SUMMARY

• DARZALEX for intravenous (IV) use + DARZALEX FASPRO for subcutaneous (SC) use are not approved by the regulatory agencies for use in combination with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) for the treatment of patients with multiple myeloma (MM). Janssen does not recommend the use of DARZALEX or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
• Mollee et al (2024)¹ conducted a prospective randomized, phase 2, open-label, multicenter study evaluating induction with DARZALEX in combination with CyBorD followed by DARZALEX maintenance in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The median progression-free survival (PFS) was 21.7 months overall, 25.8 months in the DARZALEX + CyBorD arm, and 16.8 months in the CyBorD arm. The best overall response rate (ORR) achieved was higher in the DARZALEX + CyBorD vs CyBorD arm (85.94% vs 64.91%; P=0.007). Minimal residual disease (MRD) negativity was achieved in 15.63% of patients in the DARZALEX + CyBorD arm and 5.26% of patients in the CyBorD arm (P=0.066) and did not affect the PFS (P=0.255). The median overall survival (OS) is estimated to be “not reached”
  (95% confidence interval [CI], 41.7-not available) in the DARZALEX + CyBorD arm and 58.7 months (95% CI, 47.0-not available) in the CyBorD arm (P=0.392). A total of 89% of patients from the DARZALEX + CyBorD arm vs 82% of patients from the CyBorD arm experienced ≥1 adverse event (AE). At 6 months after randomization, early deaths (n=6) were reported in 5 patients from the DARZALEX + CyBorD arm vs 1 patient from the CyBorD arm.
• Beksac et al (2021)² presented (at the 63rd American Society of Hematology [ASH] Annual Meeting and Exposition) the preliminary results of an ongoing, phase 2, singlearm, open-label, multicenter study evaluating the safety of DARZALEX in combination with CyBorD for the treatment of MM in patients with extramedullary involvement (N=22). At least 1 treatment-emergent adverse event (TEAE) was reported in 20 (90.9%) patients, and at least 1 serious TEAE was reported in 8 (36.4%) patients. At least 1 grade 3/4 TEAE was reported in 13 (59.1%) patients. Beksac et al (2023)³ reported the updated interim efficacy results of this study at a median follow-up of
  18.8 months. Overall, complete response (CR) or more was achieved by 17 (42.5%) patients (CR, 16 [40.0%]; stringent complete response [sCR], 1 [2.5%]). The ORR was 80.0% in the entire study population.
• LYRA is a phase 2, single-arm, open-label, multicenter study evaluating the safety and efficacy of DARZALEX when administered in combination with CyBorD for the treatment of MM in patients who have not received previous treatment or have relapsed after receiving only 1 line of treatment.^4-6
  • Yimer et al (2022)^6,7 reported the end-of-study analysis of LYRA. At the end of cycle 4, very good partial response or better (≥VGPR) was achieved by 57.1% patients in the relapsed multiple myeloma (RMM) arm and 44.2% patients in the NDMM arm. The median PFS was 21.7 months in the RMM arm and not reached (NR) in the NDMM arm (both in patients who received and did not receive transplant). The ORR was 86% in the RMM arm, 97% in the NDMM transplant arm, and 83% in the NDMM
    non-transplant arm. The most frequent any-grade TEAE was fatigue (68.6%).
    Grade 3/4 TEAEs occurred in 62.8% patients, with the most frequent being neutropenia (12.8%).
• Swan et al (2022)⁸ reported the results of a phase 1b clinical study evaluating the efficacy and safety of DARZALEX in combination with CyBorD in patients with NDMM eligible for autologous stem cell transplant (ASCT). Overall, 77.8% of patients achieved CR/sCR. The most common grade ≥3 AEs were lymphopenia, 16.7%; diarrhea, 11.1%; fatigue, 5.6%; and back pain, 11.1%.

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

Induction Therapy Using DARZALEX in Combination With CyBorD Followed by DARZALEX Maintenance

Mollee et al (2024)¹ is a prospective randomized, phase 2, openlabel, multicenter study evaluating induction with DARZALEX in combination with CyBorD followed by DARZALEX maintenance in transplant-ineligible patients with NDMM.

