SUMMARY

• DARZALEX for intravenous (IV) use and DARZALEX FASPRO for subcutaneous (SC) use are not approved by the regulatory agencies for use in combination with ixazomib for the treatment of multiple myeloma (MM). Johnson & Johnson does not recommend the use of DARZALEX or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
• HOVON-143¹ was a prospective, multicenter, phase 2 study evaluating the efficacy, tolerability, and safety of DARZALEX, ixazomib, and dexamethasone (D-Id) in unfit or frail patients with newly diagnosed multiple myeloma (NDMM).
  • Smits et al (2025)² reported long-term outcomes of the HOVON-143 trial after a median follow-up of >5 years in frail patients. The median progression-free survival (PFS) was 13.8 months (95% confidence interval [CI], 10.1-21.4), and the median overall survival (OS) was 34.0 months (95% CI, 28.1-53.2). Subgroup analyses showed shorter PFS and OS in ultra-frail patients compared with those considered frail based on age alone. Grade ≥3 hematologic adverse events (AEs) were reported in 35% of patients (mostly thrombocytopenia), and severe infections (grade ≥3) were reported in 23% of patients.
• DeRIVE (NCT03942224)³ is an ongoing phase 2 study evaluating the efficacy and safety of a combination induction therapy with D-Id only (arm A) vs DARZALEX in combination with bortezomib and dexamethasone (D-Vd) followed by D-Id (arm B) in patients with NDMM.
  • Nooka et al (2025)⁴ presented the final safety and efficacy outcomes of the DeRIVE study. The post-induction very good partial response or better (≥VGPR) rate was 28% in arm A vs 56.5% in arm B (P=0.043). The AE profile was similar across arms, with grade 3/4 AEs occurring in 2 patients (13 events) in arm A vs 3 patients (4 events) in arm B.
• Alliance Foundation Trial 41 (NCT04009109)⁵ is a multicenter, randomized, phase 2 study comparing maintenance therapy with DARZALEX FASPRO, lenalidomide, and ixazomib (D-RI) vs lenalidomide after induction with DARZALEX FASPRO, lenalidomide, ixazomib, and dexamethasone (D-RId) in transplant-ineligible/deferred patients with NDMM.
  • Yee et al (2025)⁶ presented safety and efficacy outcomes from the combined arms after 12 cycles of induction therapy. The PFS rate at 12 months was 92% (95% CI, 86.1-98.4); the OS rate at 12 months was 93.6% (95% CI, 88.3-99.2). The most common grade ≥3 hematologic AE was neutropenia (16.5%) and the most common grade ≥3 non-hematologic AE was infection (18.9%).
• C16047 (NCT03439293)⁷ was an open-label, multicenter, phase 2 study evaluating the safety and efficacy of DARZALEX in combination with ixazomib (D-I) and D-Id in patients with relapsed and/or refractory multiple myeloma (RRMM).
  • Delimpasi et al (2024)⁸ reported the final analysis of the C16047 study. In all response-evaluable patients, the very good partial response (VGPR) or better rate was 30.5% and the overall response rate (ORR) was 64.4%. Overall, the median PFS was 16.8 months (95% CI, 10.1-23.7). The most common any-grade treatment-emergent adverse event (TEAE) was diarrhea (42.6%). The most common grade ≥3 TEAEs were thrombocytopenia and pneumonia (11.5% each).
• DARIA (NCT03746652)⁹ was a prospective, open-label, multicenter, phase 2 study evaluating the effectiveness of D-Id as a second-line therapy in patients with RRMM who have received prior treatment with lenalidomide-based regimens.
  • Terpos et al (2024)¹⁰ reported the efficacy and safety results of the DARIA study. The ORR was 64%. The median PFS was 8.1 months (95% CI, 5.2-15.8), and the median OS was 39.2 months (95% CI, 17.439.3). The most frequent grade 3/4 AE was thrombocytopenia (18.0%).
• IDARA (IFM 2018-02) (NCT03757221)¹¹ is an ongoing, open-label, multicenter, phase 2 study evaluating the efficacy and safety of D-I without dexamethasone in elderly patients with RRMM.
  • Touzeau et al (2023)¹² presented the results of the phase 2 IFM 2018-02 study at a data cutoff date of January 19, 2023. The ≥VGPR rate was 32% in all evaluable patients. The grade ≥3 AEs reported were thrombocytopenia (n=10), other cytopenia (n=8), infection (n=5), hypertension (n=3), gastrointestinal disorder (n=5), and infusion-related reactions (IRRs; n=2).
• 180638 (NCT03590652)¹³ is an ongoing, multicenter, phase 2 study evaluating the ORR of patients with MM to DARZALEX in combination with ixazomib, pomalidomide, and dexamethasone (D-IPd).
  • Kumar et al (2023)¹⁴ reported the interim analysis (as of October 2023) of the 180638 study in patients with early RRMM. The ORR was 82%. The most frequent grade ≥3 TEAE was neutropenia (63%).
• Other relevant analyses were identified and are listed in the References section for your information.^15-18 

