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DARZALEX FASPRO®

(daratumumab and hyaluronidase-fihj)

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DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)

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DARZALEX + DARZALEX FASPRO - Use in Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Last Updated: 02/05/2026

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 B-cell or T-cell acute lymphoblastic leukemia or acute lymphoblastic lymphoma. Janssen does not recommend the use of DARZALEX/DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
  • DELPHINUS was a phase 2 study evaluating the safety and efficacy of DARZALEX in patients between the ages of ≥1 to ≤30 years with relapsed/refractory (R/R) precursor B-cell or T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL).1
    • Hogan et al (2022)2 presented the initial results of this study evaluating the efficacy, safety, and pharmacokinetics (PK) of DARZALEX in pediatric (1 to 17 years old) or young adult (18-30 years old) patients with R/R T-cell ALL or LL. At the end of cycle 1, complete response (CR) was achieved in 10 of 24 (41.7%; 90% confidence interval [CI], 24.6-60.3) pediatric patients with T-cell ALL. The most common grade 3/4 treatment-emergent adverse event (TEAE) in pediatric T-cell ALL patients was anemia (66.7%). The most common grade 3/4 infusion-related reaction (IRR) in pediatric patients with T-cell ALL was leukopenia and abdominal pain (4.2% each). The most common grade 3/4 IRR in patients with T-cell LL was thrombocytopenia and bronchospasm (10% each).
    • Bhatla et al (2024)1 reported updated results of the phase 2 DELPHINUS study. The overall response rates (ORR) were 14.3% for pediatric patients with B-cell ALL, 83.3% for pediatric patients with T-cell ALL, 80% for young adult patients with T-cell ALL, and 50% for patients with T-cell LL. Minimal residual disease (MRD)-negativity at any time during treatment was achieved in 11 (45.8%) pediatric patients with T-cell ALL, 1 (20%) young adult patient with T-cell ALL, and 5 (50%) patients with T-cell LL. No new safety concerns were identified with DARZALEX. Any-grade and grade 3/4 TEAEs occurred in all patients (100%). The most common grade 3/4 TEAEs across the cohorts were hematologic events. Grade 3/4 infections occurred in 1 pediatric patient with B-cell ALL (grade 4 sepsis), 12 (50%) pediatric patients with T-cell ALL, 2 (40%) young adult patients with T-cell ALL, and 3 (30%) patients with T-cell LL. IRRs after the first DARZALEX infusion were reported in 4 (57.1%) pediatric patients with B-cell ALL, 16 (66.7%) pediatric patients with T-cell ALL, 4 (80%) young adult patients with T-cell ALL, and 8 (80%) patients with T-cell LL.
  • Cerrano et al (2022)3 conducted a retrospective, multicenter, observational cohort study that evaluated the efficacy and safety of DARZALEX in patients with R/R or MRD-positive ALL or LL. The ORR was 20%, and median overall survival (OS) was 4 weeks. There were no unexpected toxicities reported. One grade 2 IRR was reported in the entire cohort.
  • Other relevant literature have been referenced in addition to the data from clinical studies that are summarized below.4-12

   PRODUCT LABELING

BACKGROUND

A potential target in T-cell acute lymphoblastic leukemia is cluster of differentiation (CD)38. CD38 is a type II-transmembrane glycoprotein, and one of its main roles is in the regulation of cytoplasmic calcium flux that regulates signal transduction in immune cells.5 T-cell ALL blasts often express high CD38 levels.4 Daratumumab is a monoclonal antibody that binds to a specific epitope of CD38.5

CLINICAL DATA

DELPHINUS (ALL2005; NCT03384654) was an ongoing, open-label, multicenter, phase 2 study evaluating the safety and efficacy of DARZALEX in patients with R/R precursor B-cell or T-cell ALL or LL.1

Study Design/Methods

  • The study enrolled 47 patients and consists of 2 cohorts. The study design has been presented in the Figure: Study Design.1,2,13 