Study Design/Methods

• Patients were randomized 1:1 to receive nine 5-week cycles of either of the following treatment regimens:
  • CyBorD arm:
    • Bortezomib: 1.3 mg/m² SC on days 1, 8, 15, and 22.
    • Cyclophosphamide: 300 mg/m² orally (PO) on days 1, 8, 15, and 22.
    • Dexamethasone: 20 mg PO on days 1, 8, 15, and 22.
  • DARZALEX + CyBorD arm:  
    • DARZALEX: 16 mg/kg IV on days 1, 8, 15, and 22 of cycles 1 and 2; days 1 and 15 of cycles 3-6; and day 1 of cycles 7-9, followed by maintenance with 16 mg/kg IV Q4W until progressive disease (PD).
    • CyBorD as described above.
    • Patients received the below medications within 1 hour of DARZALEX administration to mitigate the risk of infusion-related reactions (IRRs).
      • Paracetamol: 1000 mg PO.
      • Diphenhydramine: 25-50 mg or equivalent PO or IV.
      • Dexamethasone: 20 mg PO.
      • Montelukast: 10 mg PO (optional).
• Primary endpoint: PFS.
• Secondary endpoints: ORR, MRD, OS, safety, toxicity, and global health status.

Results

Patient Characteristics

• The median duration of follow-up was 44.7 months.
• Overall, 121 patients were included (DARZALEX + CyBorD arm, n=64; CyBorD arm, n=57) in the study. The baseline patient and disease characteristics are summarized in Table: Baseline Characteristics.
• A total of 78%, 13%, and 8% of patients from the DARZALEX + CyBorD arm vs 61%, 26%, and 12% of patients from the CyBorD arm completed 9 cycles, ≤4 cycles, and
  5-8 cycles of induction, respectively.

Efficacy

• Median PFS was 21.7 months (95% CI, 17.7-26.3) overall, 25.8 months (95% CI,
  19.9-33.5) in the DARZALEX + CyBorD arm, and 16.8 months (95% CI, 15.3-21.7) in the CyBorD arm (hazard ratio [HR], 0.67; log rank test, P=0.066).
• Proportion of patients who were progression-free (DARZALEX + CyBorD vs CyBorD arm):
  • At 18 months: 68% vs 48%; P=0.0002.
  • At 24 months: 52% vs 36%; P=0.0001.
  • At 30 months: 41% vs 27%; P<0.0001.
• A significant difference in median PFS favoring the DARZALEX + CyBorD arm was reported for younger patients.
  • Younger patients (<75 years old): 29.8 months vs 16.3 months (95% CI,
    0.265-0.975; HR, 0.508; P=0.042).
  • Older patients (≥75 years old): 23.0 months vs 19.0 months (95% CI, 0.474-1.470; HR, 0.834; P=0.533).
• A difference in PFS favoring the DARZALEX + CyBorD arm was reported for patients with revised international staging system (R-ISS) stage II (95% CI, 0.308-0.851; HR, 0.512; P=0.010) and R-ISS stage III (95% CI, 0.040-1.024; HR, 0.202; P=0.053).
• The treatment response rates are summarized in Table: Treatment Responses.
• The follow-up period was not long enough to adequately assess OS differences between the arms. Hence, median OS was estimated to be NR (95% CI, 41.7-not available) in the DARZALEX + CyBorD arm and 58.7 months (95% CI, 47.0-not available) in the CyBorD arm (P=0.392).

Safety

• A total of 89% patients from the DARZALEX + CyBorD arm vs 82% patients from the CyBorD arm experienced ≥1 AE. See Table: Summary of AEs.
• The most common any-grade AEs that occurred in the DARZALEX + CyBorD arm vs CyBorD arm included pain (48% vs 47%), nausea and vomiting (25% vs 26%), diarrhea (25% vs 21%), peripheral neuropathy (28% vs 18%), fatigue and lethargy (20% vs 23%), lower limb edema (22% vs 16%), and upper respiratory tract infections (27% vs 11%).
• At 6 months after randomization, early deaths (n=6) were reported in 5 patients from the DARZALEX + CyBorD arm (PD, n=2; infection, n=3) vs 1 patient from the CyBorD arm (respiratory failure, n=1).