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

Phase 2 Study of D-Id in Transplant-Ineligible Frail or Unfit Patients With NDMM

HOVON-143 (EudraCT number: 2016-002600-90)¹ was a prospective, multicenter, phase 2 study evaluating the efficacy, tolerability, and safety of D-Id in unfit or frail patients with NDMM. Smits et al (2025)² reported long-term outcomes (>5 years of median follow-up) in frail patients in the induction and maintenance phases of the HOVON-143 study.

Study Design/Methods

• Patients with NDMM who were classified as frail based on the IMWG Frailty Index (IMWG-FI) were included; they received 9 cycles of the following induction treatment (28-day cycles)²
  • DARZALEX: 16 mg/kg IV on days 1, 8, 15, and 22 during cycles 1-2; on days 1 and 15 during cycles 3-6; and on day 1 during cycles 7-9
  • Ixazomib: 4 mg on days 1, 4, and 15
  • Dexamethasone: 20 mg during cycle 1-2, and 10 mg thereafter on the days which DARZALEX is administered
• Patients received 8-week cycles of the following maintenance treatment until disease progression up to a maximum of 2 years²:
  • DARZALEX: on day 1
  • Ixazomib: on days 1, 8, 15, 29, 36, and 43
  • Dexamethasone: on day 1
• Primary endpoint: ORR²
• Key secondary endpoints: PFS, PFS on subsequent line of treatment (PFS2), OS, tolerability, and safety²
• Frailty subgroups²:
  • Frail based on age alone (>80 years, no impairments/comorbidities)
  • Frail based on impairments (<80 years with impairments and/or comorbidities)
  • Ultra-frail (>80 years with impairments and/or comorbidities)

Results

Patient Characteristics and Treatment Disposition

• The baseline patient characteristics are summarized in Table: Key Baseline Characteristics.
• Among 65 frail patients (IMWG-FI score ≥2), 64 started induction and 41 (63%) completed all 9 cycles.²
  • Between induction and maintenance, 9 patients discontinued therapy (PD [n=5], toxicity [n=1], other reasons [n=3]).
• A total of 32 patients (50%) entered maintenance and 11 (34%) completed 2 years of therapy.²

Efficacy

• Detailed efficacy results are summarized in Table: Efficacy Outcomes Across Frailty Subgroup.
• Of the 46 patients eligible for second line treatment, 37 (80%) received subsequent therapy.²
  • Lenalidomide-based regimens comprised the most common subsequent therapies (89%).

Safety

• Grade ≥3 hematologic AEs occurred in 21 patients (35%; most commonly thrombocytopenia).²
• Severe infections (grade ≥3) were reported in 15 patients (23%).²
• Polyneuropathy of any grade occurred in 25 patients (38%; grade 1, 12%; grade 2, 18%; grade 3, 8%) and did not differ across frail subgroups.²
• Cumulative incidence and annualized rates of AEs did not differ between frailty subgroups.²
• When corrected for time on protocol, severe infections (grade ≥3) occurred more frequently in patients who were frail based on impairments and ultra-frail vs patients who were frail based on age alone.²

Phase 2 Study of D-Id With or Without Bortezomib in Patients With NDMM

DeRIVE (NCT03942224)³ is an ongoing phase 2 study evaluating the efficacy and safety of a combination induction therapy with D-Id with or without bortezomib for treating patients with NDMM. Nooka et al (2025)⁴ presented the final safety and efficacy results of the DeRIVE study at a data cutoff of May 1, 2025.

