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.)