DARZALEX in Combination With CyBorD in Patients With MM With Extramedullary Involvement

Beksac et al (2021)² presented the preliminary results of an ongoing, phase 2, singlearm, open-label, multicenter study evaluating the safety of DARZALEX in combination with CyBorD for the treatment of MM in patients with extramedullary involvement. Beksac et al (2023)³ reported the updated interim efficacy results of this study at a median follow-up of 18.8 months.

Study Design/Methods

• Patients received the following regimen of DARZALEX in combination with CyBorD until PD or unacceptable toxicity unless refractory disease is detected by the end of cycle 3:
  • DARZALEX: 16 mg/kg IV weekly (QW) during cycles 1-2, every 2 weeks (Q2W) during cycles 36, and then every 4 weeks (Q4W) from cycle 7 onwards.
  • DARZALEX FASPRO: Starting July 2020, patients switched to receive DARZALEX FASPRO 1800 mg SC following the schedule described above.
  • Cyclophosphamide: 300 mg/m² PO or IV QW.
  • Bortezomib: 1.5 mg/m² SC QW.
  • Dexamethasone: 20 mg PO or IV on days 1, 2, 8, 9, 15, 16, 22, and 23.
• Inclusion criteria: Patients with newly diagnosed or 1st relapsed MM with extramedullary involvement who are nonrefractory to bortezomib-based regimens.
• Exclusion criteria: Bortezomib hypersensitivity, ASCT ≤12 weeks before day 1 of treatment cycle 1, and previous allogeneic stem cell transplant.
• Primary endpoint: ≥CR
• Key secondary endpoints: Duration of response (DOR), ORR, PFS, and safety.

Results - Preliminary Data

Patient Characteristics

• Patients (N=22) who initiated study treatment ≥3 months prior to the cutoff date were included in this analysis.
• The baseline patient and disease characteristics are summarized in Table: Baseline Characteristics.

Safety

• At least 1 TEAE was reported in 20 (90.9%) patients, and at least 1 serious TEAE was reported in 8 (36.4%) patients. At least 1 grade 3/4 TEAE was reported in 13 (59.1%) patients. See Table: Safety Outcomes.

• Treatment discontinuation was reported in 8 (36.4%) patients due to not reaching partial response (PR) after 3 cycles (n=3), PD (n=4), and death (n=1).

Beksac et al (2023)³ reported the updated interim efficacy results of this study at a median follow-up of 18.8 months.

Results - 18.8 Months Follow-Up

Patient Characteristics

• Overall, 40 patients were included. The baseline patient and disease characteristics are summarized in Table: Baseline Patient and Disease Characteristics.
• The median duration of follow-up was 18.8 months (range, 2.0-35.0).
• At data cut-off, 19 (47.5%) patients were on study treatment and 21 patients discontinued study treatment (PD, 13 [61.9%]; death, 3 [14.3%]; inadequate response after cycle 3, 3 [14.3%]; withdrawal, 1 [4.8%]; physician’s decision, 1 [4.8%]).
• At a median of 8.2 months (range, 5.9-10.2) after initiating study treatment, 10 (25%) patients received ASCT.
• Among the 38 evaluable patients, circulating tumor cells (CTC) were reported in 26 (68.4%) patients (paraosseous plasmacytoma, n=8; extramedullary plasmacytoma, n=16; both, n=2). See Table: Presence of CTC as per Disease Characteristics.
• The median level of CTC was 0.002% (range, 0-0.353).

Efficacy

• Hematologic treatment responses are summarized in Table: Hematologic Treatment Responses as per IMWG Criteria.
• Among first relapsed patients, 3 patients had complete metabolic response (CMR), of which 1 achieved prior to hematologic CR, 1 during the first assessment of extramedullary disease (EMD) response after CR, and for the 3rd patient, CR had not been achieved at the time of reporting.
• Among newly diagnosed patients, 11 patients achieved CMR, 2 achieved partial metabolic response, 1 had stable disease, and 1 had PD.
  • Among patients with CMR, 4 achieved CMR prior to hematologic CR, 6 achieved CMR at the first assessment of EMD response after CR, and 1 patient had not achieved CR at the time of reporting.
• The median PFS in different patient groups were as follows:
  • First relapsed: 15.3 months (95% CI, 0.95-NR).
  • Newly diagnosed: NR (95% CI, 7.2-NR).
  • 1-2 plasmacytomas: NR (95% CI, 10.2-NR).
  • 3+ plasmacytomas: 15.3 months (95% CI, 2.2-NR).
• The mean CTC levels in patients with ≥VGPR (n=29) was 0.04616 (standard deviation [SD], 0.09253) and that in patients with <VGPR (n=9) was 0.00408 (SD, 0.01072; P=0.0645).