Study Design/Methods

• Inclusion criteria: NDMM, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and no prior exposure to ixazomib or anti-cluster of differentiation (CD)38 therapy.³
• Patients randomized to arm A received the following treatment regimen (D-Id × 8 cycles)⁴:
  • DARZALEX: 16 mg/kg IV on days 1, 8, 15, and 22 every 28 days for 2 cycles; then on days 1 and 15 every 28 days for 6 cycles and every 28 days during maintenance (or DARZALEX FASPRO 1800 mg SC at the same schedule)
  • Ixazomib: 4 mg orally (PO) on days 1, 8, and 15 every 28 days
  • Dexamethasone: 40 mg PO on days 1, 8, 15, and 22 every 28 days
• Patients randomized to arm B received the following treatment regimen (D-Vd × 3 cycles followed by D-Id × 5 cycles)⁴:
  • DARZALEX: 16 mg/kg IV on days 1, 8, 15, and 22 every 28 days for 2 cycles; then on days 1 and 15 every 28 days for 6 cycles and every 28 days during maintenance (or DARZALEX FASPRO 1800 mg SC at the same schedule)
  • Bortezomib: 1.3 mg/m² SC on days 1, 4, 8, and 11 every 21 days
  • Dexamethasone: 40 mg PO on days 1, 8, 15, and 22 every 28 days
• Transplant-eligible patients could receive a transplant after cycle 8.
• During the maintenance phase, patients received D-Id for a total of 32 cycles.
• Primary endpoint: ≥VGPR rate post-induction cycle 8
• Key secondary endpoints: ORR, PFS, and OS

Results

Patient Characteristics

• For key baseline patient and disease characteristics, see Table: Key Baseline Patient and Disease Characteristics.

Efficacy

• The median follow-up for PFS was 53.22 months (arm A) and 55.89 months (arm B); the median follow-up for OS was 60.22 months (arm A) and 60.97 months (arm B).
• Median PFS and OS were not reached in both arms.
• The 60-month PFS rate for arm B was 80%.
• No OS events occurred in arm B with >60 months of follow-up.
• Efficacy outcomes are summarized in Table: Efficacy and Response Outcomes by Treatment Arm.

Safety

• The AE profile was similar across both arms; grade 3/4 study-related AEs occurred in 2 patients (13 events) in arm A vs 3 patients (4 events) in arm B.
• One grade 3/4 peripheral neuropathy (PN) event was reported in arm A. The incidence of grade 1/2 PN was higher in arm B.
• Two secondary primary malignancies were reported in arm B (prostate cancer and esophageal adenocarcinoma).

Phase 2 Study of D-RId in Transplant-Ineligible/Deferred Patients With Early NDMM

Alliance Foundation Trial 41 (NCT04009109)⁵ is a multicenter, randomized, phase 2 study comparing maintenance therapy with D-RI vs lenalidomide after induction with D-RId for 12 cycles in transplant-ineligible/deferred patients with NDMM. Yee et al (2025)⁶ presented safety and efficacy outcomes from this study. This analysis focused on outcomes of induction therapy after 12 cycles, with both arms combined, due to the reduced patient number in the trial.

Study Design/Methods

• Key inclusion criteria: NDMM, ECOG PS 0-2, not considered a candidate for high-dose chemotherapy and autologous stem cell transplant (ASCT) or deferred.
• Patients were stratified based on the presence of high-risk features (International Staging System [ISS] stage III or high-risk cytogenetics.
• All patients received the following induction regimen (D-RId × 12 cycles [28-day cycle]):
  • DARZALEX FASPRO: 1800 mg SC weekly during cycles 1 to 2; on days 1 and 15 during cycles 3 to 6; and every 4 weeks from cycle 7 onward
  • Lenalidomide: 15 mg PO on days 1 to 21
  • Ixazomib: 4 mg PO on days 1, 8, and 15
  • Dexamethasone: 20 mg PO on days 1, 2, 8, 9, 15, 16, 22, and 23 (dose reduced to weekly for patients aged ≥75 years)
• Patients received the following treatment regimen during the maintenance phase:
  • Arm A: lenalidomide 10 mg PO on days 1 to 21 for 24 cycles
  • Arm B: DARZALEX FASPRO 1800 mg SC on day 1; lenalidomide 10 mg PO on days 1 to 21; and ixazomib 3 mg PO on days 1, 8, and 15 for 24 cycles
• Primary endpoint: PFS

Results

Patient Characteristics

• Patient were enrolled from October 2020 to December 2023; accrual was impacted by the coronavirus disease 2019 (COVID-19) pandemic.
• At the data cutoff date of July 14, 2025, 79 patients were enrolled out of the planned 188 patients.
• Patient characteristics are summarized in Table: Patient Demographics and Characteristics.

