DARZALEX FASPRO®
(daratumumab and hyaluronidase-fihj)
Medical inquiries
This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)
Medical Information
Corticosteroid Tapering Before or After DARZALEX FASPRO Administration
Last Updated: 01/09/2025
SUMMARY
- PAVO is an ongoing, phase 1b study evaluating the safety, pharmacokinetics (PK), and efficacy of DARZALEX FASPRO for subcutaneous (SC) use in patients with relapsed or refractory multiple myeloma (RRMM) who have received ≥2 prior therapy.1
- Nahi et al (2023)1 published the updated safety and efficacy results from part 3 of the PAVO study. The overall response rate (ORR) was 40.5% in the entire population, 40.0% in both the 3-week and 2-week corticosteroid taper groups and 41.7% in the 1week corticosteroid taper group. Infusion-related reactions (IRR) were reported in 5 (11.9%) patients (2-week corticosteroid taper group, n=3; 1-week corticosteroid taper group, n=2). The most common any grade treatment-emergent adverse events (TEAEs) by corticosteroid tapering groups were nausea (3-week corticosteroid taper group, n=8 [53.3%]), nasopharyngitis (2-week corticosteroid taper group, n=5 [33.3%]), and anemia, diarrhea, asthenia, and peripheral edema (1-week corticosteroid tapering group, n=4 [33.3%] each).
CLINICAL DATA
Phase 1b Study
Study Design/Methods
- Key eligibility criteria: measurable RRMM, ≥2 prior lines of therapy (including a proteasome inhibitor and an immunomodulatory drug), and an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.
- In part 3 of the study, patients received 28-day cycles of DARZALEX FASPRO (daratumumab 1800 mg with recombinant human hyaluronidase PH20 [rHuPH20] 30,000 Units SC injection [15 mL]) and either a 1-, 2- or 3-week corticosteroid tapering schedule as follows1,
2 : - 3-week taper: methylprednisolone (MP) given orally (PO)/intravenously (IV) pre-dose (cycle 1 day 1 [C1D1], 100mg; cycle 1 day 8 [C1D8], 60 mg; cycle 1 day 15 [C1D15], 30 mg) and PO post-dose (C1D1, 20 mg for 2 days; C1D8, 20 mg for 1 day; C1D15, 20 mg for 1 day).
- 2-week taper: MP given PO/IV pre-dose (C1D1, 100 mg; C1D8, 60 mg) and PO post-dose (C1D1, 20 mg for 2 days; C1D8, 20 mg for 1 day)
- 1-week taper: dexamethasone given IV pre-dose (C1D1, 20 mg)
- Dose limiting toxicities (DLTs) were assessed from C1D1 to cycle 2 day 4 for the 3week taper schedule, from C1D1 to cycle 1 day 25 for the 2-week taper schedule, and from C1D1 to cycle 1 day 11 for the 1-week taper schedule.
- Primary endpoint: safety of pre- and post-dose steroid tapering
- Key secondary endpoints: ORR and complete response (CR) per International Myeloma Working Group (IMWG) criteria
Results
Patient Characteristics
- A total of 42 patients were enrolled in part 3 of the PAVO study (3-week corticosteroid taper group, n=15; 2-week corticosteroid taper group, n=15; and 1-week corticosteroid taper group, n=12). See Table: Patient Demographics and Baseline Characteristics.
- The median duration of follow-up was 8.3 months overall, 9.2 months (range, 1.9-25.5) for the 3-week corticosteroid taper group, 11.1 months (range, 1.7-24.0) for the 2-week corticosteroid taper group, and 8.3 months (range, 0.4-13.1) for the 1-week corticosteroid taper group.
- The median number of DARZALEX FASPRO doses was 18 (range, 2-38).
