Dr. Niesvizky discusses an analysis of 68 newly-diagnosed patients treated with Biaxin, Revlimid, and dexamethasone. The overall response rate was 90%, with 38% achieving CR/VGPR. Dose reductions were required in 11 of 58 patients because of myelosuppression). All but one of these patients had elevated baseline serum creatinine clearance, making it a viable marker for giving a reduced dose of Revlimid.
Lenalidomide Induced Myelosupression Is Potentially Associated with Renal Dysfunction in Treatment Nave Myeloma (MM) Patients Receiving BiRD (Biaxin/Revlimid/Dexamethasone) Combination Therapy (Rx). Session Type: Poster Session, Board #778-III
Ruben Niesvizky, D.S. Jayabalan, F. Zafar, P. Christos, R. Lent, R. Pearse, J. Tepler, S. Ely, T. Shore, J. Harpel, M. Schuster, K. Pekle, J.B. Jalbrzikowski, H.J. Cho, J. Leonard, M. Mazumdar, S. Chen-Kiang, M. Coleman Center of Excellence for Lymphoma Myeloma, Weill Medical College of Cornell University, NY, NY, USA
Lenalidomide or Revlimid has recently been approved for the treatment of relapsed or refractory MM. It has been demonstrated that Biaxin(Bi) augments tumor mass reduction and improves responses in patients (pts) receiving low-dose thalidomide and/or Dexamethosone (D). The results of a phase II trial exploring the combination of Bi, R D in newly diagnosed MM are reported here. The planned accrual target was met and additional patients accrued for correlative studies. The BiRD regimen consists of R 25 mg po daily on days 1-21 of a 28-day cycle. D 40 mg once weekly and Bi 500 mg po twice daily. All pts received low dose aspirin (ASA)(81mg) once daily as thrombosis prophylaxis, prophylactic sulfamethoxazole/ trimethoprim, and a proton pump inhibitor. PATIENTS: 58 pts[median follow-up 9 months (range 2-21)] have been accrued. Median age of 62.5 years (range 36-80), hemoglobin of 10.9 g/dL (range 7.2-15.1), platelets of 242 k/uL (range 51-526), B2M of 3mg/L (range 0.8 12.8), CRP of 0.56 mg/dL (range 0.12-14.2), creatinine (Cr) of 1.2 mg/dL (range 0.6-3.1), albumin of 3.55g/dL (range 2.3-4.9), and calcium of 9.3mg/dL (range 6.9 -11.2). 50% of the pts are stage IIIa, 7% are stage IIIb, 41.4% are stage Iia. According to ISS classification 28/58 are stage I (48%), 18/58 are stage II (31%) 12/58 are stage III (20%). RESULTS: This combination yielded a 95% overall response rate (EBMTR) by ITT with 38% of the pts achieving either a CR(16/58) or a nCR(6/58). Of the remaining 36 pts, 92% achieved a PR. Of those PR pts, 11/36 pts had >90% reduction in the initial paraprotein, while 12/36 pts had >75% decrease. All R dose reductions were due to myelosupression. R dose reduction scheme for myelosupression was defined as follows: Grade> 3 Neutropenia: Level -1: 25 mg po daily + G-CSF. Level -2 : 15 mg po daily and Level -3: 10 mg po daily. Thrombocytopenia: Level -2 : 15 mg po daily. Level -3: 10 mg po daily. 18% of the pts required at least one dose reduction. Of these patients, 6% required further dose reductions to level 2, and 2 patients were reduced to level 3. Mean time to R dose reduction level 1 was 65.1 days (range 15 to 142), to level 2 was 113 days (range 35 to 166) and to level 3 was 170 days (range 95 to 244). Baseline Cr level correlated with R dose reductions. Of the 11 patients who were dose-reduced, 1 had a baseline serum Cr level of 1.4 mg/dL, while the rest had a baseline serum Cr level >1.4 mg/dL (p<0.0001). Using baseline Cr level as a continuous variable in a Cox proportional hazards regression model results in a hazard ratio of 6.4 (95% CI = 2.1, 19.1), p=0.0009. This indicates a 6.4-fold increased likelihood of a dose reduction for each 1-unit increase in baseline serum creatinine level. Similarly, a Cr clearance (Cl) of 40, was associated with R dose-reductions (KM log-rank analysis 40 (n=12) versus >40 (p=0.0014). Other toxicities included PE (4%), DVT (9%), AMI (2%), and sudden death (2%). Other non-hematological toxicities included myopathy (6%), diverticular abscess (10%), hand tremor, weakness and hyperglycemia. Conclusions: BiRD is highly effective and safe in the initial Rx of MM. Myelosuppression renal dysfunction potentiated the need for R dose reduction. Supported in part by the LLS SCOR grant and K23CA109260-01.
Abstract #3549 appears in Blood, Volume 108, issue 11, November 16, 2006