Efficacy

• The PFS rate at 12 months was 92% (95% CI, 86.1-98.4).
• The OS rate at 12 months was 93.6% (95% CI, 88.3-99.2).
• Response outcomes are presented in Table: Response Outcomes.
• PFS outcomes by FISH and frailty are presented in Table: 12-Month PFS Outcomes.

Safety

• Overall safety outcomes are summarized in Table: Treatment-Emergent Adverse Events.
• Grade ≥3 AEs occurred in 63% of nonfrail patients vs 85% of frail patients (P=0.043).

Phase 2 Study of D-Id in Patients With RRMM

C16047 (NCT03439293)⁷ was an open-label, multicenter, phase 2 study evaluating the safety and efficacy of D-I and D-Id in patients with RRMM. Delimpasi et al (2024)⁸ reported the final analysis of this study.  

Study Design/Methods

• Prospective, single-arm, open-label, multicenter, phase 2 study.
• Patients received 28-day cycles of the following until disease progression or unacceptable toxicity:
  • DARZALEX: 16 mg/kg IV once weekly (QW) during cycles 1-2, once every two weeks (Q2W) during cycles 3-6, and once every 4 weeks (Q4W) thereafter
  • Ixazomib: 4 mg PO on days 1, 8, and 15 of each cycle
  • Dexamethasone: 20 mg IV (required prior to first DARZALEX dose only)/PO on days 1, 2, 8, 9, 15, 16, 22, and 23.
  • Antipyretics, antihistamines, and montelukast were administered before DARZALEX to reduce the risk of IRRs.
  • DARZALEX dose reductions were not permitted.
• Primary endpoint: ≥VGPR
• Key secondary endpoints: ORR, PFS, time to progression (TTP), OS, time to response (TTR), duration of response (DOR), safety, and collection of ixazomib plasma concentration-time data.
• Exploratory objectives included: minimal residual disease (MRD) detection in patients with complete response (CR), health-related quality of life (HRQoL), and clinical efficacy in subgroups of high-risk and expanded high-risk cytogenetic abnormalities.

Results

Patient Characteristics

• Details of the 61 patients from 19 study centers in 6 countries enrolled from June 8, 2018 to July 18, 2019 are presented in Table: Patient Demographics and Baseline Characteristics.
• At the data cut-off of January 1, 2022, 15 (24.6%) patients were ongoing treatment, while study treatment was discontinued in 46 patients due to progressive disease (PD; n=36), AE (n=7), and physician decision/patient withdrawal (n=3).

Efficacy

• At final analysis, 59 patients were included in the all-response evaluable patient population with response rates detailed in Table: Confirmed Best Reponses in All Response-Evaluable Patients.  
  • Median time to best response of partial response (PR) or greater was 1.0 months (95% CI, 1.0-1.9)
  • Median DOR was 24.0 months (95% CI, 15.9-not reached [NR])
  • Among 18 patients who achieved ≥VGPR,
    • Median time to best response was 4.2 months (95% CI, 1.9-5.5)
    • Median DOR was not estimable (95% CI, 11.8-NR)
• Prespecified subgroups response rates are detailed in Table: Confirmed Best Reponses in Patient Subgroups.  

• PFS details are summarized in Table: PFS in Overall, High-Risk Cytogenetics, Expanded High-Risk Cytogenetics, and Lenalidomide-Refractory Patients.
• At a median follow-up of 30.9 months (95% CI, 27.9-33.8), the median TTP in all patients was 21.1 months (95% CI, 10.2-27.9) with 35 events.
• At a median follow-up of 32.5 months (95% CI, 30.6-33.6), the median OS was not reached with 18 deaths.
  • The 1-year OS rate was 91.4% (95% CI, 80.6-96.3).

• MRD was evaluated in 8 patients who achieved a confirmed CR and maintained it at 6 and 12 cycles after initial CR.
  • Overall, 4 patients achieved MRD-negativity at any timepoint during treatment.
• Patient reported HRQoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire Myeloma Module (QLQ-MY20) instruments.
  • HRQoL was generally maintained during treatment with D-Id.