- Treatment discontinuation was reported in 13 (86.7%) patients in the 3-week corticosteroid taper group, in 13 (86.7%) patients in the 2-week corticosteroid taper group, and in 7 (58.3%) patients in the 1-week corticosteroid taper group. Most discontinuations were due to progressive disease (PD) (3-week corticosteroid taper group, 10 [66.7%] patients; 2-week corticosteroid taper group, 12 [80.0%] patients; and 1-week corticosteroid taper group, 5 [41.7%] patients).
| Characteristic | 3-Week Corticosteroid Taper Group (n=15) | 2-Week Corticosteroid Taper Group (n=15) | 1-Week Corticosteroid Taper Group (n=12) | Total (n=42) |
|---|---|---|---|---|
| Age, years | ||||
| Median (range) | 66.0 (59-81) | 69.0 (52-86) | 72.5 (58-84) | 69.5 (52-86) |
| Age category, n (%) | ||||
| 18 to <65 | 4 (26.7) | 6 (40.0) | 2 (16.7) | 12 (28.6) |
| 65 to <75 | 9 (60.0) | 7 (46.7) | 5 (41.7) | 21 (50.0) |
| ≥75 | 2 (13.3) | 2 (13.3) | 5 (41.7) | 9 (21.4) |
| Median weight (range), kg | 77.0 (56.0-151.3) | 81.0 (50.0-100.0) | 76.1 (44.0-103.0) | 77.8 (44.0-151.3) |
| ECOG PS score, n (%) | ||||
| 0 | 5 (33.3) | 8 (53.3) | 4 (33.3) | 17 (40.5) |
| 1 | 9 (60.0) | 7 (46.7) | 6 (50.0) | 22 (52.4) |
| 2 | 1 (6.7) | 0 | 2 (16.7) | 3 (7.1) |
| ISS disease stagea | ||||
| I | 9 (60.0) | 8 (53.3) | 5 (41.7) | 22 (52.4) |
| II | 4 (26.7) | 2 (13.3) | 6 (50.0) | 12 (28.6) |
| III | 2 (13.3) | 5 (33.3) | 1 (8.3) | 8 (19.0) |
| Type of multiple myelomab | ||||
| IgG | 9 (60.0) | 8 (53.3) | 7 (58.3) | 24 (57.1) |
| IgA | 1 (6.7) | 3 (20.0) | 3 (25.0) | 7 (16.7) |
| Light chain | 5 (33.3) | 4 (26.7) | 2 (16.7) | 11 (26.2) |
| Median (range) time from diagnosis, years | 6.3 (2.3-19.2) | 5.6 (0.7-14.3) | 5.8 (2.0-17.2) | 5.9 (0.7-19.2) |
| Prior lines of therapy | ||||
| ≤3, n (%) | 11 (73.3) | 14 (93.3) | 6 (50.0) | 31 (73.8) |
| >3, n (%) | 4 (26.7) | 1 (6.7) | 6 (50.0) | 11 (26.2) |
| Median (range) | 2 (2-7) | 2 (2-4) | 4 (2-6) | 3 (2-7) |
| Prior ASCT, n (%) | 14 (93.3) | 12 (80.0) | 3 (25.0) | 29 (69.0) |
| Prior PI, n (%) | ||||
| Bortezomib | 15 (100) | 15 (100) | 12 (100) | 42 (100) |
| Prior IMiD | ||||
| Lenalidomide | 15 (100.0) | 14 (93.3) | 10 (83.3) | 39 (92.9) |
| Refractory to, n (%) | ||||
| Bortezomib | 6 (40.0) | 4 (26.7) | 6 (50.0) | 16 (38.1) |
| Lenalidomide | 7 (46.7) | 8 (53.3) | 9 (75.0) | 24 (57.1) |
| PI and IMiD | 4 (26.7) | 7 (46.7) | 8 (66.7) | 19 (45.2) |
| Last line of therapy | 6 (40.0) | 10 (66.7) | 9 (75.0) | 25 (59.5) |
| Cytogenetic risk profilec | n=12 | n=12 | n=7 | n=31 |
| Standard risk | 9 (75.0) | 9 (75.0) | 5 (71.4) | 23 (74.2) |
| High riskd | 3 (25.0) | 3 (25.0) | 2 (28.6) | 8 (25.8) |
| Abbreviations: ASCT, autologous stem cell transplant; ECOG PS, Eastern Cooperative Oncology Group performance status; IgA, immunoglobulin A; IgG, immunoglobulin G; IMiD, immunomodulatory drug; ISS, International Staging System; PI, proteasome inhibitor. aISS staging is derived based on the combination of serum β2-microglobulin and albumin. bBy immunofixation. cCytogenetic abnormalities are based on fluorescence in situ hybridization or karyotype testing. dHigh cytogenetic risk was defined as the presence of a t(4;14), t(14;16), or del17p abnormality. | ||||
Efficacy
- Efficacy outcomes are presented in table: Efficacy Outcomes.