Study Design1,2,13

Abbreviations: 6-MP, 6-mercaptopurine; allo-HSCT, allogeneic hematopoietic stem cell transplant; BID, twice daily; Cmax, maximum plasma concentration; Cmin, minimum plasma concentration; CP, cyclophosphamide; CR, complete response; CrCl, creatinine clearance; CSF, cerebrospinal fluid; Dara, daratumumab; DXR, doxorubicin; EFS, event-free survival; GFR, glomerular filtration rate; GVHD, graft vs host disease; HSCT, hematopoietic stem cell transplant; IM, intramuscular; IV, intravenous; MRD, minimal residual disease; MTX, methotrexate; ORR, overall response rate; OS, overall survival; Ph+, Philadelphia chromosome positive; PO, orally; PRED, prednisone; PS, performance status; Q2W, twice a week; QD, once daily; QW, once weekly; RFS, relapse-free survival; SC, subcutaneously; ULN, upper limit of normal range; VCR, vincristine.
aB-cell cohort for stage 1: patients aged 1 to <18 years with acute lymphoblastic leukemia in ≥2nd relapse or refractory to 2 prior induction treatments with ≥5% blasts in bone marrow; stage 2: patients aged 1-30 years with acute lymphoblastic leukemia in ≥2nd relapse or refractory to 2 prior induction treatments with ≥5% blasts in bone marrow, acute lymphoblastic lymphoma in ≥2nd relapse or refractory to 2 prior induction regimens with measurable disease.
bT-cell cohort for stage 1: patients aged 1 to <18 years with acute lymphoblastic leukemia in 1st relapse or refractory to 1 prior induction/consolidation treatment with ≥5% blasts in the bone marrow; stage 2: patients aged 1-30 years with acute lymphoblastic leukemia in 1st relapse or refractory to 1 prior induction/consolidation treatment with ≥5% blasts in bone marrow, acute lymphoblastic lymphoma in 1st relapse or refractory to 1 prior induction/consolidation treatment with measurable disease, aged 1-30 years.
cPatients received age/risk-adjusted intrathecal therapy, and those who achieved CR after cycles 1 or 2 could proceed to allo-HSCT off-study.
dFor patients who achieved a CR and required a short interval of treatment prior to transplant, Dara 16 mg/kg IV could be given QW (total of 4 doses) after completion of cycle 1 or Q2W (total of 2 doses) after completion of cycles 2-6 or once after completion of cycles ≥7. There was a 2-week interval from the last dose of Dara and the start of conditioning therapy for the transplant. Other standard maintenance chemotherapy could also be given after the discontinuation of study treatment and prior to transplant.
eMaximum 2 mg.
fCycle 2 was optional to allow further treatment for those who did not achieve CR or to consolidate the response prior to HSCT.
gDuration from the date of first treatment to the first documented treatment failure or date of relapse from CR or death.

Initial Results of the DELPHINUS Study

Hogan et al (2022)2 presented the initial results of the phase 2 DELPHINUS study evaluating the efficacy, safety, and PK of DARZALEX in pediatric (1 to 17 years old) or young adult (18-30 years old) patients with R/R T-cell ALL or LL.

Results

Patient Characteristics

Baseline Patient and Disease Characteristics2
Characteristic
T-cell ALL
T-cell LL
(n=10)
Pediatric patients
(n=24)
Young adult patients
(n=5)
Median age (range), years
10 (2-17)
23 (18-25)
14.5 (5-22)
Sex, n (%)
   Male
14 (58.3)
5 (100)
9 (90)
   Female
10 (41.7)
0 (0)
1 (10)
Median time from initial diagnosis to first dose (range), years
2.5 (0.5-6.1)
0.6 (0.1-5.6)
0.8 (0.5-6)
Cycle of treatment received, n
   Cycle 1
22
5
10
   Cycle 2
18
3
6
   DARZALEX continuation
6
1
0 (0)
CNS involvement at study entry, n (%)
4 (16.7)
2 (40)
2 (20)
Abbreviation: ALL, acute lymphoblastic leukemia; CNS, central nervous system; LL, lymphoblastic lymphoma.
Efficacy
  • The median follow-up for the pediatric/young adult T-cell ALL, young adult T-cell ALL, and T-cell LL groups was 31.3 months (range, 0.8-40.1), 25.4 months (range, 2.6-25.4), and 16.4 months (range, 1.6-19) months, respectively.2
  • At the end of cycle 1, complete response (CR) was achieved in 10 of 24 (41.7%; 90% CI, 24.6-60.3) pediatric patients with T-cell ALL.2
  • Efficacy outcomes are summarized in Table: Efficacy Outcomes.2

Efficacy Outcomes2
Parameter
T-cell ALL
T-cell LL
(n=10)
Pediatric patients
(n=24)
Young adult patients
(n=5)
ORRa,b, n (%)
20 (83.3)
3 (60)
5 (50)
   90% CI
65.8-94.1
18.9-92.4
15-69.7
CRa,c, n (%)
13 (54.2)
3 (60)
4 (40)
CRia, n (%)
7 (29.2)
-
-
PRa, n (%)
-
-
1 (10)
MRD-negativitya, n (%)
10 (41.7)
1 (20)
5 (50)
Median EFSd, months (90% CI)
8.3 (5.3-20.5)
8 (2.6-NE)
2.9 (1.3-4.9)
Median OSe, months (90% CI)
9.5 (7-NE)
13.6 (4.5-NE)
4.2 (1.7-5.6)
Abbreviations: ALL, acute lymphoblastic leukemia; CI, confidence interval; CR, complete response; CRi, complete response with incomplete hematologic recovery; EFS, event-free survival; LL, lymphoblastic lymphoma; MRD, minimal residual disease; NE, not estimable; ORR, overall response rate; OS, overall survival; PR, partial response.aAt any time during treatment.bORR data after Cycle 2 will be available at end of study
cCriteria for CR: bone marrow blasts, <5%; absolute neutrophil count, >1×109/L; platelet count, >100×109/L; No evidence of circulating blasts or extramedullary disease
dEFS was defined as the time from the date of first treatment to the first documented treatment failure or date of relapse from CR or death due to any cause, whichever occurred first.
eOS was measured from the date of first treatment to the date of death due to any cause.
Safety