Safety

• At data cut-off, all enrolled patients were included in the safety population, with patients receiving a median of 16 cycles of D-Id (range: 1-45).
• The median relative dose intensities (RDIs) were 98.9%, 97.4%, and 92.9% for ixazomib, DARZALEX, and dexamethasone, respectively.¹⁹ 
• Safety data is summarized in Tables: Safety Data Summary and Most Common Any-Grade^a and Grade ≥3 TEAEs^b.

Phase 2 Study of D-Id as Second-Line Therapy in Patients With RRMM

DARIA (NCT03746652)⁹ was a prospective, open-label, multicenter, phase 2 study evaluating the effectiveness of D-Id as a second-line therapy in patients with RRMM who have received prior treatment with lenalidomide-based regimens. Terpos et al (2021)²⁰ presented the primary results of this study. Terpos et al (2024)¹⁰ presented the final efficacy and safety results of this study. The final outcomes have been summarized below.

Study Design/Methods

• Prospective, open-label, multicenter, phase 2 study.
• Key inclusion criteria: RRMM, measurable disease after 1 prior line of therapy with a lenalidomide-based regimen, Karnofsky performance status score ≥70, no previous anti-CD38 or ixazomib treatment, no treatment with CYP3A inducers within 14 days before cycle 1 day 1 (C1D1), no antimyeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment prior to C1D1, no allogeneic stem cell transplant or ASCT within 12 weeks before C1D1.
• Patients received 28-day cycles of the following induction treatment:
  • DARZALEX: 16 mg/kg IV from initiation to November 2020 and DARZALEX FASPRO 1800 mg SC thereafter QW during cycles 1-2, Q2W during cycles 3-6, and Q4W thereafter
  • Ixazomib: 4 mg PO on days 1, 8, and 15 of each cycle
  • Dexamethasone: 40 mg PO QW
• After induction, patients received 28-day cycles of the following maintenance treatment until PD or unacceptable toxicity:
  • DARZALEX: 16 mg/kg IV from initiation to November 2020 and DARZALEX FASPRO 1800 mg SC thereafter Q4W
  • Ixazomib: 4 mg PO on days 1, 8, and 15 of each cycle
• Primary endpoint: ORR
• Key secondary endpoints: Toxicity profile of D-Id, PFS, OS, DOR, TTP, time to next treatment (TtNT), changes in serum bone metabolism biomarkers

Results

Patient Characteristics

• Overall, 50 patients were included. The baseline patient and disease characteristics are summarized in Table: Baseline Patient and Disease Characteristics.
• The median follow-up was 23.4 months (range, 1.1-47.6).
• The median number of treatment cycles was 9 (range, 1-38).

Efficacy

• At the end of the study, the ORR was 64% (n=32)
  • One patient (2%) achieved CR, 16 (32%) achieved VGPR, and 15 (30%) achieved partial response (PR).
• The median PFS was 8.1 months (95% CI, 5.2-15.8), and the median OS was 39.2 months (95% CI, 17.4-39.3).
• The median DOR was 16.52 months (95% CI, 9.18-NR) and the median time to first response (≥PR) was 1.0 month (range, 0.9-17.6).
• The median TTP was 10.4 months (95% CI, 5.8-17.9) and the median TtNT was 14.5 months (95% CI, 9.1-39.3).
• Reasons for treatment discontinuation included PD (n=29, 58%), death (n=3, 6%), end of follow-up (n=13, 26%), AEs (n=2, 4%), and physician’s decision due to inadequate depth of response (n=3, 6%).
• Among the evaluated serum bone metabolism biomarkers, the changes from baseline in the levels of tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) at 6, 9, 12, 15, 18, 21, and 24 months and bone-specific alkaline phosphatase (bALP) at 12, 15, 18, 21, and 24 months and the level of osteocalcin (OC) at 3, 6, 9, 12, 15, 18, 21, and 24 months were statistically significant (P<0.05).

Safety

• At least 1 grade ≥3/4 AE was reported in 21 patients (42%).
  • The most frequent grade 3/4 AE was thrombocytopenia (18.0% [n=9]).
• At least 1 serious adverse event (SAE) was reported in 14 patients (28.0%).
  • The most frequent SAEs were lower respiratory tract infection (6.0% [n=3]) and acute kidney injury (4.0% [n=2]).
  • Four fatal infection-related SAEs were reported.
  • Five patients experienced ≥1 IRR; all were grade 2 and completely resolved, but 1 patient experienced grade 4 infusion-related dyspnea and bronchospasm that led to discontinuation.

