Early Normalization of Serum Free Light Chain Is Associated with Prolonged Time to Progression Following Bortezomib Pegylated Liposomal Doxorubicin Treatment of Relapsed/Refractory Multiple Myeloma.

Konference: 2007 49th ASH Annual Meeting - účast ČR

Kategorie: Mnohočetný myelom

Téma: Postery

Číslo abstraktu: 2735

Autoři: MD Robert Orlowski, PhD.; MD Heather J. Sutherland, PhD, FRACP; Prof. Dr. Joan Bladé, PhD; Prof. M.D. Jesús San Miguel, Ph.D.; prof. MUDr. Roman Hájek, CSc.; MD Arnon Nagler, MSc.; MD Pieter Sonneveld, PhD.; MD Andrew Spencer; MD Tadeusz Robak, PhD.; Mundle Suneel; Donghan Luo; Sen Hong Zhuang; Harousseau Jean-Luc

Multiple myeloma (MM), like other monoclonal gammopathies, frequently causes impairment of the / serum free light chain (sFLC) ratio. Based on a short serum half-life of FLC as compared to the complete immunoglobulin (hours versus days), early normalization of / could predict for response to treatment. As part of a randomized, controlled study, we examined the association between normalization of the / ratio after one or two 21-day cycles of treatment with bortezomib (B) pegylated liposomal doxorubicin (PLD) among patients with relapsed/refractory multiple myeloma. Patients with 1 prior therapy were randomized to receive PLD 30 mg/m2 on day 4 and B 1.3 mg/m2 on days 1, 4, 8, and 11, or B alone for up to eight 21-day cycles, or at least 2 cycles beyond complete response (CR) or optimal response, unless disease progression or unacceptable toxicities occurred (Orlowski, JCO 2007). / measurements were carried out prior to the start of therapy and at the end of each cycle through the entire study period using an immunoassay (Freelite, The Binding Sites, Birmingham, UK). Serial sFLC / measurements were available on sera from 487 patients with baseline values out of a total of 646 study patients. At baseline, 458/487 patients (94%) had an abnormal / ratio (<0.26 or >1.65). The percentage of patients with normal / ratio increased from 6% at baseline to 12% after cycle 1, 17% after cycle 2 and 23% by the end of the study. Among patients with a normal / ratio after cycle 1 (n=54), the median time to progression (TTP) was 345 days compared to 225 days in patients with abnormal ratios (n=395, p=0.0005, HR=0.47 favoring normalization). Following cycle 2, TTP was 325 days vs. 224 days (p0.001) in patients with normal (n=72) vs. abnormal (n=348) ratios, respectively. Additionally, patients with normalized sFLC ratios showed significantly higher overall response rates as compared to those with persistently abnormal ratios ( partial response [PR] 73% vs. 47%, p=0.001 following cycle 1, and 77% vs. 48%, p<0.0001 following cycle 2, respectively). Similarly, CR + very good PR rates were significantly higher among patients with normalized sFLC ratios after cycles 1 and 2 (p<0.0001 and p<0.001 respectively). As reported previously, both treatments, B + PLD and B alone, were well tolerated (Orlowski, JCO 2007). Normalization of the sFLC ratio as early as after cycle 1 of B + PLD, or B alone, was associated with a prolonged TTP and higher response rates. Additional analyses are undertaken to evaluate whether Freelite data: (a) predict treatment outcome earlier than electrophoresis, and (b) correlate with 24-hour urine M-protein.

Abstract #2735 appears in Blood, Volume 110, issue 11, November 16, 2007

Keywords: Doxil|Velcade|Randomized

Disclosure: Employment: Suneel Mundle and Sen Hong Zhuang are employees of Johnson Johnson. Consultancy: Joan Blad, Johnson Johnson; Jess San Miguel, Johnson Johnson, Celgene, and Pharmion; Pieter Sonneveld; Johnson Johnson. Ownership Interests:; Suneel Mundle and Sen Hong Zhuang own stock in Johnson Johnson. Research Funding: Joan Blad, Johnson Johnson; Tadeusz Robak, Johnson Johnson. Honoraria Information: Joan Blad, Johnson Johnson; Jess San Miguel, Johnson Johnson, Celgene, and Pharmion; Andrew Spencer, Johnson Johnson; Jean-Luc Harousseau, Millenium. Membership Information: Jess San Miguel, Johnson Johnson, Celgene, and Pharmion; Andrew Spencer, Johnson Johson; Jean-Luc Harousseau, Johnson Johnson and Millenium; Robert Orlowski, Johnson Johnson and Millennium; Heather Sutherland, Johnson Johnson.

Sunday, December 9, 2007 6:00 PM

Session Info: Poster Session: Myeloma: Relapsed and Refractory Multiple Myeloma (6:00 p.m.-8:00 p.m.)

Datum přednesení příspěvku: 9. 12. 2007