Grade 3/4 TEAEs (≥20%) in Pediatric Patients with T-cell ALL2
Event, n (%)
T-cell ALL
Pediatric Patients
(n=24)
Hematologic
   Anemia
16 (66.7)
   Thrombocytopenia
15 (62.5)
   Neutropenia
12 (50)
   Febrile neutropenia
11 (45.8)
   Leukopenia
9 (37.5)
Nonhematologic
   Increased alanine aminotransferase
6 (25)
   Hypokalemia
6 (25)
Abbreviation: ALL, acute lymphoblastic leukemia; TEAE, treatment-emergent adverse event.
  • Among pediatric patients with T-cell ALL, none discontinued DARZALEX due to adverse events (AEs), and 1 (4.2%) death reported due to TEAEs (brain edema and hepatic failure) related to the study treatment but unrelated to DARZALEX.2
  • IRRs of any grade were reported in 16 (66.7%) pediatric patients with T-cell ALL, 4 (80%) young adult patients with T-cell ALL, and 8 (80%) patients with T-cell LL. See Table: Infusion-Related Reactions.2

Infusion-Related Reactions2
IRR, n (%)
T-cell ALL
T-cell LL
(n=10)
Pediatric patients
(n=24)
Young adult patients
(n=5)
Any grade occurring in >10% of patients
   Abdominal pain
6 (25)
0
1 (10)
   Pyrexia
4 (16.7)
0
1 (10)
   Vomiting
3 (12.5)
0
1 (10)
   Nausea
3 (12.5)
0
0
   Cough
3 (12.5)
0
4 (40)
   Urticaria
3 (12.5)
0
0
   IRR
2 (8.3)
1 (20)
0
   Rash
1 (4.2)
1 (20)
0
   Dyspnea
1 (4.2)
0
3 (30)
   Pruritus
0
1 (20)
1 (10)
   Rhinitis
0
1 (20)
0
   Increased gammaglutamyltransferase
0
1 (20)
0
   Musculoskeletal chest pain
0
1 (2)
0
Grade 3/4 occurring in any patients
   Leukopenia
1 (4.2)
0
0
   Abdominal pain
1 (4.2)
0
0
   Thrombocytopenia
0
0
1 (10)
   Bronchospasm
0
0
1 (10)
Abbreviation: ALL, acute lymphoblastic leukemia; IRR, infusion-related reaction; LL, lymphoblastic lymphoma.
Pharmacokinetics
  • The mean serum trough concentration (Ctrough) for daratumumab was 361 (standard deviation [SD], 106) μg/mL at cycle 2 day 22 in pediatric patients with T-cell ALL.2
  • The mean cerebrospinal fluid (CSF) Ctrough of daratumumab was 1.07 μg/mL at cycle 2 day 15.2

Updated Analysis of the DELPHINUS Study

Bhatla et al (2024)1 reported updated results of the phase 2 DELPHINUS study that evaluated the efficacy and safety of DARZALEX in pediatric (1-17 years old) patients with B-cell or T-cell ALL (stage 1) and young adult (18-30 years old) patients with T-cell ALL or LL (stage 2).

