BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma

Abstract

The combination of clarithromycin, lenalidomide, and dexamethasone (BiRd) was evaluated as therapy for treatment-naive symptomatic multiple myeloma (MM), with overall response at 2 years of 90%. We reviewed the long-term follow-up of initial BiRd therapy. Seventy-two patients were given dexamethasone 40 mg weekly, clarithromycin 500 mg twice daily, and lenalidomide 25 mg daily on days 1 to 21 of a 28-day cycle. After a median follow-up of 6.6 years, overall response rates were 93%, with a very good partial response or better of 68%. Median progression-free survival was 49 months. Evaluation for the development of second primary malignancies (SPMs) was conducted, and no increase in incidence was noted in our cohort of patients who received frontline immunomodulatory therapy. BiRd remains a highly potent and safe regimen for frontline therapy in patients with MM without apparent increase in risk of SPMs. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

Figures

Figure 1

Survival curves. (A) OS. N = 69 patients, 21 deaths. Median OS not reached; 5-year OS = 75.2% (95% CI = 63.1%, 83.8%). (B) OS by transplant status. No transplant/continuous BiRD: 36 patients, 12 deaths, median OS = not reached; 5-year OS = 75.0% (95% CI = 57.5%, 86.1%). Transplant: 33 patients, 9 deaths, median OS = not reached; 5-year OS = 75.2% (95% CI = 56.4%, 86.7%). (C) OS by cytogenetics. Standard risk: 53 patients, 13 deaths, median OS = not reached; 5-year OS = 79.3% (95% CI = 65.7%, 87.9%). High risk: 10 patients, 5 deaths, median OS = 80 months; 5-year OS = 60.0% (95% CI = 25.3%, 82.7%). (D) PFS. N = 68 patients, 39 progressions. Median PFS = 52 months; 5-year PFS = 41.2% (95% CI = 28.9%, 53.1%). (E) PFS by transplant status: no transplant/continuous BiRD: 36 patients, 18 progressions, median PFS = 60 months; 5-year PFS = 43.4% (95% CI = 25.9%, 59.7%). Transplant: 32 patients, 21 progressions, median PFS = 47 months; 5-year PFS = 38.8% (95% CI = 22.1%, 55.2%). (F) PFS by cytogenetics. Standard risk: 53 patients, 29 progressions, median PFS = 64 months; 5-year PFS = 46.4% (95% CI = 32.2%, 59.4%). High risk: 10 patients, 6 progressions, median PFS = 49 months; 5-year PFS = 28.0% (95% CI = 4.4%, 59.7%). (G) EFS. N = 69 patients, 46 progressions, second malignancies, or deaths. Median EFS = 47 months; 5-year EFS = 34.2% (95% CI = 23.1%, 45.7%).