BiRD (Biaxin®/Revlimid®/Dexamethasone) Combination Therapy (Rx) Results in High Complete Remissions (CR) and Overall Responses in Myeloma (MM) with Poor Prognostic Features.

Revlimid® (R) or lenalidomide is the leading clinical compound in a new group of drugs called IMiD®s, which have immunomodulatory properties. In contrast with thalidomide (T) R has significantly less neurological toxicity. Several phase I and II trials with R showed promising results in relapsed/refractory MM. Our group demonstrated that Bi augments tumor mass reduction and improves responses in patients (pts) receiving low-dose T and/or D. We report the initial results of a phase II trial exploring the combination of Bi plus R plus D (BiRD) in newly diagnosed MM.

Methods: The trial is designed to accrue 35 pts. Thus far 28 pts have been accrued between Nov. 2004 and Aug. 2005 of which 22 pts (13 male and 9 female) are eligible for evaluation. R is given orally (po) at a dose of 25 mg daily on days 1–21 of a 28-day cycle. D is given po at a dose of 40 mg once weekly. Bi is given po at 500 mg twice daily. All pts also receive low dose aspirin (ASA)(81mg) once daily as thrombosis prophylaxis, prophylactic sulfamethoxazole/trimethoprim, and a proton pump inhibitor. Responses are defined according to the EBMTR. In addition, the category of near-CR (nCR) is defined as a CR with a positive immunofixation. A minimum of 2 cycles is required for response assessment; all pts are assessed on an intent-to-treat basis.

Results: Pt characteristics are as follows: median age of 62 years (range 36–77), hemoglobin of 11.4g/dL (range 7.2–15.1), platelets of 247k/uL (range 51–526), β2m of 4.0mg/L (range 0.8–5.1), CRP of 1.0mg/dL (range 0.3–8.4), creatinine of 1.3mg/dL (range 0.5–3.1), albumin of 3.6g/dL (range 2.3–4.9), and calcium of 8.9mg/dL (range 6.9–11.2). Conventional cytogenetics was normal in all pts; FISH abnormalities are as follows: trisomy 11 (2 pts), tetrasomy 11 (1 pt), del13q14(5 pts), t(4,14)(1pt), t(11,14)(2 pts). 52% of the pts are stage IIIa, 13% are stage IIIb, 35% are stage IIa. Responses are summarized in the table below. Of the 22 evaluable pts, 21(95%) have achieved an objective response (>PR) within 1–2 months of Rx with the remaining pt continues to respond. Nearly one third of pts have achieved either a CR(6/22) or a nCR(1/22-continuing on Rx). The remaining 14 pts(63%) achieved a PR. Of those pts who achieved a PR, 6/14 pts(43%) had >90% reduction in the initial paraprotein, while 12/14 pts(86%) had >75% decrement. 5 pts are now off study (3 pts in CR going to PBSCT and 2 due to toxicities). So far 15 pts have experienced grade ≥3 adverse events. These include, anemia(4.5%), neutropenia(4.5%), thrombocytopenia(4.5%), increased liver enzymes(4.5%), anxiety(4.5%), insomnia(9%), tremors(4.5%), hyperglycemia(4.5%), syncope(4.5%), Stevens Johnson’s(4.5%) and colonic perforation(4.5%). DVT occurred in 3(13.6%) patients, all off ASA, of which 2 (9%) had an associated PE, one of whom died. No grade 4 toxicities have been otherwise observed. Three pts have undergone successful stem cell harvest of which one has undergone transplantation with melphalan 200. Engraftment was successful by day 12.

Conclusions: BiRD is highly effective and safe in the initial Rx of MM. Stem cell harvest is not impaired after BiRD induction. Supported in part by the LLS SCOR grant and K23CA109260-01