Results

Patient Characteristics

Demographic and Baseline Characteristics For B-Cell and T-Cell Cohorts1
Characteristic
B-Cell ALL
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=7)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
Median age (range), years
5 (4-17)
10 (2-17)
23 (18-25)
14.5 (5-22)
Sex, n (%)
   Male
3 (42.9)
14 (58.3)
5 (100)
9 (90)
   Female
4 (57.1)
10 (41.7)
0 (0)
1 (10)
Race, n (%)
   White
5 (71.4)
18 (75)
2 (40)
8 (80)
   Asian
0 (0)
1 (4.2)
1 (20)
0 (0)
   Black/African American
0 (0)
0 (0)
1 (20)
0 (0)
   American Indian/Alaska Native
0 (0)
0 (0)
1 (20)
0 (0)
   Not reported
2 (28.6)
5 (20.8)
0 (0)
2 (20)
Hispanic/Latino ethnicity, n (%)
1 (14.3)
4 (16.7)
2 (40)
1 (10)
Median time from initial diagnosis to first dose (range), years
2.7 (1.6-4.3)
2.5 (0.5-6.1)
0.6 (0.05-5.6)
0.8 (0.5-6)
Median lines of prior systemic therapy (range)
2 (1-10)a
1 (1-1)
1 (1-1)
1 (1-1)
Median time from last progression of prior systemic therapy to first dose (range), days
15 (10-112)
8.5 (4-23)
7 (2-26)
11 (4-25)
Median blast count (range)b, %
62 (20-99)
67 (6.7-98)
71 (32.4-96.2)
4 (0-65)
Extramedullary disease, n (%)
0 (0)
4 (16.7)
2 (40)
10 (100)
CNS negative at study entry, n (%)
7 (100)
20 (83.3)
3 (60)
8 (80)
Abbreviations: ALL, acute lymphoblastic leukemia; CNS, central nervous system; LL, lymphoblastic lymphoma.
aTwo patients were listed in error as receiving only 1 prior systemic therapy. Both patients received >1 prior line of treatment; however, access to data entry was terminated after site closure and subsequent database lock, and the data could thus not be corrected.
bTumorous leukemia/lymphoma cells (n [%]) present in the bone marrow as assessed by bone marrow aspirate/biopsy.
Efficacy
  • Overall efficacy outcomes are summarized in Table: Efficacy Outcomes for B-Cell and T-Cell Cohorts.1
    • B-cell cohort1:
      • All patients received cycle 1 treatment, and 4 patients continued treatment in cycle 2.
      • All patients discontinued DARZALEX and chemotherapy; reasons for discontinuation were as follows: PD (n=5), death due to progressive disease (PD; n=1), and physician's decision (n=1).
      • No patients achieved CR within 2 treatment cycles.
      • One patient achieved complete response with incomplete hematologic recovery (CRi), 3 patients had refractory ALL, and 3 patients experienced PD as their best response.
      • This cohort was closed, and no additional efficacy endpoints were presented.
    • T-cell cohorts1,13:
      • All patients with T-cell ALL/LL were treated in cycle 1, and 18 (75%) pediatric patients with T-cell ALL, 4 (80%) young adult patients with T-cell ALL, and 6 (60%) patients with T-cell LL were treated in cycle 2.
      • Seven pediatric patients with T-cell ALL entered the DARZALEX continuation phase as a bridge to hematopoietic stem cell transplant (HSCT; 1 patient after cycle 1 and 6 patients after cycle 2). One young adult with T-cell ALL also entered after cycle 1, whereas no patient with T-cell LL received DARZALEX continuation.
      • Discontinuation of DARZALEX and backbone chemotherapy was observed in 8 pediatric patients with T-cell ALL (physician decision [n=5], PD [n=2], and death due to an AE of worsened/altered health status [n=1]), 3 young adult patients with T-cell ALL (AE [n=2] and PD [N=1]), and 4 patients with T-cell LL (physician decision [n=2], AE [n=1], and PD [n=1]).
      • Among patients with baseline extramedullary involvement, the best overall responses (all disease areas) were CRi (n=4/4) for pediatric patients with T-cell ALL, CRi (n=1/2) and refractory (n=1/2) for young adult patients with T-cell ALL, and CR (n=2/4) and PD (n=2/4) for patients with T-cell LL.
      • MRD-negativity at any time during treatment was achieved in 11 (45.8%) pediatric patients with T-cell ALL, 1 (20%) young adult patient with T-cell ALL, and 5 (50%) patients with T-cell LL.
      • A total of 18 (75%) pediatric patients with T-cell ALL received allogeneic HSCT. Similarly, 3 young adult patients with T-cell ALL (60%) and 3 patients with T-cell LL (30%) received allogeneic HSCT.
      • The MRD-negativity rate and allogeneic HSCT details are summarized in Table: MRD-Negativity Rates and Summary of Allogeneic HSCT for T-Cell Cohorts.
      • The median and observed 24-month event-free survival (EFS), relapse-free survival (RFS), and OS rates are summarized in Table: Summary of EFS, RFS, and OS Rates.

Efficacy Outcomes for B-Cell and T-Cell Cohorts1
Parameter, n (%) (90% CIa)
B-Cell ALL
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=7)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
Median treatment duration, months (range)
1.2 (0.8-2.3)
2.2 (0.5-2.9)
1.4 (1-2.1)
2.1 (0.8-2.3)
Median follow-up, months (range)
3.2 (1-4.7)
37.5 (0.8-45.7)
31.7 (2.6-31.7)
23 (1.6-25.3)
End of cycle 1
   CR
-
10 (41.7)
(24.6-60.3)b
3 (60)
(18.9-92.4)
3 (30)
(8.7-60.7)
   CRi/PRc
-
4 (16.7)
(5.9-34.2)
1 (20)
(1-65.7)
2 (20)
(3.7-50.7)
   SDc
-
-
-
3 (30)
(8.7-60.7)
   Refractory ALL
-
8 (33.3)
(17.8-52.1)
1 (20)
(1-65.7)
-
   PD
-
0 (0)
0 (0)
2 (20)
(3.7-50.7)
   NE
-
0 (0)
0 (0)
0 (0)
   Assessment not performed
-
2 (8.3)
(1.5-24)
0 (0)
0 (0)
Any time up to the end of cycle 2
   ORR
1 (14.3)
(0.7-52.1)
20 (83.3)
(65.8-94.1)
4 (80)
(34.3-99)
5 (50)
(22.2-77.8)
      CR
0 (0)
12 (50)
(31.9-68.1)
3 (60)
(18.9-92.4)
4 (40)
(15-69.7)
      CRi/PRc
1 (14.3)
(0.7-52.1)
8 (33.3)
(17.8-52.1)
1 (20)
(1-65.7)
1 (10)
(0.5-39.4)
   SDc
-
-
-
3 (30)
(8.7-60.7)
   Refractory ALL
3 (42.9)
(12.9-77.5)
2 (8.3)
(1.5-24)
1 (20)
(1-65.7)
-
   PD
3 (42.9)
(12.9-77.5)
0 (0)
0 (0)
2 (20)
(3.7-50.7)
   NE
0 (0)
0 (0)
0 (0)
0 (0)
   Assessment not performed
0 (0)
2 (8.3)
(1.5-24)
0 (0)
0 (0)
Abbreviations: ALL, acute lymphoblastic leukemia; CI, confidence interval; CR, complete response; CRi, complete response with incomplete hematologic recovery; LL, lymphoblastic lymphoma; NE, not estimable; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease.
a90% CIs were based on the Clopper-Pearson exact test.
bP=0.153.cPR and SD for patients with T-cell LL only.