DARZALEX in Combination with CyBorD in Patients with NDMM or RMM

LYRA (clinicaltrials.gov identifier: NCT02951819) is a phase 2, single-arm, open-label, multicenter study evaluating the safety and efficacy of DARZALEX when administered in combination with CyBorD for the treatment of MM in patients who have not received previous treatment or have relapsed after receiving only 1 line of treatment. Yimer et al (2019)⁴ published results with a median follow-up of 7.9 months for RMM and 8.8 months for NDMM. Rifkin et al (2019)⁹ presented updated safety and efficacy results at a median follow-up of 25.8 months for the NDMM arm and 26.6 months for the RMM arm. Yimer et al (2022)⁶ reported the end-of-study results at a median follow-up of 35.7 months for the NDMM arm and 35.3 months for the RMM arm.

Study Design/Methods

• Key eligibility criteria: Patients of ≥18 years of age with documented MM as per the International Myeloma Working Group (IMWG) criteria, ECOG performance status score of 0-2, and previously untreated NDMM or RMM with 1 prior line of therapy were eligible. Patients with RMM were included only if they achieved ≥PR with prior therapy before disease progression.⁴
• Patients refractory to a proteasome inhibitor (PI) or a combination of PI and immunomodulatory imide drug were excluded.⁴
• Patients received 4-8 cycles (28 days per cycle) of the following induction treatment⁴:
  • DARZALEX: 16 mg/kg IV.
    • Cycle 1: 8 mg/kg IV on days 1 and 2, followed by 16 mg/kg QW.
    • Cycle 2: QW.
    • Cycles 3-6: Q2W.
    • Cycles 7-8: Q4W.
  • Bortezomib: 1.5 mg/m² SC QW on days 1, 8, and 15 in all cycles.
  • Cyclophosphamide: 300 mg/m² PO QW on days 1, 8, 15, and 22 in all cycles.
  • Dexamethasone: 40 mg.
    • Cycle 1: 20 mg IV on days 1 and 2, followed by 40 mg QW.
    • Cycles 2-8: 40 mg IV/PO QW.
• After the induction phase, all patients received up to 12 cycles (28 days per cycle) of the following maintenance treatment⁴:
  • DARZALEX: 16 mg/kg IV Q4W.
  • Dexamethasone: 12 mg IV/PO on DARZALEX dosing days.
• Patients underwent high-dose therapy and ASCT at the discretion of the investigator after the induction phase.⁶
• Primary endpoint: ≥VGPR after 4 induction cycles.⁶
• Key secondary endpoints: ORR, time to ≥VGPR, time to ≥PR, PFS, OS, safety, and tolerability.⁶

Results

Patient Characteristics

• Overall, 101 patients were included (NDMM, n=87; RMM, n=14), of whom 100 received ≥1 dose of study treatment (NDMM, n=86; RMM, n=14).⁶
• The median follow-up duration was 35.7 months for the NDMM arm and 35.3 months for the RMM arm.⁶
• In total, 39 patients with NDMM and 1 patient with RMM received ASCT.⁶
• Demographic and baseline characteristics are summarized in Table: Patient Characteristics (LYRA).