Phase 2 Study of D-I in Frail Patients With RRMM

IDARA (IFM 2018-02, NCT03757221)¹¹ is an ongoing, open-label, multicenter, phase 2 study evaluating the efficacy and safety of D-I without dexamethasone in elderly patients with RRMM. Touzeau et al (2023)¹² presented the results of the IFM 2018-02 study at a data cutoff of January 19, 2023.

Study Design/Methods

• Key inclusion criteria: naïve to D-I, age >65 years, RRMM after 1 or 2 prior lines of therapy, frailty score ≥2 as per International Myeloma Working Group (IMWG) criteria, and ECOG PS score ≤2.
• Patients received 28-day cycles of the following treatment until PD:
  • DARZALEX: 16 mg/kg IV on days 1, 8, 15, and 22 during cycles 1-2; on days 1 and 15 during cycles 3-6; and on day 1 during cycles 7+
  • Ixazomib: 4 mg PO on days 1, 8, and 15 of each cycle
• Primary endpoint: ≥VGPR rate at 1 year
• Secondary endpoints: safety, ORR, PFS, and OS

Results

Patient Characteristics

• Overall, 55 patients were included. The baseline patient and disease characteristics are presented in Table: Key Baseline Patient and Disease Characteristics.
• The median duration of treatment was 22 months (range, 16-40).
• The median follow-up for OS was 22.5 months (range, 18.0-29.1) and PFS was 23 months (range, 19.6-29.1).

Efficacy

• The response outcomes are summarized in Table: Response Outcomes.
• The estimated OS at 27.9 months was 75%.
• The median PFS was 18.5 months (range, 11.0 to 29.9).
• Fourteen patients (25%) are ongoing treatment at a median follow-up of 23 months.

Safety

• Safety outcomes are summarized in Table: Safety Outcomes.
• Treatment was discontinued in 41 (75%) patients at a median treatment duration of 10 months (range, 0-31) (PD, n=24; AE, n=9; withdrawal, n=3; death, n=5).

Phase 2 Study of D-IPd in Patients with Early RRMM

180638 (NCT03590652) is an ongoing, multicenter, phase 2 study evaluating the ORR of patients with MM to D-IPd. Kumar et al (2023)¹⁴ reported the results of the interim analysis of this study.

Study Design/Methods

• Inclusion criteria: RRMM, ≥1 and ≤3 prior lines of therapy, ECOG PS 0-2, no prior progression on pomalidomide, no prior exposure to ixazomib or DARZALEX.
• Six patients received the following treatment during the safety run-in:
  • DARZALEX: 16 mg/kg IV
  • Pomalidomide: 4 mg PO on day 1 to 21/28
  • Ixazomib: 4 mg PO weekly
  • Dexamethasone: 20-40 mg PO weekly
• Forty patients received the following treatment at stage 1/2:
  • DARZALEX FASPRO: 1800 mg SC
  • Pomalidomide: 3 mg PO on day 1 to 21/28
  • Ixazomib: 3 mg PO weekly
  • Dexamethasone: 20-40 mg PO weekly
• Primary endpoint: ORR to D-IPd and 80% power to detect 20% improvement
• Key secondary endpoints: clinical benefit rate, DOR, PFS, OS, and rates of MRD negativity

Results

Patient Characteristics

• For key baseline patient and disease characteristics see Table: Key Baseline Patient and Disease Characteristics.

Efficacy

• The response outcomes are summarized in Table: Response Outcomes.
• The median time to response was 0.93 months.
• The median OS was 38.9 months (95% CI, ≥28.5) for all patients and 30.5 months (95% CI, ≥28.5) for the high-risk group.
• The median PFS was 22.4 months (95% CI, ≥9.49) for all patients and 22.4 months (95% CI, ≥7.64) for the high-risk group.
• The following correlative immunophenotypic changes were reported in patients treated with D-IPd:
  • Increased proliferating/acting cytotoxic T cells
  • Decrease in natural killer (NK) cells, with a general shift toward proliferating/activated NK and NK-T cells
  • Increase in monocytes
  • Decrease in plasmacytoid dendritic cells with a shift towards classical dendritic cells  

Safety

• Safety outcomes are summarized in Table: Safety Outcomes.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 09 January 2026.