MRD-Negativity Rates and Summary of Allogeneic HSCT for T-Cell Cohorts1
Parameter
T-Cell ALL
T-Cell LL
(n=10)a
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
MRD-negativity ratea, n (%) (90% CIb)
   End of cycle 1c
7 (29.2)
(14.6-47.9)
0 (0)
5 (50)
(22.2-77.8)
   End of cycle 2c
2 (8.3)
(1.5-24)
1 (20)
(1-65.7)
0 (0)
   After treatmentd
1 (4.2)
(0.2-18.3)
0 (0)
0 (0)
   At any time
11 (45.8)
(28.2-64.2)e
1 (20)
(1-65.7)
5 (50)
(22.2-77.8)
Allogeneic HSCT rate, n (%) (90% CIb)
18 (75)
(56.5-88.5)
3 (60)
(18.9-92.4)
3 (30)
(8.7-60.7)
   Median number of CD34+ cells transplanted (range), 106/kg
5.3 (0.5-264)
4.6 (1.2-10)
3.7 (3.2-7.3)
   Source of CD34+ cells transplantedf, n (%)
      Cord blood
2 (11.1)
0 (0)
1 (33.3)
      Peripheral blood
7 (38.9)
2 (66.7)
1 (33.3)
      Bone marrow
9 (50)
1 (33.3)
1 (33.3)
   Median time to engraftment (range), days
18 (10-34)
26 (21-31)
20 (11-23)
Abbreviations: ALL, acute lymphoblastic leukemia; CD, cluster of differentiation; CI, confidence interval; HSCT, hematopoietic stem cell transplant; LL, lymphoblastic lymphoma; MRD, minimal residual disease.
aMRD-negativity rate was calculated with the number of patients who were MRD-negative as the numerator and the number of patients in the all-treated analysis set as the denominator. In the T-cell LL cohort, bone marrow evaluation was only required if bone marrow disease was present at study entry; of the 5 patients with bone marrow involvement (≥5% bone marrow blasts) at baseline, 3 patients achieved MRD-negativity during the study.
b90% CIs were based on the Clopper-Pearson exact test.
cRates in cycle 1 and cycle 2 are mutually exclusive.
dAssessed before the initiation of subsequent treatment and/or HSCT.
eOne patient with pediatric T-cell ALL underwent an unscheduled MRD assessment on day 1 of cycle 3. This patient was included in the count for “at any time” but was not included at the end of cycle 1, at the end of cycle 2, or in posttreatment counts.
fPercentages were calculated with the number of patients who had CD34+ cells sourced from the indicated tissue type as the numerator and the number of patients who underwent allogeneic HSCT as the denominator.

Summary of EFS, RFS, and OS Rates1
Parameter
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
EFS
   Median, months
8.9
10.3
2.9
   24-month observed rate, %
36.1
20
20
RFSa
   Median, months
19.4
9.4
NE
   24-month observed rate, %
48.6
33.3
50
OS
   Median, months (90% CI)
10.9 (6.7-NE)
12 (4.5-NE)
4.2 (1.7-5.6)
   24-month observed rate, %
41.3
25
20
Abbreviations: ALL, acute lymphoblastic leukemia; CR, complete response; CI, confidence interval; EFS, event-free survival; LL, lymphoblastic lymphoma; NE, not estimable; OS, overall survival; RFS, relapse-free survival.aPatients who achieved CR.
Safety
  • No new safety concerns were identified with DARZALEX.1 Any-grade and grade 3/4 TEAEs occurred in all patients (100%) and are summarized in Table: TEAEs in B-Cell and T-Cell Cohorts.1
    • The most common grade 3/4 TEAEs across cohorts were hematologic events.
    • Grade 3/4 infections occurred in 1 pediatric patient with B-cell ALL (grade 4 sepsis), 12 (50%) pediatric patients with T-cell ALL, 2 (40%) young adult patients with T-cell ALL, and 3 (30%) patients with T-cell LL.
    • No specific infections occurred in >2 patients across the T-cell cohorts.
    • Serious TEAEs occurred in 3 (42.9%) pediatric patients with B-cell ALL (febrile neutropenia, multiple organ dysfunction syndrome, and respiratory distress [n=1]; febrile neutropenia [n=1]; and febrile neutropenia, sepsis, and death [n=1]), 16 (66.7%) pediatric patients with T-cell ALL, 4 (80%) young adult patients with T-cell ALL, and 7 (70%) patients with T-cell LL. Events in ≥2 patients in the T-cell cohorts included pyrexia, febrile neutropenia, septic shock, hyperbilirubinemia, neutropenia, diarrhea, stomatitis, and cellulitis.
    • DARZALEX discontinuation due to TEAEs occurred in 1 pediatric patient with T-cell ALL (brain edema/hepatic failure), 2 young adult patients with T-cell ALL (hyperbilirubinemia, neutropenia, septic shock, and thrombocytopenia [n=1]; psychotic disorder [n=1]), and 1 patient with T-cell LL (seizure). None of the events were attributed to DARZALEX.
    • Death due to TEAEs was reported in 2 pediatric patients with B-cell ALL (multiorgan dysfunction syndrome [n=1]; unknown cause [n=1]), 2 pediatric patients with T-cell ALL (brain edema/hepatic failure due to backbone chemotherapy [n=1]; worsened or altered general health status [n=1]), and 1 patient with T-cell LL (pleural effusion). None of the deaths were attributed to DARZALEX.
    • IRRs after the first DARZALEX infusion were reported in 4 (57.1%) pediatric patients with B-cell ALL, 16 (66.7%) pediatric patients with T-cell ALL, 4 (80%) young adult patients with T-cell ALL, and 8 (80%) patients with T-cell LL.
      • The most common IRRs were cough (42.9%) in pediatric patients with B-cell ALL; abdominal pain (20.7%), vomiting (13.8%), and pyrexia (13.8%) in patients with T-cell ALL; and cough (40%) and dyspnea (30%) in patients with T-cell LL.
    • Throughout the study, none of the 36 evaluable patients tested positive for anti-DARZALEX antibodies.