Efficacy

• The median PFS was 21.7 months (95% CI, 6.8-not evaluable [NE]) in the RMM arm and NR in both the transplant and non-transplant NDMM arms.^6,7
  • The estimated 36-month PFS rates were 31.7% (95% CI, 5.6-63.4) in the RMM arm, 69.3% (95% CI, 43.0-85.3) in the NDMM transplant arm, and 72.6% (95% CI, 54.084.7) in the NDMM non-transplant arm.
• Median OS was NR. The estimated 36-month OS rates were 50% (95% CI, 22.9-72.2) in the RMM arm, 94.9% (95% CI, 81.0-98.7) in the NDMM transplant arm, and 84.3% (95% CI, 69.892.2) in the NDMM non-transplant arm.^6,7
• The median DOR was 20.7 months (95% CI, 5.9-NE) in the RMM arm and NR in both the transplant and non-transplant NDMM arms.^6,7
• For a summary of response rates over time in patients with RMM, transplant patients with NDMM, and non-transplant patients with NDMM, see Tables: Summary of Response Rates Over Time in Patients With RMM (LYRA), Summary of Response Rates Over Time in Transplant Patients With NDMM (LYRA), and Summary of Response Rates Over Time in Non-transplant Patients With NDMM (LYRA).

• In patients with NDMM achieving ≥CR vs those achieving ≤VGPR, estimated 36-month PFS rates were higher in both transplant (87.5% vs 51.2%) and non-transplant arms (100.0% vs 57.7%).⁶
• Among evaluable patients with NDMM and standard (n=52) vs high (n=31) cytogenetic risk⁶:
  • After induction, the rate of ≥VGPR was 61.5% vs 67.7% and the rate of ≥CR was 9.6% vs 16.1% for standard vs high risk, respectively.
  • By the end of the study, the rate of ≥VGPR was 75.0% vs 77.4% and the rate of ≥CR was 42.3% vs 29.0% for standard vs high risk, respectively.
• Among evaluable patients with NDMM and standard (n=53) vs high (n=31) cytogenetic risk⁶:
  • Median PFS was NR vs 33.1 months.
  • Estimated 36-month PFS rate was 87.5% vs 45.2% for standard vs high risk, respectively.

Safety

• In the RMM vs NDMM (both transplant and non-transplant) arm, grade 3/4 TEAEs occurred in 57.1% vs 62.8% of patients, serious TEAEs occurred in 35.7% vs 32.6% of patients, and cardiac TEAEs occurred in 0% vs 16.3% of patients. Grade 3 cardiac events (atrial fibrillation, n=4; atrial flutter, n=1) were reported in 4.7% (n=4) patients, all of which were serious and not related to study treatment.^6,7 See Table: Most Common TEAEs of Any Grade (≥25%) and Grade 3/4 (≥10%) in the Safety Analysis Set (LYRA).
• TEAEs leading to treatment discontinuation occurred in 1 patient in the RMM arm and 7 patients in the NDMM arm.^6,7
  • TEAEs leading to treatment discontinuation in the NDMM arm were anemia (n=2), atrial fibrillation, hip fracture, nephrotic syndrome, laryngeal edema, and rash (n=1 each).
  • In the NDMM arm, TEAEs leading to treatment discontinuation occurred in 5.6% (n=2) of patients who received transplants and 2.6% (n=1) of those who did not receive transplants.
• TEAEs leading to death was reported in 1 patient each in both the RMM and NDMM arms, all of which were unrelated to study treatment.^6,7
• In the NDMM arm, serious TEAEs occurred in 16.7% (n=6) of patients who received transplant and 23.1% (n=9) of patients who did not receive transplant.⁶
• The incidence of IRRs was 57.1% in the RMM arm and 55.8% in the NDMM arm.^6,7
  • In the RMM arm, all IRRs occurred during the induction phase and were of grade 1/2. No patient discontinued study treatment due to an IRR.
  • In the NDMM arm:
    • Grade 3 IRRs included anaphylactic reaction, chest discomfort, and hypertension (n=1 each). One patient reported laryngeal edema as a grade 4 IRR.
    • The majority of IRRs occurred during the first cycle of treatment.
      • Among patients who received transplants, 9 (25.0%) patients reported ≥1 IRR during the first maintenance cycle, with the majority being grade 1/2. Grade 3 (chest discomfort) and grade 4 (laryngeal edema) IRRs were reported in 1 patient each.
      • No IRRs were reported during maintenance treatment in patients who did not receive transplant.
    • One patient discontinued study treatment due to an IRR.
• TEAEs occurring in the maintenance phase are summarized in Tables: Most Common TEAEs of Any Grade (≥20%) and Grade 3/4 (≥5%) Occurring During the Maintenance Phase in the Safety Analysis Set (LYRA, RMM Arm) and Most Common TEAEs of Any Grade (≥20%) and Grade 3/4 (≥5%) Occurring During the Maintenance Phase in the Safety Analysis Set (LYRA, NDMM Arm).