- Among responders (n=17), the median time to the first and the best response was 1.0 and 1.1 months, respectively.
- The median progression-free survival (PFS) was 5.9 months, with an estimated 9-month PFS of 40.7% in the overall population.
| Parameter | 3-Week Corticosteroid Taper Group (n=15) | 2-Week Corticosteroid Taper Group (n=15) | 1-Week Corticosteroid Taper Group (n=12) | Total (n=42) |
|---|---|---|---|---|
| ORR, % | 40.0 | 40.0 | 41.7 | 40.5 |
| ≥VGPR, n (%) | 3 (20.0) | 5 (33.3) | 2 (16.7) | 10 (23.8) |
| ≥CR, n (%) | 1 (6.7) | 0 | 1 (8.3) | 2 (4.8) |
| Median time to best response, months | 1.5 | 1.9 | 1.0 | - |
| Median DOR, months | NR | 16.7 | NR | - |
| 9-month DOR rate, % | 83.3 | 83.3 | 100 | - |
| Median PFS, months | 5.9a | 4.7b | 7.4c | - |
| 9-month PFS rate, % | 40.0 | 36.1 | 46.7 | - |
| Abbreviations: CR, complete response; DOR, duration of response; NR, not reached; ORR, overall response rate; PFS, progression-free survival; VGPR, very good partial response. aMedian follow-up, 9.2 months. bMedian follow-up, 11.1 months. cMedian follow-up, 8.3 months. | ||||
- IRRs were reported in 5 (11.9%) patients during the first administration only (3-week corticosteroid taper group, n=0; 2-week corticosteroid taper group, n=3 [20.0%]; 1week corticosteroid taper group, n=2 [16.7%]).
- The median time to onset of IRRs was 79.0 minutes (range, 31-555). All IRRs resolved on the same day.
- The most common (≥5%) IRRs were chills and pyrexia (n=3 [7.1%] each). Additional IRRs included tachycardia, increased blood pressure, and oropharyngeal pain (n=1 [2.4%] each).
- All IRRs were generally mild, except for one grade 3 IRR (increased blood pressure) reported in the 2-week corticosteroid taper group.
- IRRs of grade 4, IRRs meeting DLT definition, or IRRs leading to treatment discontinuation were not reported.
- All patients experienced ≥1 TEAEs, 16 (38.1%) patients experienced serious TEAEs, and 21 (50.0%) patients experienced grade ≥3 TEAEs.
- The most common TEAEs are presented in Table: Most Common TEAEs.
