (CR_V) (normalization of plasma VEGF <87 pg/mL), partial response (PR_V) (decrease of VEGF ≥50%), and no VEGF response (NR_V; less than PR_V).
• Clinical responses evaluated were complete response (CR_C) (total resolution of symptoms), partial response (PR_C; partial resolution), and no clinical response (NR_C; no improvement in symptoms).
• Progressive disease (PD) was assessed based on either hematologic, VEGF, or clinical progression.

Results

Patient Characteristics

• A total of 7 patients diagnosed with POEMS syndrome were included in the study.
• Prior therapies were lenalidomide + dexamethasone (n=3), cyclophosphamide + dexamethasone (n=1), and cyclophosphamide + lenalidomide + dexamethasone (n=3). The median number of prior lines of therapy was 2 (range, 2-3).
• No patient had received prior upfront or salvage autologous hematopoietic cell transplantation.
• The median time from POEMS syndrome diagnosis to DARZALEX or DARZALEX FASPRO initiation was 68 months (interquartile range [IQR], 54-78), and the median time on DARZALEX or DARZALEX FASPRO was 14 months (IQR, 9-29).
• The median follow-up time from DARZALEX or DARZALEX FASPRO initiation was 28 months (IQR, 13-30).
• Baseline characteristics are presented in Table: Baseline Patient Characteristics at Diagnosis and DARZALEX or DARZALEX FASPRO Initiation.

Efficacy

• Of the 7 patients who received DARZALEX or DARZALEX FASPRO, hematologic response was evaluable in 5. VEGF response was evaluable in 4 patients. Overall responses are summarized in Table: Summary of Responses to DARZALEX or DARZALEX FASPRO in Patients With Relapsed POEMS Syndrome.
• Three patients achieved both hematologic and VEGF responses.
• Of the 6 patients who achieved clinical response, 83% had a hematologic response and 67% had a VEGF response.
• Progression was seen in 2 patients (4 months and 29 months from DARZALEX or DARZALEX FASPRO initiation). At 1 year, 86% of patients were in remission.

Safety

• No patient discontinued DARZALEX or DARZALEX FASPRO due to adverse events (AEs).
• Grade 2 infusion-related reactions were reported in 3 (43%) patients, all during the first infusion of DARZALEX.
• One (14%) patient developed a massive pulmonary embolism while on therapy; however, this was deemed unrelated to DARZALEX.
• No patients developed significant infections while on therapy.
• No death was reported during the treatment.

Vaxman et al (2023)^2,3 reported the Mayo Clinic experience of treating 16 patients with relapsed POEMS syndrome using novel agents, including DARZALEX, between 2002 and  2018.

Study Design/Methods

• All patients with POEMS seen at Mayo Clinic Rochester, Minnesota, were identified using a prospectively maintained database of patients seen at the center between January 1979 and May 2021.
• Sixteen patients were treated with 24 regimens involving DARZALEX.
• No patient was treated due to a myeloma-defining event other than a bone lesion.
• The diagnosis of POEMS syndrome was according to the following response criteria: plasma VEGF response, hematologic (M-spike, bone marrow plasma cells) response, radiologic (fluorodeoxyglucose avidity on positron emission tomography [PET]) response, and clinical response (CR).
• An overall response was considered partial response (PR) or better in any of these 4 domains without worsening in another domain.

Results

Patient Characteristics

• Baseline characteristics are presented in Table: Baseline Patient Characteristics at Diagnosis.
• The median age at novel agent administration was 63 years (IQR, 51-70), and 4 (24%) patients were ≥70 years old.  The median time from diagnosis to administration of a novel agent was 50 months (IQR, 23-122)
• Indications for treatment included clinical progression (n=6), PET/computed tomography progression only (n=5), hematologic progression only (n=3), and VEGF progression only (n=2).
• DARZALEX-based therapies were as follows: DARZALEX as part of an immunomodulator drug-steroid triplet (n=10; lenalidomide, n=6; pomalidomide, n=4), DARZALEX with dexamethasone alone (n=2), DARZALEX with cyclophosphamide (n=2), and DARZALEX as part of a quadruplet (DARZALEX, bortezomib, cyclophosphamide, and dexamethasone [DVC-d; n=1] and DARZALEX, pomalidomide, bortezomib, and dexamethasone [DPV-d; n=1]).

Efficacy

• Among the 16 DARZALEX-based therapies, overall response was achieved in 12 (75%) patients, including 9 (56%) patients with hematologic CR/VGPR, 7 (44%) patients with VEGF CR, and 5 (31%) patients with PET CR.
• Of the 2 patients who received DARZALEX and dexamethasone, 1 had PD and 1 had hematologic VGPR and PET PR.
• Three of the DARZALEX-triplet/quadruplet regimens had no response. Two regimens were administered to a refractory patient who died. The third regimen was administered to a patient who responded to DVC-d but was transitioned to DPV-d to avoid long-term alkylator use; no further response was observed, but the patient remained on the regimen for 16 months.
• TTNT was not reached with the DARZALEX-based regimens. Fifteen patients (94%) were alive.

Safety

• Overall, no patient discontinued therapy due to AEs, and no deaths occurred during treatment.
• A total of 7 hospitalizations were reported due to pneumonia, with 4 occurring in patients receiving DARZALEX-based regimens. Four patients were hospitalized due to volume overload.
• Three patients experienced infusion-related reactions with the first dose of IV DARZALEX.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 30 April 2025.