DARZALEX in Combination with CyBorD in Patients with NDMM Eligible for ASCT

Swan et al (2022)⁸ reported the results of a phase 1b clinical study evaluating the efficacy and safety of DARZALEX in combination with CyBorD in patients with NDMM eligible for ASCT.

Study Design/Methods

• All patients received 4 cycles of the following induction treatment (28 days/cycle):
  • DARZALEX 16 mg/kg IV on days 1, 8, 15, and 22 during cycles 1 and 2 and on
    days 1 and 15 during cycles 3 and 4.
  • Cyclophosphamide: 150-300 mg/m² PO once a week (QW).
  • Bortezomib: 1.3-1.5 mg/m² SC QW.
  • Dexamethasone: 40 mg PO on days 1, 2, 8, 9, 15, 16, 22, and 23.
• After induction, patients underwent stem cell mobilization with cyclophosphamide, followed by melphalan therapy and ASCT.
• Patients received 2 cycles of consolidation therapy after ASCT following the same schedule as cycles 3 and 4 of induction and proceeded to maintenance with DARZALEX on day 1 of each cycle (28 day) until PD, unacceptable toxicity, or withdrawal of consent (maximum 2 years). Patients with high-risk disease also received bortezomib 1.3 mg/m² on days 1 and 15 of each maintenance cycle.
• Primary endpoints: Post-ASCT ≥CR rate, and the maximum tolerated dose of cyclophosphamide and bortezomib that can be safely delivered with DARZALEX.

Results

Patient Characteristics

• The baseline patient and disease characteristics are summarized in Table: Baseline Patient and Disease Characteristics.
• The median duration of follow-up was 2.9 years.
• Three patients discontinued the study before consolidation due to hepatic toxicity, PD, and death after ASCT (1 patient each).
• Fifteen patients proceeded to consolidation and maintenance therapy. The median duration of maintenance therapy was 23.7 months.

Transplant Characteristics

• Patients underwent stem cell mobilization using cyclophosphamide and
  granulocyte-colony stimulating factor (G-CSF) as per institutional protocol. Plerixafor was required in 4 patients.
• Successful harvesting was achieved in 93.8% of patients (15 of 16).
• The median number of harvested cluster of differentiation 34 (CD34)+ cells was 6.46×10⁶ cells/kg (range, 0.7-13.36).
• The median time to recovery of neutrophils to >0.5×10⁹ was 11 days (range, 9-13) and that of platelets to >20×10⁹ was 11 days (range, 7-14), after ASCT.
• One patient who had received intensive spinal radiotherapy failed to mobilize and proceeded directly to consolidation and maintenance.

Efficacy

• The ORR in the intent-to-treat (ITT) population was 94.1% after induction. Overall, 77.8% of patients achieved CR/sCR. The response outcomes are presented in Table: Response Outcomes (ITT Population).
• At the end of maintenance therapy, the PFS rate was 81.3% and the estimated 2-year OS rate was 88.9%.
• MRD (10^-5 threshold) was evaluated in 14 patients after induction, 13 after ASCT and consolidation each, and 10 at the end of treatment (EOT).
  • Sustained MRD-negativity (ie, from ASCT to EOT) was reported in 37.5% of patients.
  • Seven patients were MRD-negative after both ASCT and consolidation, of whom all those who were evaluable at EOT (n=6) remained MRD-negative. One patient was not able to undergo MRD assessment due to Coronavirus Disease 2019 (COVID-19), but remained in CR.
• Among patients with high-risk cytogenetics (n=4) and high-risk gene expression profile (GEP; n=1), 1 patient discontinued study due to deranged liver function, and 1 patient died after ASCT.
• One patient had PD during maintenance and 2 patients remained in MRD-negative CR/sCR at EOT.

Safety

• The most common AEs are summarized in Table: Most Common Adverse Events.
• Serious AEs occurred in 55.6% of patients (sepsis, influenza, urinary tract infection, and back pain; 2 cases each).
• No neuropathic pain or peripheral neuropathy related to study treatment was observed.

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 13 August 2024.