SUMMARY  

• Moreau et al (2020)¹ presented (at the 8^th Annual Meeting of the Society of Hematologic Oncology [SOHO]) safety and efficacy results of patients on DARZALEX for intravenous (IV) use that discontinued lenalidomide with or without dexamethasone (R±d) in the POLLUX² and MAIA³ studies.
• After ≥12 months of treatment, 71% (n=30) of patients discontinued R±d in POLLUX and 73% (n=53) in MAIA discontinued R±d. The most common reason for discontinuation were adverse event (AEs) in both studies (POLLUX: 90%, MAIA: 92%).¹ Please see Table: Reasons for Lenalidomide Discontinuation in POLLUX and MAIA.
• Treatment-emergent adverse events (TEAEs) were experienced in all patients that discontinued R±d in both the POLLUX and MAIA studies.¹ Please see Table: Most Common TEAEs in Patients that Discontinued Lenalidomide in POLLUX and MAIA.
  • POLLUX: Most common grade 3/4 TEAEs were neutropenia (64%), anemia (19%) fatigue (19%) and pneumonia (21%).¹
  • MAIA: Most common grade 3/4 TEAEs were neutropenia (58%), leukopenia (15%), lymphopenia (15%), and pneumonia (14%).¹
• At a median follow-up of:
  • POLLUX: 54.8 months, 91% of patients that discontinued R±d achieved very good partial response or better (≥VGPR) prior to discontinuing.¹
  • MAIA:  36.4 months, 90% of patients that discontinued R±d achieved ≥VGPR prior to discontinuing.¹
• POLLUX was a phase 3, randomized, open-label, multicenter study evaluating the safety and efficacy of lenalidomide and dexamethasone (Rd) and DARZALEX for intravenous (IV) use in combination with lenalidomide and dexamethasone (D-Rd) in patients with relapsed or refractory multiple myeloma (RRMM).²
• MAIA is an ongoing, phase 3, randomized, open-label, active-controlled, multicenter study evaluating the safety and efficacy of D-Rd and Rd in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients.^3,4
• For additional information on the POLLUX and MAIA studies,^2-4 please refer to the scientific responses as a result of your unsolicited request.

CLINICAL DATA

Moreau et al (2020)¹ presented safety and efficacy results of patients on DARZALEX that discontinued R±d in the POLLUX² and MAIA^3,4 studies. Results of this post-hoc subgroup analysis are summarized below.

Study Design/Methods

POLLUX:

• Patients with documented multiple myeloma (MM), measurable disease, and who received ≥1 prior line of therapy for MM with documented evidence of progressive disease (PD) as defined by the International Myeloma Working Group (IMWG) criteria on or after their last regimen were included.
• Exclusion criteria included: previous failure or discontinuation due to AEs on lenalidomide-based therapy, a neutrophil count ≤1.0 x 10⁹/L, hemoglobin ≤7.5 g/dL, platelets <75 x 10⁹/L, alanine or aspartate aminotransferase ≥2.5 x upper limit of normal (ULN), alkaline phosphatase ≥2.5 x ULN, bilirubin ≥1.5 x ULN, creatinine clearance <30 mL/minute
• Patients were randomized 1:1 to Rd (n=283) or D-Rd (n=286) and received 28-day cycles of:
  • Lenalidomide 25 mg orally (PO) on days 1 through 21 of each cycle and dexamethasone 40 mg weekly, or
  • Lenalidomide 25 mg PO on days 1 through 21 of each cycle, dexamethasone 20 mg prior to each DARZALEX infusion and 20 mg the day following each DARZALEX infusion, plus DARZALEX 16 mg/kg IV weekly for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter
  • Dexamethasone doses were decreased at physician discretion according to age and body weight.
• Primary endpoint: Progression-free survival (PFS)
• Key secondary endpoints: overall response rate (ORR), ≥VGPR, complete response or better (≥CR), minimal residual disease (MRD)-negativity rate, time to progression (TTP), progression-free survival on next line of therapy (PFS2), overall survival (OS)

MAIA:

• Key eligibility criteria: transplant ineligible NDMM, ECOG 0-2, creatinine clearance ≥30 mL/min
• Patients randomized 1:1 to Rd (n=369) or D-Rd (n=368) and received 28-day cycles of:
  • Lenalidomide: 25 mg PO daily on days 1-21 until PD (10 mg daily if creatinine clearance between 30-50 mL/min) and dexamethasone 40 mg PO weekly until PD (20 mg weekly in patients >75 years of age or with a body mass index [BMI] <18.5), or
  • Lenalidomide: 25 mg PO daily on days 1-21 until PD (10 mg daily if creatinine clearance between 30-50 mL/min) and dexamethasone 40 mg PO weekly until PD (20 mg weekly in patients >75 years of age or with a BMI <18.5), plus DARZALEX 16 mg/kg IV every week on cycles 1-2, every 2 weeks on cycles 3-6, and then every 4 weeks thereafter until PD
• Primary endpoint: PFS
• Key secondary endpoints: ≥VGPR, ORR, ≥CR, MRD-negativity rate, TTP and OS

Subgroup Analysis of R±d Discontinuation in POLLUX and MAIA

Results

Baseline Characteristics

• Baseline characteristics of those that discontinued R±d vs. those in the intent-to-treat (ITT) population are presented in the table: Baseline Patient Characteristics of Those that Discontinued R±d in POLLUX and MAIA.

Safety

In POLLUX, amongst patients that discontinued R±d:

• Median duration of study treatment was 52.0 (range, 6.5-60.6) months and the median time to R±d discontinuation was 18.8 (range 3-49) months.
• TEAEs were reported in all patients.
• TEAE leading to discontinuation of lenalidomide was reported in 79% (n=33).
  • ≥1 TEAE related to lenalidomide was 60% (n=25).
• Three grade 5 TEAEs were reported in POLLUX.
• Grade 3/4 TEAES were reported in 98% (n=41) in POLLUX.
• Most common grade 3/4 TEAEs were neutropenia (64%), pneumonia (21%), fatigue (19%), and anemia (19%).

In MAIA, amongst patients that discontinued R±d:

• Median duration of study treatment was 36.4 (range, 7.9-46.9) months and the median time to R±d discontinuation was 21.3 (range, 1-42) months.
• TEAEs were reported in all patients.
• TEAE leading to discontinuation of lenalidomide was reported in 82% (n=60).
  • ≥1 TEAE related to lenalidomide was 77% (n=56).
• No grade 5 TEAEs were reported in MAIA.
• Grade 3/4 TEAEs were reported in 97% (n=71) in MAIA.
• Most common grade 3/4 TEAEs were neutropenia (58%), leukopenia (15%), lymphopenia (15%), and pneumonia (14%).

• In an updated analysis of MAIA at a median follow up of 64.5 months, the rate of treatment discontinuation due TEAEs in the D-Rd vs Rd arm was 14.6% vs 23.8%.⁴
  • There were no TEAEs leading to discontinuation of lenalidomide specifically reported.

Efficacy

• For PFS rates, please refer to Tables: PFS at 12- and 24-month Landmark Analyses in MAIA, PFS at 12- and 24-month Landmark Analyses in POLLUX and PFS Rates in Patients that Discontinued Lenalidomide in POLLUX and MAIA.
• For response rates, please refer to Tables: Response Rates Prior to Discontinuation of R±d in Patients that Discontinued Lenalidomide in POLLUX at Median Follow-up of 54.8 months and Response Rates Prior to Discontinuation of R±d in Patients that Discontinued Lenalidomide in MAIA at Median Follow-up of 36.4 months.
• MRD-negativity rates (10^-5):¹
  • POLLUX: 48% (n=20) in those patients that discontinued R±d, 60% (n=18) in those that discontinued R±d after ≥12 months, and 33% (n=93) in D-Rd in the ITT population.
  • MAIA: 33% (n=24) in those patients that discontinued R±d, 38% (n=20) in those that discontinued R±d after ≥12 months, 29% (n=106) in D-Rd in the ITT population.

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 20 November 2024.