TEAEs in B-Cell and T-Cell Cohorts1
TEAE, n (%)
B-Cell ALL
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=7)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
Any-grade TEAE
7 (100)
24 (100)
5 (100)
10 (100)
Any-grade TEAEs in >50% of patients in any cohort
   Febrile neutropenia
5 (71.4)
12 (50)
3 (60)
6 (60)
   Anemia
4 (57.1)
16 (66.7)
2 (40)
10 (100)
   Thrombocytopenia
2 (28.6)
18 (75)
3 (60)
9 (90)
   Neutropenia
2 (28.6)
15 (62.5)
2 (40)
6 (60)
   Leukopenia
3 (42.9)
9 (37.5)
1 (20)
5 (50)
   Vomiting
2 (28.6)
15 (62.5)
2 (40)
5 (50)
   Abdominal pain
2 (28.6)
12 (50)
3 (60)
4 (40)
   Stomatitis
0 (0)
11 (45.8)
3 (60)
7 (70)
   Constipation
2 (28.6)
6 (25)
4 (80)
2 (20)
   Pyrexia
4 (57.1)
17 (70.8)
3 (60)
8 (80)
   Fatigue
0 (0)
3 (12.5)
3 (60)
1 (10)
   Hyperbilirubinemia
0 (0)
8 (33.3)
4 (80)
4 (40)
   ALT increased
3 (42.9)
10 (41.7)
3 (60)
5 (50)
   AST increased
2 (28.6)
5 (20.8)
3 (60)
5 (50)
   Blood AP increased
0 (0)
0 (0)
4 (80)
0 (0)
   Hypoalbuminemia
0 (0)
12 (50)
3 (60)
5 (50)
   Hyponatremia
0 (0)
6 (25)
4 (80)
2 (20)
   Cough
3 (42.9)
7 (29.2)
0 (0)
5 (50)
   Hypoxia
2 (28.6)
4 (16.7)
3 (60)
0 (0)
Grade 3/4 TEAE
7 (100)
24 (100)
5 (100)
10 (100)
Grade 3/4 TEAEs in >40% of patients in any cohort
   Febrile neutropenia
5 (71.4)
12 (50)
3 (60)
5 (50)
   Anemia
3 (42.9)
16 (66.7)
1 (20)
10 (100)
   Leukopenia
3 (42.9)
9 (37.5)
1 (20)
5 (50)
   Neutropenia
2 (28.6)
15 (62.5)
2 (40)
6 (60)
   Thrombocytopenia
1 (14.3)
15 (62.5)
3 (60)
9 (90)
Serious TEAE
3 (42.9)
16 (66.7)
4 (80)
7 (70)
TEAE leading to DARZALEX discontinuation
0 (0)
1 (4.2)
2 (40)
1 (10)
Death due to TEAEs
2 (28.6)
2 (8.3)
0 (0)
1 (10)
IRRs
   Grade 1/2
4 (57.1)
15 (62.5)
4 (80)
7 (70)
   Grade 3
0 (0)
1 (4.2)
0 (0)
1 (10)
Abbreviations: ALL, acute lymphoblastic leukemia; ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; IRR, infusion-related reaction; LL, lymphoblastic lymphoma; TEAE, treatment-emergent adverse event.
Pharmacokinetics
  • B-cell cohort13:
    • The mean peak serum concentration for daratumumab showed an increase of approximately 1.64-fold from 302 μg/mL (SD, 83.1) on day 1 of cycle 1 at end of infusion (EOI) to 494 μg/mL (SD, 184) on day 1 of cycle 2 at EOI, indicating accumulation after weekly daratumumab administration.
    • The mean serum daratumumab concentration at the end of treatment was 58.9 μg/mL (SD, 50.7), which decreased to 11.5 μg/mL (SD, 6.06) by post-treatment week 8.
    • Overall, the serum daratumumab concentrations observed in the B-cell ALL cohort were comparable to those seen in adult patients with multiple myeloma.
    • After weekly administration of daratumumab, the mean CSF concentration was 0.573 μg/mL (SD, 0.545) on day 1 of cycle 2 prior to dosing, significantly lower than the corresponding serum concentration, indicating no drug accumulation in the CSF.
  • T-cell cohorts1:
    • In pediatric patients with T-cell ALL, the mean peak serum concentration for daratumumab showed an increase of approximately 2.9-fold from 263 μg/mL (SD, 8.18) on day 1 of cycle 1 at EOI to 763 μg/mL (SD, 185) on day 22 of cycle 2 at EOI, indicating accumulation after weekly daratumumab administration.
      • The mean Ctrough prior to dosing in pediatric patients with T-cell ALL was 324 μg/mL (SD, 184) and 369 μg/mL (SD, 105) on days 1 and 22 of cycle 2, respectively.
      • Comparable results were obtained in the young adult T-cell ALL and T-cell LL cohorts.
    • All but 1 pediatric patient with T-cell ALL provided a post baseline CSF PK sample, resulting in a CSF PK-evaluable population of 38 patients.
      • The daratumumab CSF concentration was similar in both the pediatric T-cell ALL and T-cell LL cohorts.
      • Among young adults with T-cell ALL, a lower daratumumab CSF concentration was observed over time.
      • The mean CSF concentration in pediatric patients with T-cell ALL was 0.907 μg/mL (SD, 1.96) on day 15 of cycle 1 before dosing and 0.934 μg/mL (SD, 0.549) on day 15 of cycle 2 before dose.