- TEAEs led to death in 6 patients (3-week corticosteroid taper group, n=2 [complications from diffuse large B-cell lymphoma and PD]; 2-week corticosteroid taper group, n=1 [PD]; 1-week corticosteroid taper group, n=3 [staphylococcal pneumonia (grade 5), pulmonary embolism (grade 5), and PD]).
| TEAE | 3-Week Corticosteroid Taper Group (n=15) | 2-Week Corticosteroid Taper Group (n=15) | 1-Week Corticosteroid Taper Group (n=12) | Total (n=42) |
|---|---|---|---|---|
| Most common (≥25%) any grade TEAEs, n (%) | ||||
| Hematologic | ||||
| Anemia | 1 (6.7) | 2 (13.3) | 4 (33.3) | 7 (16.7) |
| Non-hematologic | ||||
| Nausea | 8 (53.3) | 3 (20.0) | 2 (16.7) | 13 (31.0) |
| Upper respiratory tract infection | 6 (40.0) | 3 (20.0) | 1 (8.3) | 10 (23.8) |
| Nasopharyngitis | 5 (33.3) | 5 (33.3) | 1 (8.3) | 11 (26.2) |
| Headache | 5 (33.3) | 1 (6.7) | 1 (8.3) | 7 (16.7) |
| Fatigue | 4 (26.7) | 4 (26.7) | 1 (8.3) | 9 (21.4) |
| Diarrhea | 4 (26.7) | 3 (20.0) | 4 (33.3) | 11 (26.2) |
| Pyrexia | 4 (26.7) | 2 (13.3) | 3 (25.0) | 9 (21.4) |
| Pain in extremity | 4 (26.7) | 1 (6.7) | 3 (25.0) | 8 (19.0) |
| Dizziness | 4 (26.7) | 1 (6.7) | 0 | 5 (11.9) |
| Arthralgia | 3 (20.0) | 4 (26.7) | 3 (25.0) | 10 (23.8) |
| Cough | 3 (20.0) | 4 (26.7) | 0 | 7 (16.7) |
| Erythema | 2 (13.3) | 4 (26.7) | 0 | 6 (14.3) |
| Asthenia | 1 (6.7) | 2 (13.3) | 4 (33.3) | 7 (16.7) |
| Peripheral edema | 1 (6.7) | 0 | 4 (33.3) | 5 (11.9) |
| Muscle spasms | 1 (6.7) | 0 | 3 (25.0) | 4 (9.5) |
| Most common (≥5%) grade ≥3 TEAEs, n (%) | ||||
| Hematologic | ||||
| Lymphopenia | 2 (13.3) | 0 | 1 (8.3) | 3 (7.1) |
| Anemia | 1 (6.7) | 1 (6.7) | 2 (16.7) | 4 (9.5) |
| Neutropenia | 0 | 3 (20.0) | 0 | 3 (7.1) |
| Non-hematologic | ||||
| Bone pain | 1 (6.7) | 1 (6.7) | 1 (8.3) | 3 (7.1) |
| Infections | 3 (20.0) | 2 (13.3) | 1 (8.3) | - |
| Abbreviation: TEAEs, treatment-emergent adverse events. | ||||
PK and Immunogenicity
- Within the PK-evaluable population (n=37), the mean (standard deviation [SD]) serum daratumumab concentrations at cycle 3 day 1 were 676 (314) μg/mL (overall), 604 (280) μg/mL (3-week corticosteroid taper group), 731 (382) μg/mL (2-week corticosteroid taper group), and 706 (270) μg/mL (1-week corticosteroid taper group).
- Of the immunogenicity evaluable patients (n=41), none tested positive for antidaratumumab antibodies. The reported anti-rHuPH20 antibodies (3-week corticosteroid taper group, n=6 [40.0%]; 2week corticosteroid taper group, n=3 [20.0%]; and 1week corticosteroid taper group, n=1 [9.1%]) were not neutralizing.
Literature Search
A literature search of MEDLINE®
References
| 1 | Nahi H, Usmani S, Mateos M, et al. Corticosteroid tapering is a safe approach in patients with relapsed or refractory multiple myeloma receiving subcutaneous daratumumab: part 3 of the open-label, multicenter, phase 1b PAVO study. Leukemia Lymphoma. 2023;64(2):468-472. |
| 2 |