CPR, MPR, and Rd Produced Similar PFS and OS in Elderly Patients With Newly Diagnosed MM

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• Updated results from randomized, controlled phase III study[1]

Summary of Key Conclusions

• In elderly patients with newly diagnosed multiple myeloma (MM), similar efficacy seen with frontline cyclophosphamide/prednisone/lenalidomide (CPR); melphalan/prednisone/lenalidomide (MPR); and lenalidomide plus low-dose dexamethasone (Rd)

o 2-year PFS rate: 50% vs 54% vs 48%, respectively

o 2-year OS rate: 84% vs 81% vs 80%, respectively

o Response >= PR: 72% vs 73% vs 74%, respectively

• MPR had worse safety profile: significantly higher rates of grade 3/4 anemia, thrombocytopenia, and neutropenia vs CPR and Rd

• No difference in PFS or OS with maintenance lenalidomide alone vs lenalidomide plus prednisone

Background

• Combination therapy regimens with lenalidomide provide benefit for patients with newly diagnosed MM[2-4]

o Associated with high incidence of hematologic adverse events

• Current study designed to evaluate efficacy and safety of frontline CPR vs MPR vs RD and to compare maintenance with lenalidomide with or without prednisone in elderly patients with newly diagnosed MM not eligible for transplantation

Eligibility

• Main inclusion criteria

o Newly diagnosed MM

o Transplantation ineligible

o Elderly (65 years of age or older)

• Main exclusion criteria

o No previous systemic therapy (excluding radiotherapy, bisphosphonates, or short course steroids) for MM

o No major medical conditions or previous history of other malignancies

Baseline Characteristics

• Baseline characteristics generally balanced across treatment arms

• Median age: 73 years (more than one third older than 75 years of age)

Description of Current Analysis

• Primary endpoints: efficacy (PFS)

• Secondary endpoints: OS, ORR, TTP, duration of response, safety, prognosis and cytogenetic abnormalities

• Frontline median follow-up: 26 months

• Maintenance median follow-up: 17 months

Main Findings

• No significant efficacy differences between CPR, MPR, and Rd

o Median PFS

• CPR: 24 months (HR: 1.032; CI: 0.799-1.332; P = .81 vs Rd)
• MPR: 27 months (HR: 1.189; CI: 0.911-1.551; P = .20 vs Rd)
• Rd: 22 months
  

• Similar ORR across treatment arms (median cycles: 9 [range: 1-9])

• Significantly more grade 3/4 neutropenia, thrombocytopenia, and anemia with MPR

o Grade 3/4 neutropenia

• CPR: 28%
• MPR: 65%
• Rd: 25%

Other Outcomes

• No OS or PFS differences between CPR, MPR, or Rd in subpopulations

o Age (75 years of age or younger or older than 75 years)

o Frailty (fit, unfit, or frail)

o No chromosomal abnormalities

o Genetic abnormalities, including del(17), t(4;14), or t(14;16)

• Statistically significant difference in OS when comparing overall treatment in subpopulations

o Chromosomal abnormalities: none vs del(17), t(4;14), or t(14;16)

• HR: 1.716 (CI: 1.167-2.542; P = .006)

o Frailty: fit vs frail

• HR: 2.687 (CI: 1.796-4.022; P < .0001)

• No significant difference in PFS or OS with maintenance lenalidomide alone or in combination with prednisone

o Current follow-up of 17 months, longer follow-up needed for confirmation of long-term efficacy

References

1. Palumbo A, Magarotto V, Bringhen S, et al. A randomized phase 3 trial of melphalan-lenalidomide-prednisone (MPR) Or cyclophosphamide-prednisone-lenalidomide (CPR) vs lenalidomide plus dexamethasone (Rd) in elderly newly diagnosed multiple myeloma patients. Program and abstracts of the 55th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2013; New Orleans, Louisiana. Abstract 536.

2. Palumbo A, Hajek R, Delforge M, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012;366:1759-1769