Multicenter, Retrospective, Observational Study

Cerrano et al (2022)3 conducted a retrospective, multicenter, observational cohort study evaluating the efficacy and safety of DARZALEX in patients with R/R or MRD-positive T-cell or B-cell ALL or LL.

Study Design/Methods

  • Patients received DARZALEX (16 mg/kg IV weekly for first the 8 doses; then once every 2 weeks for 8 doses; then once monthly until PD) alone or in combination with chemotherapy.3
  • Inclusion criteria: Adult and pediatric patients with R/R or MRD-positive T- or B-lineage ALL or acute LL who received ≥1 dose of DARZALEX were included.3
  • Co-primary endpoints: ORR (defined as the proportion of patients achieving CR or partial response (PR) or proportion of patients who were MRD-positive at baseline achieving MRD-negativity) and OS.3
    • CR was defined as bone marrow blasts count <5% without evidence of extramedullary manifestations and PR was defined as bone marrow blasts count ≥5% and <25% with a reduction in leukemic involvement by ≥50%.
  • Additional endpoints: safety and bridge to allo-HSCT.3

Results

Patient Characteristics
  • A total of 20 patients were included in this study (T-cell ALL, n=13; B-cell ALL, n=4; acute LL, n=2 [B-cell, n=1; T-cell, n=1]). Baseline patient and disease characteristics are summarized in Table: Baseline Characteristics.3

Baseline Characteristics3
Characteristic
N=20
Male, n (%)
17 (85)
Age at initiation of DARZALEX, median (range), years
35 (8-73)
   <18 years, n (%)
3 (15)
Patients with ALL, n (%)
18 (80)
   T-cell
13 (65)
   Early T precursor
4 (20)
   B-cell
4 (20)
   Mixed phenotype acute leukemia
1 (5)
Patients with acute LL, n (%)
2 (10)
   T-cell
1 (5)
   B-cell
1 (5)
Prior lines of treatment, median (range)
3 (1-4)
Prior allo-HSCT, n (%)
9 (45)
Disease status at initiation of DARZALEX, n (%)
   Isolated bone marrow relapse
8 (40)
   Bone marrow relapse with extramedullary involvement
8 (40)
   Extramedullary disease with MRD positivity
2 (10)
   Extramedullary disease only
1 (5)
   MRD-positive CR
1 (5)
ECOG status at initiation of DARZALEX, median (range)
2 (0-4)
Concomitant chemotherapy, n (%)
9 (45)
Time from diagnosis to initiation of DARZALEX, median (range), months
13 (7-28)
Abbreviations: ALL, acute lymphoblastic leukemia; allo-HSCT, allogeneic hematopoietic cell transplant; CR, complete response; ECOG, Eastern Cooperative Oncology Group; LL, lymphoblastic lymphoma; MRD, minimal residual disease.
  • DARZALEX was administered as monotherapy in 11 patients (including 1 patient who received DARZALEX after a short dexamethasone pre-phase) and in combination with chemotherapy in 9 patients.3
Efficacy
  • The ORR was 20% (MRD-negative CR, n=2; MRD-positive CR, n=1; PR, n=1). Efficacy outcomes are summarized in Table: Efficacy Outcomes.3

Efficacy Outcomes3
Parameter
N=20
Response to DARZALEX
   Responders, n (%)
4 (20)
      MRD-negative CR
2 (10)
      MRD-positive CR
1 (5)
      PR
1 (5)
   Non-responders, n (%)
16 (80)
      SD
2 (10)
      PD
12 (60)
      NE
2 (10)
Post-DARZALEX allo-HSCT, n (%)
4 (20)
   In patients with CR/PR
2 (10)
Duration of treatment, median (range), weeks
2 (2-120)
Discontinued treatment, n (%)
19 (95)
Abbreviations: allo-HSCT, allogeneic hematopoietic cell transplant; CR, complete response; MRD, minimal residual disease; NE, not estimable; PD, progressive disease; PR, partial response; SD, stable disease.
  • Median time to response was 4 weeks (after 2-6 infusions of DARZALEX).3
  • Of the 4 patients who responded, 3 had T-lineage ALL and received DARZALEX monotherapy. Factors affecting response to DARZALEX are summarized in Table: Factors Affecting Response to DARZALEX.3

Factors Affecting Response to DARZALEX3
Parametera
Responders
(n=4)
Non-responders
(n=16)
P value
Sex, n (%)
-
-
1
   Male
4 (23.5)
13 (76.5)
-
   Female
0 (0)
3 (100)
-
Age, years, median (range)
34 (25-45)
35.5 (8-73)
0.92
T-lineage, n (%)
3 (21.4)
11 (78.6)
1
B-lineage, n (%)
1 (20)
4 (80)
1
Lymphoblastic lymphoma, n (%)
1 (50)
1 (50)
0.37
Extramedullary disease, n (%)
2 (18.2)
9 (81.8)
1
Bone marrow MRDb, n (%)
2 (66.7)
1 (33.7)
0.088
Bone marrow relapse, n (%)
1 (6.2)
15 (93.8)
0.013
Previous allo-HSCT, n (%)
2 (22.2)
7 (77.8)
1
Previous lines of treatment, n (%)
-
-
0.022
   1
2 (100)
0 (0)
-
   2
1 (25)
3 (75)
-
   3
1 (9.1)
10 (90.9)
-
   4
0 (0)
3 (100)
-
White blood cells, median (range), ×109/L
3.36 (3-4.3)
4.66 (0.1-39.4)
0.91
Hemoglobin, median (range), g/dL
10 (10-11)
9.5 (8-13)
0.25
Platelets, median (range), ×109/L
151 (70-233)
27 (1-199)
0.019
Peripheral blood blasts, median (range), %
0 (0-0)
24 (0-98)
0.034
Bone marrow blasts, median (range), %
2 (0-78)
50 (1-100)
0.099
ECOG score, n (%)
-
-
0.019
   0
2 (100)
0 (0)
-
   1
2 (40)
3 (60)
-
   2
0 (0)
4 (100)
-
   3
0 (0)
7 (100)
-
   4
0 (0)
1 (100)
-
Abbreviation: allo-HSCT, allogeneic hematopoietic stem cell transplantation; ECOG, Eastern Cooperative Oncology Group; MRD, minimal residual disease.
aDisease status and patient characteristics were evaluated at initiation of DARZALEX therapy.
bIncludes patients in complete remission with isolated measurable residual disease positivity and those with extramedullary relapse and measurable residual disease positivity in the bone marrow.
  • No significant association between CD38 expression on lymphoblasts at baseline and response was observed.3
  • In the entire cohort, median OS was 4 weeks, and 3-month OS rate was 25%.3
Safety
  • There were no unexpected toxicities observed and 1 grade 2 infusion-related reaction was reported with DARZALEX.3
  • At the final follow-up, 2 patients (both with T-cell ALL) were alive and in CR and 2 patients died due to relapse and treatment-related complications after allo-HSCT, respectively.3

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
03 February 2026. The search was limited to publications from 2020 to present. For streamlining purposes, case reports have been excluded.

 

References

Show
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2 Hogan L, Bhatla T, Teachey D, et al. Efficacy and safety of daratumumab (DARA) in pediatric and young adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL): initial results from the phase 2 DELPHINUS study. 2022;(Oral Presentation).  
3 Cerrano M, Bonifacio M, Olivi M, et al. Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia: a retrospective observational Campus ALL study. Haematologica. 2022;107(4):996-999.  
4 Cerrano M, Castella B, Lia G, et al. Immunomodulatory and clinical effects of daratumumab in T-cell acute lymphoblastic leukaemia. Br J Haem. 2020;191:e28-32.  
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8 Shi H, Yang F, Cao M, et al. Daratumumab and venetoclax combined with CAGE for late R/R T-ALL/ LBL patients: Single-arm, open-label, phase I study. Annals of Hematology. 2024.  
9 Dai Y, Luo L, Wei Z, et al. The clinical efficacy of a daratumumab-based regimen in relapsed/refractory acute leukemia: a single-center experience. Ann Hematol. 2024;103(10):4057-4063.  
10 Muller K, Vogiatzi F, Winterberg D, et al. Combining daratumumab with CD47 blockade prolongs survival inpreclinical models of pediatric T-ALL. 2022.  
11 Easdale S, Anthias C, Garnett C, et al. A single centre experience with daratumumab in relapsed refractory T-ALL. Bone Marrow Transplant. 2025;60:728-729.  
12 Peng L, Ren J, Dai Y, et al. Combination of venetoclax and daratumumab plus CAG regimen is an effective transplant bridging regimen in adult T-cell acute lymphoblastic leukemia with positive minimal residual disease. Hemasphere. 2025;9(S1):2238-2239.  
13 Bhatla T, Hogan LE, Teachey DT, et al. Supplement to: Daratumumab in pediatric relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma: the DELPHINUS study. Blood. 2024;144:2237-2247.